Research

16 pages, 3665 KiB

Open AccessArticle

Identification of Biological Functions and Prognostic Value of NNMT in Oral Squamous Cell Carcinoma

by Weixian Zhang, Yue Jing, Shuai Wang, Yan Wu, Yawei Sun, Jia Zhuang, Xiaofeng Huang, Sheng Chen, Xiaoxin Zhang, Yuxian Song, Qingang Hu and Yanhong Ni

Biomolecules 2022, 12(10), 1487; https://doi.org/10.3390/biom12101487 - 15 Oct 2022

Cited by 3 | Viewed by 1687

Abstract

Background: Nicotinamide N-methyltransferase (NNMT) is a metabolic enzyme that catalyzes the methylation of nicotinamide (NAM) to generate 1-methyl nicotinamide (MNAM). Although previous studies have shown that NNMT is frequently dysregulated to promote the onset and progression of many malignancies, its expression profile, prognostic [...] Read more.

Background: Nicotinamide N-methyltransferase (NNMT) is a metabolic enzyme that catalyzes the methylation of nicotinamide (NAM) to generate 1-methyl nicotinamide (MNAM). Although previous studies have shown that NNMT is frequently dysregulated to promote the onset and progression of many malignancies, its expression profile, prognostic value and function in oral squamous cell carcinoma (OSCC) are still unknown. Methods: We used untargeted metabolomics based on mass spectrometry to analyze potential metabolite differences between tumors and matched adjacent normal tissues in 40 OSCC patients. Immunohistochemistry (IHC) was used to analyze the NNMT expression profile in OSCC, and the diagnostic and prognostic values of NNMT were evaluated. Next, qPCR and Western blot were used to compare the expression of NNMT in five OSCC cell lines. Stable transfected cell lines were constructed, and functional experiments were carried out to elucidate the effects of NNMT on the proliferation and migration of OSCC cells. Finally, gene set enrichment analysis (GSEA) was performed using The Cancer Genome Atlas (TCGA) data to investigate the potential functional mechanisms of NNMT in OSCC. Results: We found that the nicotinamide metabolic pathway was abnormally activated in OSCC tumor tissues compared with normal tissues. NNMT was expressed ubiquitously in tumor cells (TCs) and fibroblast-like cells (FLCs) but was absent in tumor-infiltrating lymphocytes (TILs). OSCC patients with highly expressed NNMT in TCs had higher risk of lymph node metastasis and showed a worse pattern of invasion (POI). Moreover, patients with highly expressed NNMT were also susceptible to postoperative recurrence. Highly expressed NNMT can independently predict shorter disease-free survival and recurrence-free survival. Functionally, we demonstrated that the ectopic expression of NNMT promoted OSCC tumor cell proliferation and migration in vitro. Conversely, silencing exerted significantly opposite effects in vitro. In addition, GSEA showed that highly expressed NNMT was mainly enriched in the epithelial–mesenchymal transformation (EMT) pathway, which displayed a significant positive correlation with the six classic EMT markers. Conclusions: Our study uncovered that NNMT may be a critical regulator of EMT in OSCC and may serve as a prognostic biomarker for OSCC patients. These findings might provide novel insights for future research in NNMT-targeted OSCC metastasis and recurrence therapy. Full article

(This article belongs to the Special Issue Biomolecules and Biomarkers in Head and Neck Medicine)

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9 pages, 759 KiB

Open AccessEditor’s ChoiceArticle

Plasma P-Tau181 for the Discrimination of Alzheimer’s Disease from Other Primary Dementing and/or Movement Disorders

by John S. Tzartos, Fotini Boufidou, Christos Stergiou, Jens Kuhle, Eline Willemse, Lina Palaiodimou, Ioanna Tsantzali, Eleni Sideri, Anastasios Bonakis, Sotirios Giannopoulos, Konstantinos I. Voumvourakis, Georgios Tsivgoulis, Socrates J. Tzartos, Elisabeth Kapaki and George P. Paraskevas

Biomolecules 2022, 12(8), 1099; https://doi.org/10.3390/biom12081099 - 10 Aug 2022

Cited by 3 | Viewed by 1790

Abstract

Blood phospho-tau181 may offer a useful biomarker for Alzheimer’s disease. However, the use of either serum or plasma phospho-tau181 and their diagnostic value are currently under intense investigation. In a pilot study, we measured both serum and plasma phospho-tau181 (pT181-Tau) by single molecule [...] Read more.

