Editorial

2 pages, 160 KiB

Open AccessEditorial

Genetics and Molecular Biology of Head and Neck Cancer

by Krzysztof Szyfter

Biomolecules 2021, 11(9), 1293; https://doi.org/10.3390/biom11091293 - 31 Aug 2021

Cited by 4 | Viewed by 1970

Head and neck cancer (HNC) is a multistep process proceeding from single gene mutations generated by carcinogens to the substantial dysregulation of metabolic processes [...] Full article

(This article belongs to the Special Issue Genetics and Molecular Biology of Head and Neck Cancer)

Research

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14 pages, 3415 KiB

Open AccessArticle

Loss of the MAF Transcription Factor in Laryngeal Squamous Cell Carcinoma

by Joanna Janiszewska, Magdalena Bodnar, Julia Paczkowska, Adam Ustaszewski, Maciej J. Smialek, Lukasz Szylberg, Andrzej Marszalek, Katarzyna Kiwerska, Reidar Grenman, Krzysztof Szyfter, Malgorzata Wierzbicka, Maciej Giefing and Malgorzata Jarmuz-Szymczak

Biomolecules 2021, 11(7), 1035; https://doi.org/10.3390/biom11071035 - 15 Jul 2021

Cited by 4 | Viewed by 2784

Abstract

MAF is a transcription factor that may act either as a tumor suppressor or as an oncogene, depending on cell type. We have shown previously that the overexpressed miR-1290 influences MAF protein levels in LSCC (laryngeal squamous cell carcinoma) cell lines. In this [...] Read more.

MAF is a transcription factor that may act either as a tumor suppressor or as an oncogene, depending on cell type. We have shown previously that the overexpressed miR-1290 influences MAF protein levels in LSCC (laryngeal squamous cell carcinoma) cell lines. In this study, we shed further light on the interaction between miR-1290 and MAF, as well as on cellular MAF protein localization in LSCC. We confirmed the direct interaction between miR-1290 and MAF 3′UTR by a dual-luciferase reporter assay. In addition, we used immunohistochemistry staining to analyze MAF protein distribution and observed loss of MAF nuclear expression in 58% LSCC samples, of which 10% showed complete absence of MAF, compared to nuclear and cytoplasmatic expression in 100% normal mucosa. Using TCGA data, bisulfite pyrosequencing and CNV analysis, we excluded the possibility that loss-of-function mutations, promoter region DNA methylation or CNV are responsible for MAF loss in LSCC. Finally, we identified genes involved in the regulation of apoptosis harboring the MAF binding motif in their promoter region by applied FIMO and DAVID GO analysis. Our results highlight the role of miR-1290 in suppressing MAF expression in LSCC. Furthermore, MAF loss or mislocalization in FFPE LSCC tumor samples might suggest that MAF acts as a LSCC tumor suppressor by regulating apoptosis. Full article

(This article belongs to the Special Issue Genetics and Molecular Biology of Head and Neck Cancer)

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9 pages, 909 KiB

Open AccessArticle

Expression of Programmed Death Receptor 1 (PD-1) Gene and Its Ligand (PD-L1) in Patients with Laryngeal Cancer

by Andrzej Kowalski, Katarzyna Malinowska, Jurek Olszewski and Hanna Zielińska-Bliźniewska

Biomolecules 2021, 11(7), 970; https://doi.org/10.3390/biom11070970 - 01 Jul 2021

Cited by 5 | Viewed by 2391

Abstract

(1) Background: The interaction of the programmed death receptor (PD-1) with its ligand 1 (PD-L1) allows cancer cells to escape from the control of the immune system. Research evaluating the expression of immune checkpoint genes in the tissues of laryngeal tumors may contribute [...] Read more.

(1) Background: The interaction of the programmed death receptor (PD-1) with its ligand 1 (PD-L1) allows cancer cells to escape from the control of the immune system. Research evaluating the expression of immune checkpoint genes in the tissues of laryngeal tumors may contribute to the introduction of new effective immunotherapeutic methods in this group of neoplasms. The aim of this study was to evaluate the expression of the gene for the programmed death receptor (PD-1) and its ligand (PD-L1) in laryngeal tumors (T1, T2, T3) in patients without lymph node involvement and distant metastases. (2) Methods: The study included 73 patients: 39 of them were diagnosed with carcinoma planoepiteliale keratodes (study group) and 34 with nasal septal deviation undergoing septoplasty (control group). Biological material for molecular tests (Real time PCR) was collected during surgical procedures. Furthermore, all study participants completed a questionnaire regarding, among others, smoking and body weight. (3) Results: Gene expression for programmed death receptor 1 (PD-1) and its ligand 1 (PD-L1) was, statistically, significantly higher (p < 0.0001) in tumor tissue than in unchanged mucosa. Moreover, it was found that the greater the tumor size, the higher the expression level of the tested molecules. (4) Conclusions: Although further research on the role of the PD-1/PD-L1 pathway in laryngeal tumors is necessary, the presented reports are promising and may constitute a contribution to considerations on the introduction of targeted immunotherapy with anti-PD1 and anti-PD-L1 monoclonal antibodies in the treatment of these tumors. Full article