Blood phospho-tau181 may offer a useful biomarker for Alzheimer’s disease. However, the use of either serum or plasma phospho-tau181 and their diagnostic value are currently under intense investigation. In a pilot study, we measured both serum and plasma phospho-tau181 (pT181-Tau) by single molecule array (Simoa) in a group of patients with Alzheimer’s disease and a mixed group of patients with other primary dementing and/or movement disorders. Classical cerebrospinal fluid biomarkers were also measured. Plasma (but not serum) pT181-Tau showed a significant increase in Alzheimer’s disease and correlated significantly with cerebrospinal fluid amyloid and pT181-Tau. Receiver operating curve analysis revealed a significant discrimination of Alzheimer’s from non-Alzheimer’s disease patients, with an area under the curve of 0.83 and an excellent sensitivity but a moderate specificity. Plasma pT181-Tau is not an established diagnostic biomarker for Alzheimer’s disease, but it could become one in the future, or it may serve as a screening tool for specific cases of patients or presymptomatic subjects. Full article

(This article belongs to the Special Issue Biomolecules and Biomarkers in Head and Neck Medicine)

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15 pages, 5195 KiB

Open AccessArticle

Expression of Tumor Suppressor SFRP1 Predicts Biological Behaviors and Prognosis: A Potential Target for Oral Squamous Cell Carcinoma

by Chun Chen, Yifei Zhang, Yupeng Liu, Lei Hang and Jun Yang

Biomolecules 2022, 12(8), 1034; https://doi.org/10.3390/biom12081034 - 27 Jul 2022

Cited by 4 | Viewed by 1690

Abstract

Background: Genomic instability is implicated in the initiation and progression of oral squamous cell carcinoma (OSCC). Tumor suppressor Secreted Frizzled-Related Protein 1 (SFRP1) may participate in the aberrant evolution of OSCC, the intrinsic molecular mechanisms of which may provide effective therapeutic targets. Methods: [...] Read more.

Background: Genomic instability is implicated in the initiation and progression of oral squamous cell carcinoma (OSCC). Tumor suppressor Secreted Frizzled-Related Protein 1 (SFRP1) may participate in the aberrant evolution of OSCC, the intrinsic molecular mechanisms of which may provide effective therapeutic targets. Methods: A bioinformatics analysis was carried out on a publicly available database using R language to map the prognostic value, immune infiltration and enrichment of SFRP1 expression. Subsequently, in vitro experiments were conducted to unveil the biological function of SFRP1. Results: SFRP1 was found to be ubiquitously lowly expressed in OSCC using a Wilcoxon rank-sum test. Univariate analysis confirmed that those patients characterized by a low SFRP1 expression were significantly associated with advanced T-stage, clinical stage and poor mortality (p < 0.05). Furthermore, SFRP1 displayed a positive performance in tumor immune infiltration, especially in mast cells. Functional annotations indicated that highly expressed SFRP1 was associated with membrane potential and passive transmembrane transporter activity and it was mainly enriched in calcium pathway and neuroactive ligand–receptor interaction. In vitro, the overexpression of SFRP1 inhibited its proliferation, migration, and invasion and resulted in G0+G1 phase arrest within Cal27 cells (p < 0.05). Conclusions: The bioinformation data suggest that SFRP1 expression provides an insight into the risk and prognostic stratification in OSCC. SFRP1 was validated as a potential biomarker with anticarcinogenic behaviors for use in targeted therapy. Full article

(This article belongs to the Special Issue Biomolecules and Biomarkers in Head and Neck Medicine)

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16 pages, 891 KiB

Open AccessArticle

The Role of ApoE Serum Levels and ApoE Gene Polymorphisms in Patients with Laryngeal Squamous Cell Carcinoma

by Rasa Liutkeviciene, Justina Auzelyte, Vykintas Liutkevicius, Alvita Vilkeviciute, Greta Gedvilaite, Paulius Vaiciulis and Virgilijus Uloza

Biomolecules 2022, 12(8), 1013; https://doi.org/10.3390/biom12081013 - 22 Jul 2022

Viewed by 1657

Abstract

Recent studies have revealed that the inflammatory ApoE effect may play a significant role in various cancer development. However, this effect has still not been analyzed in patients with laryngeal squamous cell carcinoma (LSCC). In the present study, we evaluated two single nucleotide [...] Read more.

Recent studies have revealed that the inflammatory ApoE effect may play a significant role in various cancer development. However, this effect has still not been analyzed in patients with laryngeal squamous cell carcinoma (LSCC). In the present study, we evaluated two single nucleotide polymorphisms (SNPs) of ApoE (rs7412 and rs429358) and determined their associations with LSCC development and the LSCC patients’ five-year survival rate. Additionally, we analyzed serum ApoE levels using an enzyme-linked immunosorbent assay. A total of 602 subjects (291 histologically verified LSCC patients and 311 healthy controls) were involved in this study. The genotyping was carried out using the real-time PCR. We revealed that ApoE ε3/ε3 was associated with a 1.7-fold higher probability of developing LSCC (p = 0.001), with 1.7-fold increased odds of developing LSCC without metastasis to the lymph nodes (p = 0.002) and with a 2.0-fold increased odds of developing well-differentiated LSCC (p = 0.008), as well as 1.6-fold increased odds of developing poorly differentiated LSCC development (p = 0.012). The ApoE ε2/ε4 and ε3/ε4 genotypes were associated with a 2.9-fold and 1.5-fold decrease in the likelihood of developing LSCC (p = 0.042; p = 0.037, respectively). ApoE ε3/ε4 was found associated with a 2.4-fold decreased likelihood of developing well-differentiated LSCC (p = 0.013). Conclusion: ApoE ε2/ε4 and ε3/ε4 were found to play a protective role in LSCC development, while ApoE ε3/ε3 may have a risk position in LSCC development. Full article

(This article belongs to the Special Issue Biomolecules and Biomarkers in Head and Neck Medicine)

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10 pages, 2761 KiB

Open AccessArticle

Expression of Matrix Metalloproteinases 7 and 9, Desmin, Alpha-Smooth Muscle Actin and Caldesmon, in Odontogenic Keratocyst Associated with NBCCS, Recurrent and Sporadic Keratocysts

by Carla Loreto, Alessandro Polizzi, Veronica Filetti, Giuseppe Pannone, Jean Nunes Dos Santos, Pietro Venezia, Rosalia Leonardi and Gaetano Isola

Biomolecules 2022, 12(6), 775; https://doi.org/10.3390/biom12060775 - 02 Jun 2022

Cited by 4 | Viewed by 1869

Abstract

Nevoid basal cell carcinoma syndrome (NBCCS) associated odontogenic keratocysts (OKCs) show more aggressive behavior and it has a higher frequency of relapse than non-syndromic OKCs. Stromal myofibroblasts (MFs), characterized by α-smooth muscle actin (αSMA), desmin and caldesmon expression, and metalloproteinases (MMPs) have an [...] Read more.

Nevoid basal cell carcinoma syndrome (NBCCS) associated odontogenic keratocysts (OKCs) show more aggressive behavior and it has a higher frequency of relapse than non-syndromic OKCs. Stromal myofibroblasts (MFs), characterized by α-smooth muscle actin (αSMA), desmin and caldesmon expression, and metalloproteinases (MMPs) have an essential role in the remodeling of the extracellular matrix (ECM). The aim of the study is to analyze the immunohistochemical expression of MMP-7, MMP-9, αSMA and other new markers in the study of OKCs MFs such as desmin and caldesmon in NBCCS-associated OKCs compared to recurrent and sporadic keratocysts. Fourty 40 patients (23 M and 17 F) underwent surgery to remove the OKCs. The histological sections in paraffin were incubated with markers antibodies and a semi-quantitative score was used to evaluate the immunoreactivity. Densitometric analysis showed a very significantly increased expression of αSMA, caldesmon, MMP-7 and MMP-9 in NBCCS-OKCs compared to non-syndromic OKCs (p < 0.001). However, desmin showed a not significant increased expression in non-syndromic OKC compared to NBCCS-OKCs specimens in which desmin was slightly or not at all expressed. NBCSS-OKCs showed a greater distribution of MFs compared to the other OKCs subtypes. Further studies will be needed to evaluate whether the different expressions of these markers can be correlated to a different clinical behavior. Full article

(This article belongs to the Special Issue Biomolecules and Biomarkers in Head and Neck Medicine)

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13 pages, 2489 KiB

Open AccessArticle

Transcriptomic Biomarker Signatures for Discrimination of Oral Cancer Surgical Margins

by Simon A. Fox, Michael Vacher and Camile S. Farah

Biomolecules 2022, 12(3), 464; https://doi.org/10.3390/biom12030464 - 17 Mar 2022

Cited by 7 | Viewed by 2523

Abstract

Relapse after surgery for oral squamous cell carcinoma (OSCC) contributes significantly to morbidity, mortality and poor outcomes. The current histopathological diagnostic techniques are insufficiently sensitive for the detection of oral cancer and minimal residual disease in surgical margins. We used whole-transcriptome gene expression [...] Read more.