(This article belongs to the Special Issue Genetics and Molecular Biology of Head and Neck Cancer)

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13 pages, 1794 KiB

Open AccessEditor’s ChoiceArticle

The m⁶A RNA Modification Quantity and mRNA Expression Level of RNA Methylation-Related Genes in Head and Neck Squamous Cell Carcinoma Cell Lines and Patients

by Kamila Romanowska, Agnieszka A. Rawłuszko-Wieczorek, Łukasz Marczak, Agnieszka Kosińska, Wiktoria M. Suchorska and Wojciech Golusiński

Biomolecules 2021, 11(6), 908; https://doi.org/10.3390/biom11060908 - 18 Jun 2021

Cited by 5 | Viewed by 2667

Abstract

RNA methylation at the nitrogen sixth of adenosine (m⁶A, N⁶-methyladenosine) is the most abundant RNA modification which plays a crucial role in all RNA metabolic aspects. Recently, m⁶A modification has been assigned to mediate the biological processes [...] Read more.

RNA methylation at the nitrogen sixth of adenosine (m⁶A, N⁶-methyladenosine) is the most abundant RNA modification which plays a crucial role in all RNA metabolic aspects. Recently, m⁶A modification has been assigned to mediate the biological processes of cancer cells, but their significance in HNSCC development is still poorly described. Thus, the main aim of this study was to globally quantify m⁶A modification by the mass spectrometry approach and determine the mRNA expression level of selected m⁶A RNA methyltransferase (METTL3), demethylase (FTO), and m⁶A readers (YTHDF2, YTHDC2) in 45 HNSCC patients and 4 cell lines (FaDu, Detroit 562, A-253 and SCC-15) using qPCR. In the results, we have not observed differences in the global amount of m⁶A modification and the mRNA level of the selected genes between the cancerous and paired-matched histopathologically unchanged tissues from 45 HNSCC patients. However, we have found a positive correlation between selected RNA methylation machinery genes expression and m⁶A abundance on total RNA and characterized the transcript level of those genes in the HNSCC cell lines. Moreover, the lack of global m⁶A differences between cancerous and histopathologically unchanged tissues suggests that m⁶A alterations in specific RNA sites may specifically influence HNSCC tumorigenesis. Full article

(This article belongs to the Special Issue Genetics and Molecular Biology of Head and Neck Cancer)

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10 pages, 2686 KiB

Open AccessArticle

Assessment of MicroRNA (miR)-365 Effects on Oral Squamous Carcinoma Cell Line Phenotypes

by Jeffrey Coon and Karl Kingsley

Biomolecules 2021, 11(6), 874; https://doi.org/10.3390/biom11060874 - 12 Jun 2021

Cited by 6 | Viewed by 2950

Abstract

miR-365 is a microRNA that regulates transcription and has been demonstrated to promote oncogenesis and metastasis in some cancers while suppressing these effects in others. Virtually no information is known about the presence or function of miR-365 in oral cancers. Based upon this [...] Read more.

miR-365 is a microRNA that regulates transcription and has been demonstrated to promote oncogenesis and metastasis in some cancers while suppressing these effects in others. Virtually no information is known about the presence or function of miR-365 in oral cancers. Based upon this information, the primary goal of this project was to evaluate the expression of miR-365 in existing oral cancer cell lines. Five commercially available oral cancer cell lines (SCC4, SCC9, SCC15, SCC25, and CAL27) were obtained and cultured. RNA was then screened by PCR using primers specific for miR-365, as well as matrix metalloproteinase (MMP-2) and a downstream cancer stem cell regulator (NKX2.1), and structural and metabolic standards (beta actin, GAPDH). miR-365 was detected among these oral cancers, and some cells also expressed NKX2.1 and MMP-2, which correlated with miR-365 levels. The relative expression of miR-365, NKX2.1, and MMP-2 RNA was higher than expected. Transfection of miR-365 resulted in a significant increase in proliferation, which was not observed in the negative controls. These data appear to confirm miR-365 expression in oral cancers, which may also be correlated with MMP-2 and NKX2.1 expression. Moreover, the fastest growing oral cancers with the highest viability produced the most miR-365. In addition, miR-365 transfected into cells significantly increased growth, even in normal cells. More research is needed to elucidate the pathways responsible for these observations. Full article

(This article belongs to the Special Issue Genetics and Molecular Biology of Head and Neck Cancer)

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16 pages, 338 KiB

Open AccessArticle

Survival of Laryngeal Cancer Patients Depending on Zinc Serum Level and Oxidative Stress Genotypes

by Jakub Lubiński, Ewa Jaworowska, Róża Derkacz, Wojciech Marciniak, Katarzyna Białkowska, Piotr Baszuk, Rodney J. Scott and Jan A. Lubiński

Biomolecules 2021, 11(6), 865; https://doi.org/10.3390/biom11060865 - 10 Jun 2021

Cited by 18 | Viewed by 3288

Abstract

Stress contributes to various aspects of malignancy and could influence survival in laryngeal cancer patients. Among antioxidant mechanisms, zinc and the antioxidant enzymes superoxide dismutase 2, catalase and glutathione peroxidase 1 play a major role. The aim of this study was a prospective [...] Read more.

Stress contributes to various aspects of malignancy and could influence survival in laryngeal cancer patients. Among antioxidant mechanisms, zinc and the antioxidant enzymes superoxide dismutase 2, catalase and glutathione peroxidase 1 play a major role. The aim of this study was a prospective evaluation of the survival of patients with laryngeal cancer in relation to serum levels of zinc in combination with functional genotype differences of three key antioxidant enzymes. The study group consisted of 300 patients treated surgically for laryngeal cancer. Serum zinc levels and common polymorphisms in SOD2, CAT and GPX1 were analyzed. The risk of death in patients with the lowest zinc levels was increased in comparison with patients with the highest levels. Polymorphisms of antioxidant genes by themselves were not correlated with survival, however, serum zinc level impact on survival was stronger for SOD2 TC/TT and CAT CC variants. GPX1 polymorphisms did not correlate with zinc levels regarding survival. In conclusion, serum zinc concentration appears to be an important prognostic factor for survival of patients diagnosed with laryngeal cancer. When higher zinc levels were correlated with polymorphisms in SOD2 and CAT a further increase in survival was observed. Full article

(This article belongs to the Special Issue Genetics and Molecular Biology of Head and Neck Cancer)

14 pages, 747 KiB

Open AccessArticle

Detection of PIK3CA Gene Mutation in Head and Neck Squamous Cell Carcinoma Using Droplet Digital PCR and RT-qPCR

by Edyta M. Borkowska, Magda Barańska, Magdalena Kowalczyk and Wioletta Pietruszewska

Biomolecules 2021, 11(6), 818; https://doi.org/10.3390/biom11060818 - 31 May 2021

Cited by 6 | Viewed by 3841

Abstract

Head and neck squamous cell carcinomas (HNSCC) are the seventh cause of human malignancy with low survival rate due to late diagnosis and treatment. Its etiology is diverse; however genetic factors are significant. The most common mutations in HNSCC were found in the [...] Read more.

Head and neck squamous cell carcinomas (HNSCC) are the seventh cause of human malignancy with low survival rate due to late diagnosis and treatment. Its etiology is diverse; however genetic factors are significant. The most common mutations in HNSCC were found in the genes: PIK3CA (10–12%), BRCA1 (6%), and BRCA2 (7–9%). In some cases, these biomarkers correlate with recurrences or survival showing a potential of prognostic and predictive value. A total of 113 formalin-fixed paraffin embedded (FFPE) tumor samples were collected from patients with HNSCC (oral cavity: 35 (31.0%); oropharynx: 30 (26.0%); larynx: 48 (43.0%)). We examined PIK3CA H1047R mutation by Real Time PCR (RT-qPCR) and droplet digital PCR (ddPCR). BRCA1 and BRCA2 mutations were analyzed by RT-qPCR while p16 protein expression was assessed by immunohistochemistry. Finally, we identified HPV infection by RT-qPCR. The relationships between genomic alterations and clinical parameters were assessed using the Yates’ corrected Chi-squared test or Fisher’s exact test for nominal variables. Kaplan Meier plots were applied for survival analysis. Our results revealed 9 PIK3CA H1047R mutations detected by ddPCR: 8 of them were negative in RT-qPCR. Due to the use of different methods to test the presence of the PIK3CA gene mutation, different treatment decisions might be made. That is why it is so important to use the most sensitive methods available. We confirmed the usefulness of ddPCR in the PIK3CA mutation assessment in FFPE samples. Full article

(This article belongs to the Special Issue Genetics and Molecular Biology of Head and Neck Cancer)

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8 pages, 1471 KiB

Open AccessCommunication

Assessing Various Control Samples for Microarray Gene Expression Profiling of Laryngeal Squamous Cell Carcinoma

by Adam Ustaszewski, Magdalena Kostrzewska-Poczekaj, Joanna Janiszewska, Malgorzata Jarmuz-Szymczak, Malgorzata Wierzbicka, Joanna Marszal, Reidar Grénman and Maciej Giefing

Biomolecules 2021, 11(4), 588; https://doi.org/10.3390/biom11040588 - 16 Apr 2021

Cited by 2 | Viewed by 2126

Abstract

Selection of optimal control samples is crucial in expression profiling tumor samples. To address this issue, we performed microarray expression profiling of control samples routinely used in head and neck squamous cell carcinoma studies: human bronchial and tracheal epithelial cells, squamous cells obtained [...] Read more.