Relapse after surgery for oral squamous cell carcinoma (OSCC) contributes significantly to morbidity, mortality and poor outcomes. The current histopathological diagnostic techniques are insufficiently sensitive for the detection of oral cancer and minimal residual disease in surgical margins. We used whole-transcriptome gene expression and small noncoding RNA profiles from tumour, close margin and distant margin biopsies from 18 patients undergoing surgical resection for OSCC. By applying multivariate regression algorithms (sPLS-DA) suitable for higher dimension data, we objectively identified biomarker signatures for tumour and marginal tissue zones. We were able to define molecular signatures that discriminated tumours from the marginal zones and between the close and distant margins. These signatures included genes not previously associated with OSCC, such as MAMDC2, SYNPO2 and ARMH4. For discrimination of the normal and tumour sampling zones, we were able to derive an effective gene-based classifying model for molecular abnormality based on a panel of eight genes (MMP1, MMP12, MYO1B, TNFRSF12A, WDR66, LAMC2, SLC16A1 and PLAU). We demonstrated the classification performance of these gene signatures in an independent validation dataset of OSCC tumour and marginal gene expression profiles. These biomarker signatures may contribute to the earlier detection of tumour cells and complement existing surgical and histopathological techniques used to determine clear surgical margins. Full article

(This article belongs to the Special Issue Biomolecules and Biomarkers in Head and Neck Medicine)

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12 pages, 3637 KiB

Open AccessArticle

TLR4 Expression in Ex-Lichenoid Lesions—Oral Squamous Cell Carcinomas and Its Surrounding Epithelium: The Role of Tumor Inflammatory Microenvironment

by Fernanda Visioli, Julia Silveira Nunes, Maria Carmela Pedicillo, Rosalia Leonardi, Angela Santoro, Gian Franco Zannoni, Gabriella Aquino, Margherita Cerrone, Monica Cantile, Nunzia Simona Losito, Vito Rodolico, Giuseppina Campisi, Giuseppe Colella, Ilenia Sara De Stefano, Maria Antonietta Ramunno, Cristina Pizzulli, Marco Visconti, Lorenzo Lo Muzio and Giuseppe Pannone

Biomolecules 2022, 12(3), 385; https://doi.org/10.3390/biom12030385 - 28 Feb 2022

Cited by 1 | Viewed by 2116

Abstract

Toll-like receptors (TLRs) regulate innate and adaptive immune responses. Moreover, TLRs can induce a pro-survival and pro-proliferation response in tumor cells. This study aims to investigate the expression of TLR4 in the epithelium surrounding oral squamous cell carcinomas (OSCC) in relation to its [...] Read more.

Toll-like receptors (TLRs) regulate innate and adaptive immune responses. Moreover, TLRs can induce a pro-survival and pro-proliferation response in tumor cells. This study aims to investigate the expression of TLR4 in the epithelium surrounding oral squamous cell carcinomas (OSCC) in relation to its inflammatory microenvironment. This study included 150 human samples: 30 normal oral control (NOC), 38 non-lichenoid epithelium surrounding OSCC (NLE-OSCC), 28 lichenoid epithelium surrounding OSCC (LE-OSCC), 30 OSCC ex-non oral lichenoid lesion (OSCC Ex-NOLL), and 24 OSCC ex-oral lichenoid lesion (OSCC Ex-OLL). TLR4 expression was investigated by immunohistochemistry and the percentage of positive cells was quantified. In addition, a semiquantitative analysis of staining intensity was performed. Immunohistochemical analysis revealed that TLR4 is strongly upregulated in LE-OSCC as compared to normal control epithelium and NLE-OSCC. TLR4 expression was associated with the inflammatory environment, since the percentage of positive cells increases from NOC and NLE-OSCC to LE-OSCC, reaching the highest value in OSCC Ex–OLL. TLR4 was detected in the basal third of the epithelium in NLE-OSCC, while in LE-OSCC, TLR4 expression reached the intermediate layer. These results demonstrated that an inflammatory microenvironment can upregulate TLR4, which may boost tumor development. Full article

(This article belongs to the Special Issue Biomolecules and Biomarkers in Head and Neck Medicine)

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24 pages, 8876 KiB

Open AccessArticle

LPS Administration Impacts Glial Immune Programs by Alternative Splicing

by Vladimir N. Babenko, Galina T. Shishkina, Dmitriy A. Lanshakov, Ekaterina V. Sukhareva and Nikolay N. Dygalo

Biomolecules 2022, 12(2), 277; https://doi.org/10.3390/biom12020277 - 08 Feb 2022

Cited by 4 | Viewed by 1993

Abstract

We performed transcriptome analysis in the hippocampus 24 h after lipopolysaccharide (LPS) administration. We observed glial-specific genes, comprised of two-thirds of all differentially expressed genes (DEGs). We found microglial DEGs that were the most numerous in LPS group. On the contrary, differential alternative [...] Read more.

We performed transcriptome analysis in the hippocampus 24 h after lipopolysaccharide (LPS) administration. We observed glial-specific genes, comprised of two-thirds of all differentially expressed genes (DEGs). We found microglial DEGs that were the most numerous in LPS group. On the contrary, differential alternative splicing (DAS) analysis revealed the most numerous DAS events in astrocytes. Besides, we observed distinct major isoform switching in the Ptbp1 gene, with skipping of exon 8 in LPS group. Ptbp1 usually considered a pluripotency sustaining agent in brain embryonic development, according to the previous studies. Analyzing the splicing tune-up upon LPS exposure, we came to a supposition that the short Ptbp1 isoform de-represses immune-specific response by Ptbp1 adjusted splicing architecture. Additionally, the Ptbp3 (NOD1) immune-specific splicing factor has apparently been de-repressed by the Ptbp1 short isoform in glial cells. Notably, both the Ptbp1 and Ptbp3 genes express primarily in microglial/endothelial brain cells. We also report immune-related genes, altering their major isoforms upon LPS exposure. The results revealed immune modulating role of alternative splicing in brain. Full article

(This article belongs to the Special Issue Biomolecules and Biomarkers in Head and Neck Medicine)

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13 pages, 5245 KiB

Open AccessArticle

Identification and Validation of PLOD2 as an Adverse Prognostic Biomarker for Oral Squamous Cell Carcinoma

by Yawei Sun, Shuai Wang, Xingwei Zhang, Zhuhao Wu, Zihui Li, Zhuang Ding, Xiaofeng Huang, Sheng Chen, Yue Jing, Xiaoxin Zhang, Liang Ding, Yuxian Song, Guowen Sun and Yanhong Ni

Biomolecules 2021, 11(12), 1842; https://doi.org/10.3390/biom11121842 - 07 Dec 2021

Cited by 10 | Viewed by 2940

Abstract

Background: Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a key enzyme that catalyzes the hydroxylation of lysine, plays a crucial role in the progression of several solid tumors. However, its spatial expression profile and prognostic significance in oral squamous cell carcinoma (OSCC) have not been [...] Read more.

Background: Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a key enzyme that catalyzes the hydroxylation of lysine, plays a crucial role in the progression of several solid tumors. However, its spatial expression profile and prognostic significance in oral squamous cell carcinoma (OSCC) have not been revealed. Materials: Mass spectrometry was used to explore amino acid perturbations between OSCC tumor tissues and paired normal tissues of 28 patients. Then, PLOD2 mRNA and protein levels were assessed using several public databases and 18 pairs of OSCC patients’ tissues. Additionally, PLOD2 spatial expression profiles were investigated in 100 OSCC patients by immunohistochemistry and its diagnostic and prognostic values were also evaluated. Lastly, gene set enrichment analysis (GSEA) was used to investigate the potential functions of PLOD2 in OSCC. Results: Lysine was significantly elevated in OSCC tissues and could effectively distinguish tumor from normal tissues (AUC = 0.859, p = 0.0035). PLOD2 mRNA and protein levels were highly increased in tumor tissues of head and neck squamous cell carcinoma (HNSCC) (p < 0.001) and OSCC compared with those in nontumor tissues (p < 0.001). Histopathologically, PLOD2 was ubiquitously expressed in tumor cells (TCs) and fibroblast-like cells (FLCs) of OSCC patients but absent in tumor-infiltrating lymphocytes (TILs). Patients with highly expressed PLOD2 in TCs (PLOD2^TCs) and FLCs (PLOD2^FLCs) showed poor differentiation, a worse pattern of invasion (WPOI) and more lymph node metastasis (LNM), contributing to higher postoperative metastasis risk and poor survival time. However, PLOD2^FLCs rather than PLOD2^TCs was an independent risk factor for survival outcomes in OSCC patients. Molecularly, GSEA demonstrated highly expressed PLOD2 was mainly enriched in epithelial–mesenchymal transformation (EMT), TGF-beta signaling and hypoxia pathway, which are associated with poor clinical outcomes of OSCC patients. Conclusions: PLOD2 was a poor prognostic biomarker for OSCC patients and may affect the metastasis of OSCC through EMT pathway. These findings might shed novel sights for future research in PLOD2 targeted OSCC therapy. Full article

(This article belongs to the Special Issue Biomolecules and Biomarkers in Head and Neck Medicine)

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13 pages, 3449 KiB

Open AccessArticle

Immunocytometric Analysis of Oral Pemphigus vulgaris Patients after Treatment with Rituximab as Adjuvant

by Giulio Fortuna, Elena Calabria, Massimo Aria, Amerigo Giudice and Michele Davide Mignogna

Biomolecules 2021, 11(11), 1634; https://doi.org/10.3390/biom11111634 - 04 Nov 2021

Viewed by 1793

Abstract

Background: B-cell depletion therapy was demonstrated to be a valid and safe alternative as an adjuvant in oral-pharyngeal pemphigus vulgaris (OPV) patients. We aimed to assess its effects on anti-desmoglein (Dsg) 1 and 3 and leukocytes subsets profile in these patients’ population. Methods [...] Read more.