Selection of optimal control samples is crucial in expression profiling tumor samples. To address this issue, we performed microarray expression profiling of control samples routinely used in head and neck squamous cell carcinoma studies: human bronchial and tracheal epithelial cells, squamous cells obtained by laser uvulopalatoplasty and tumor surgical margins. We compared the results using multidimensional scaling and hierarchical clustering versus tumor samples and laryngeal squamous cell carcinoma cell lines. A general observation from our study is that the analyzed cohorts separated according to two dominant factors: “malignancy”, which separated controls from malignant samples and “cell culture-microenvironment” which reflected the differences between cultured and non-cultured samples. In conclusion, we advocate the use of cultured epithelial cells as controls for gene expression profiling of cancer cell lines. In contrast, comparisons of gene expression profiles of cancer cell lines versus surgical margin controls should be treated with caution, whereas fresh frozen surgical margins seem to be appropriate for gene expression profiling of tumor samples. Full article

(This article belongs to the Special Issue Genetics and Molecular Biology of Head and Neck Cancer)

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Review

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22 pages, 1458 KiB

Open AccessReview

Paradoxical Roles of Desmosomal Components in Head and Neck Cancer

by Yin-Qiao Liu, Hai-Ying Zou, Jian-Jun Xie and Wang-Kai Fang

Biomolecules 2021, 11(6), 914; https://doi.org/10.3390/biom11060914 - 20 Jun 2021

Cited by 14 | Viewed by 4390

Abstract

Desmosomes are intercellular adhesion complexes involved in various aspects of epithelial pathophysiology, including tissue homeostasis, morphogenesis, and disease development. Recent studies have reported that the abnormal expression of various desmosomal components correlates with tumor progression and poor survival. In addition, desmosomes have been [...] Read more.

Desmosomes are intercellular adhesion complexes involved in various aspects of epithelial pathophysiology, including tissue homeostasis, morphogenesis, and disease development. Recent studies have reported that the abnormal expression of various desmosomal components correlates with tumor progression and poor survival. In addition, desmosomes have been shown to act as a signaling platform to regulate the proliferation, invasion, migration, morphogenesis, and apoptosis of cancer cells. The occurrence and progression of head and neck cancer (HNC) is accompanied by abnormal expression of desmosomal components and loss of desmosome structure. However, the role of desmosomal components in the progression of HNC remains controversial. This review aims to provide an overview of recent developments showing the paradoxical roles of desmosomal components in tumor suppression and promotion. It offers valuable insights for HNC diagnosis and therapeutics development. Full article

(This article belongs to the Special Issue Genetics and Molecular Biology of Head and Neck Cancer)

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17 pages, 360 KiB

Open AccessEditor’s ChoiceReview

MicroRNA as a Novel Biomarker in the Diagnosis of Head and Neck Cancer

by Jacek Kabzinski, Monika Maczynska and Ireneusz Majsterek

Biomolecules 2021, 11(6), 844; https://doi.org/10.3390/biom11060844 - 05 Jun 2021

Cited by 25 | Viewed by 4372

Abstract

Head and neck squamous cell carcinoma is the sixth most common cancer worldwide, with 890,000 new cases and 450,000 deaths in 2018, and although the survival statistics for some patient groups are improving, there is still an urgent need to find a fast [...] Read more.

Head and neck squamous cell carcinoma is the sixth most common cancer worldwide, with 890,000 new cases and 450,000 deaths in 2018, and although the survival statistics for some patient groups are improving, there is still an urgent need to find a fast and reliable biomarker that allows early diagnosis. This niche can be filled by microRNA, small single-stranded non-coding RNA molecules, which are expressed in response to specific events in the body. This article presents the potential use of microRNAs in the diagnosis of HNSCC, compares the advances in this field to other diseases, especially other cancers, and discusses the detailed use of miRNA as a biomarker in profiling and predicting the treatment outcome with radiotherapy and immunotherapy. Potential problems and difficulties related to the development of this promising technology, and areas on which future research should be focused in order to overcome these difficulties, were also indicated. Full article

(This article belongs to the Special Issue Genetics and Molecular Biology of Head and Neck Cancer)

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