Background: B-cell depletion therapy was demonstrated to be a valid and safe alternative as an adjuvant in oral-pharyngeal pemphigus vulgaris (OPV) patients. We aimed to assess its effects on anti-desmoglein (Dsg) 1 and 3 and leukocytes subsets profile in these patients’ population. Methods and Materials: We evaluated the immunologic profile of 10 OPV patients treated with RTX as adjuvant by using the ELISA testing for anti-Dsg-1 and -3 titers and the immunophenotyping for B and T-cell lymphocyte subpopulations and compared them with the PDAI score for clinical remission. Results: A significant difference in medians between baseline, end of RTX therapy, and 6 months after RTX therapy was observed in Dsg-3 titer (p < 0.001), in the CD8 (p = 0.009), and CD20 counts (p < 0.001). Multiple comparisons after Bonferroni adjustment confirmed such significant differences mainly between baseline and the end of RTX therapy and baseline and 6 months after RTX therapy. Only the anti-Dsg-3 titer at the end of RTX therapy demonstrated a slight positive correlation with the PDAI score at baseline (p = 0.046, r = 0.652). Conclusions: B-cell depletion adjuvant therapy in OPV patients demonstrated a significant impact on anti-Dsg-3 titer and B and T-cell lymphocyte subpopulations profile. Full article

(This article belongs to the Special Issue Biomolecules and Biomarkers in Head and Neck Medicine)

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Review

Jump to: Research, Other

15 pages, 299 KiB

Open AccessReview

Tears as a Source of Biomarkers in the Diagnosis of Graves’ Orbitopathy

by Diana Bajkowska, Małgorzata Szelachowska, Angelika Buczyńska, Adam Jacek Krętowski and Katarzyna Siewko

Biomolecules 2022, 12(11), 1620; https://doi.org/10.3390/biom12111620 - 02 Nov 2022

Cited by 4 | Viewed by 1875

Abstract

Thyroid eye disease (TED) is a poorly understood autoimmune manifestation of thyroid diseases most commonly associated with Graves’ disease. Due to a lack of specific biomarkers and uncertain signs and symptoms, Graves’ orbitopathy (GO) is challenging to diagnose early and treat effectively. Nowadays, [...] Read more.

Thyroid eye disease (TED) is a poorly understood autoimmune manifestation of thyroid diseases most commonly associated with Graves’ disease. Due to a lack of specific biomarkers and uncertain signs and symptoms, Graves’ orbitopathy (GO) is challenging to diagnose early and treat effectively. Nowadays, there is great interest in searching for precise molecular biomarkers for early detection, disease monitoring, and clinical management. Researchers are keen to identify novel methods to predict and diagnose diseases and to monitor patient therapeutic response. Tears, due to their direct contact with the eye and the fact that lacrimal glands can also be affected by the disease, could give new insights into the mechanisms taking place in thyroid-associated orbitopathy (TAO) and reveal potential promising biomarkers. Tear fluid offers the possibility of the non-invasive acquisition of a sample with a high protein content, thereby attracting continuously growing interest in the discovery of novel biomarkers. This article provides an up-to-date overview of the various putative tear-fluid biomarkers that have been identified. In this review, we present the potential use of tears as a diagnostic fluid and tool to investigate the mechanism of ocular diseases and discuss the future research directions in this area. Full article

(This article belongs to the Special Issue Biomolecules and Biomarkers in Head and Neck Medicine)

12 pages, 719 KiB

Open AccessReview

Are There Betel Quid Mixtures Less Harmful than Others? A Scoping Review of the Association between Different Betel Quid Ingredients and the Risk of Oral Submucous Fibrosis

by Nicola Cirillo, Peter Hung Duong, Wee Teng Er, Casey Thao Nhi Do, Manikkuwadura Eranda Harshan De Silva, Yining Dong, Sok Ching Cheong, Elizabeth Fitriana Sari, Michael J. McCullough, Pangzhen Zhang and Stephen S. Prime

Biomolecules 2022, 12(5), 664; https://doi.org/10.3390/biom12050664 - 02 May 2022

Cited by 11 | Viewed by 3406

Abstract

Oral submucous fibrosis (OSF) is a potentially malignant condition of the oral cavity characterized by progressive fibrosis of the submucosal tissues. OSF is typically associated with the use of betel quid (BQ), a chewing package made of natural products (e.g., areca nut, betel [...] Read more.

Oral submucous fibrosis (OSF) is a potentially malignant condition of the oral cavity characterized by progressive fibrosis of the submucosal tissues. OSF is typically associated with the use of betel quid (BQ), a chewing package made of natural products (e.g., areca nut, betel leaves), with or without smokeless tobacco. BQ ingredients contain pro-carcinogenic bioactive compounds, but also potentially protective biomolecules, and we have shown recently that the chemical properties of different BQ recipes vary, which may explain the unequal prevalence of OSF and oral cancer in BQ users in different geographical regions. Hence, this scoping review was aimed at evaluating the existing literature regarding different BQ compounds and their association with OSF. The repository of the National Library of Medicine (MEDLINE/PubMed), medRxiv databases, Google scholar, Baidu scholar, CNKI, and EBSCO were used to search for publications that investigated the association between BQ chewing and OSF up to November 2021. The search terminology was constructed using the keywords “betel quid” and “oral submucous fibrosis”, and their associated terms, with the use of Boolean operators. The search was conducted under Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines, together with clear inclusion and exclusion criteria. The review showed that the risk of developing OSF varied between different BQ recipes, and that chewing BQ mixtures containing betel inflorescence (BI) significantly increased the risk of OSF, as did the addition of tobacco. Conversely, the use of betel leaf in the mixture was likely to be protective, which may be due to the presence of polyphenols. Although further research is needed to determine the effect of individual BQ ingredients in the development of OSF, our pilot results provide the scope and rationale for informing future chemopreventive strategies for OSF and oral cancer in BQ chewers. Full article

(This article belongs to the Special Issue Biomolecules and Biomarkers in Head and Neck Medicine)

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16 pages, 1904 KiB

Open AccessReview

Identification of Metabolism-Associated Biomarkers for Early and Precise Diagnosis of Oral Squamous Cell Carcinoma

by Yuhan Wang, Xiaoxin Zhang, Shuai Wang, Zihui Li, Xinyang Hu, Xihu Yang, Yuxian Song, Yue Jing, Qingang Hu and Yanhong Ni

Biomolecules 2022, 12(3), 400; https://doi.org/10.3390/biom12030400 - 04 Mar 2022

Cited by 10 | Viewed by 3519

Abstract

The 5-year survival rate for oral squamous cell carcinoma (OSCC), one of the most common head and neck cancers, has not improved in the last 20 years. Poor prognosis of OSCC is the result of failure in early and precise diagnosis. Metabolic reprogramming, [...] Read more.

The 5-year survival rate for oral squamous cell carcinoma (OSCC), one of the most common head and neck cancers, has not improved in the last 20 years. Poor prognosis of OSCC is the result of failure in early and precise diagnosis. Metabolic reprogramming, including the alteration of the uptake and utilisation of glucose, amino acids and lipids, is an important feature of OSCC and can be used to identify its biomarkers for early and precise diagnosis. In this review, we summarise how recent findings of rewired metabolic networks in OSCC have facilitated early and precise diagnosis of OSCC. Full article

(This article belongs to the Special Issue Biomolecules and Biomarkers in Head and Neck Medicine)

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Other

Jump to: Research, Review

17 pages, 3346 KiB

Open AccessSystematic Review

Milk-Derived Proteins and Peptides in Head and Neck Carcinoma Treatment

by Theresa Wang, Xinyi Liu, Yah Ying Ng, Kiera Tarleton, Amy Tran, Thomas Tran, Wen Yue Xue, Paul Youssef, Peiyu Yuan, Daniel Zhang, Rita Paolini and Antonio Celentano

Biomolecules 2022, 12(2), 290; https://doi.org/10.3390/biom12020290 - 10 Feb 2022

Cited by 5 | Viewed by 2800

Abstract

Research investigating milk-derived proteins has brought to light the potential for their use as novel anticancer agents. This paper aims to systematically review studies examining the effectiveness of milk-derived proteins in the treatment of head and neck cancer. A systematic literature search of [...] Read more.

Research investigating milk-derived proteins has brought to light the potential for their use as novel anticancer agents. This paper aims to systematically review studies examining the effectiveness of milk-derived proteins in the treatment of head and neck cancer. A systematic literature search of Medline, Evidence-Based Medicine, and Web of Science databases including papers published from all dates was completed. Inter-rater reliability was high during the title, abstract, and full-text screening phases. Inclusion criteria, exclusion criteria, and data extraction were based on the PICOS tool and research questions. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-Analysis criteria. Eligible in vitro and in vivo studies (n = 8/658) evaluated lactoferrin, α-lactalbumin, and its complexes, such as HAMLET, BAMLET and lactalbumin-oleic acid complexes, as well as lactoperoxidase, whey, and casein. Their effectiveness in the treatment of head and neck cancer cells lines found that these compounds can inhibit tumour growth modulate cancer gene expression, and have cytotoxic effects on cancer cells. However, the exact mechanisms by which these effects are achieved are not well understood. Systematically designed, large, optimally controlled, collaborative studies, both in vitro and in vivo, will be required to gain a better understanding of their potential role in the treatment of head and neck cancer. Full article

(This article belongs to the Special Issue Biomolecules and Biomarkers in Head and Neck Medicine)

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19 pages, 289 KiB

Open AccessSystematic Review

A Systematic Review of MicroRNA Signatures Associated with the Progression of Leukoplakia with and without Epithelial Dysplasia

by Nadia Kaunein, Rishi Sanjay Ramani, Kendrick Koo, Caroline Moore, Antonio Celentano, Michael McCullough and Tami Yap

Biomolecules 2021, 11(12), 1879; https://doi.org/10.3390/biom11121879 - 14 Dec 2021

Cited by 4 | Viewed by 2568

Abstract

Oral cancer is a significant public health issue, being the eighth most common cancer worldwide with over 300,000 cases diagnosed annually. Early diagnosis and adequate management of oral potentially malignant disorders (OPMDs) before transformation into oral squamous cell carcinoma (OSCC) is critical to [...] Read more.

Oral cancer is a significant public health issue, being the eighth most common cancer worldwide with over 300,000 cases diagnosed annually. Early diagnosis and adequate management of oral potentially malignant disorders (OPMDs) before transformation into oral squamous cell carcinoma (OSCC) is critical to reduce deaths, morbidity, and to improve overall prognosis. MicroRNAs (miRNAs) are small noncoding RNAs involved in the post-transcriptional regulation of protein expression and implicated in the control of numerous cellular pathways and impacting physiological, developmental, and pathological processes. Dysregulation of miRNAs has been reported in many cancers and has been demonstrated to play a critical role in cancer initiation, progression, apoptosis, invasion and metastasis. This systematic review provides a comprehensive summary of the prevailing literature on miRNA signatures in OPMDs, specifically leukoplakia with or without oral epithelial dysplasia, and their utility in predicting malignant transformation into OSCC. Eighteen articles describing 73 unique and differentially expressed microRNAs met the criteria for inclusion in this review. We reviewed the characteristics and methodology for each of these studies and assessed the sensitivity and specificity of the studied miRNAs in predicting malignant transformation. This systematic review highlights the significant interest in miRNAs and their tremendous potential as prognostic markers for predicting the malignant transformation of OPMDs into OSCC. Full article

(This article belongs to the Special Issue Biomolecules and Biomarkers in Head and Neck Medicine)

16 pages, 1648 KiB

Open AccessSystematic Review

The Role of Glucose Transporters in Oral Squamous Cell Carcinoma

by Heinrich Botha, Camile S. Farah, Kendrick Koo, Nicola Cirillo, Michael McCullough, Rita Paolini and Antonio Celentano

Biomolecules 2021, 11(8), 1070; https://doi.org/10.3390/biom11081070 - 21 Jul 2021

Cited by 25 | Viewed by 3608

Abstract

Oral squamous cell carcinoma (OSCC) is a prevalent malignancy associated with a poor prognosis. The Warburg effect can be observed in OSCCs, with tumours requiring a robust glucose supply. Glucose transporters (GLUTs) and sodium-glucose co-transporters (SGLTs) are overexpressed in multiple malignancies, and are [...] Read more.

Oral squamous cell carcinoma (OSCC) is a prevalent malignancy associated with a poor prognosis. The Warburg effect can be observed in OSCCs, with tumours requiring a robust glucose supply. Glucose transporters (GLUTs) and sodium-glucose co-transporters (SGLTs) are overexpressed in multiple malignancies, and are correlated with treatment resistance, clinical factors, and poor overall survival (OS). We conducted a systematic review to evaluate the differences in GLUT/SGLT expression between OSCC and normal oral keratinocytes (NOK), as well as their role in the pathophysiology and prognosis of OSCC. A total of 85 studies were included after screening 781 papers. GLUT-1 is regularly expressed in OSCC and was found to be overexpressed in comparison to NOK, with high expression correlated to tumour stage, treatment resistance, and poor prognosis. No clear association was found between GLUT-1 and tumour grade, metastasis, and fluorodeoxyglucose (FDG) uptake. GLUT-3 was less thoroughly studied but could be detected in most samples and is generally overexpressed compared to NOK. GLUT-3 negatively correlated with overall survival (OS), but there was insufficient data for correlations with other clinical factors. Expression of GLUT-2/GLUT-4/GLUT-8/GLUT-13/SGLT-1/SGLT-2 was only evaluated in a small number of studies with no significant differences detected. GLUTs 7 and 14 have never been evaluated in OSCC. In conclusion, the data demonstrates that GLUT-1 and GLUT-3 have a role in the pathophysiology of OSCC and represent valuable biomarkers to aid OSCC diagnosis and prognostication. Other GLUTs are comparatively understudied and should be further analysed because they may hold promise to improve patient care. Full article

(This article belongs to the Special Issue Biomolecules and Biomarkers in Head and Neck Medicine)

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