Novel Promising Molecular Diagnostic and Prognostic Tools in Malignant Tumors

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 10687
In this Special Issue, we welcome research works regarding the implementation of molecular techniques in the risk assessment, early diagnosis, molecular typing, biological behavior prediction, prognosis evaluation and drug screening for malignant tumors.

Special Issue Editor

Special Issue Information

Dear Colleagues,

Recent research continues to shed light on the underlying molecular mechanisms contributing to cancer pathogenesis. Tumor molecular profiling paved the way for new, personalized, and effective therapies, greatly contributing to patients’ clinical outcomes.

The application of molecular techniques in the field of diagnosis has the potential to reshape the current approach to disease detection and management. Novel, sensitive molecular markers, often obtained through non-invasive procedures, offer the possibility of mass screening, leading to early disease diagnosis. Tumor molecular subtype identification aids in disease severity and progress determination, designating further diagnostic and treatment intervention needs and defining prognosis.

In this Special Issue, we welcome research works regarding the implementation of molecular techniques in the risk assessment, early diagnosis, molecular typing, biological behavior prediction, prognosis evaluation and drug screening for malignant tumors.

Prof. Stamatios E. Theocharis
Guest Editor

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Published Papers (5 papers)

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Research

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15 pages, 885 KiB  
Article
HLA-G 14bp Ins/Del Polymorphism, Plasma Level of Soluble HLA-G, and Association with IL-6/IL-10 Ratio and Survival of Glioma Patients
by Maria Bucova, Kristina Kluckova, Jan Kozak, Boris Rychly, Magda Suchankova, Marian Svajdler, Viktor Matejcik, Juraj Steno, Eszter Zsemlye and Vladimira Durmanova
Diagnostics 2022, 12(5), 1099; https://doi.org/10.3390/diagnostics12051099 - 27 Apr 2022
Cited by 4 | Viewed by 1402
Abstract
HLA-G is an immune checkpoint molecule with immunosuppressive and anti-inflammatory activities, and its expression and level of its soluble form (sHLA-G) may play an important role in tumor prognosis. The HLA-G 14bp ins/del polymorphism and the plasma level of soluble HLA-G (sHLA-G) were [...] Read more.
HLA-G is an immune checkpoint molecule with immunosuppressive and anti-inflammatory activities, and its expression and level of its soluble form (sHLA-G) may play an important role in tumor prognosis. The HLA-G 14bp ins/del polymorphism and the plasma level of soluble HLA-G (sHLA-G) were investigated by a polymerase chain reaction and ELISA, respectively, in 59 glioma patients. A significantly higher proportion of glioma patients had the 14 nt insert in both homozygous and heterozygous states compared to the control group. Glioma patients also had higher plasma levels of sHLA-G. Patients with methylated MGMT promoters had lower levels of sHLA-G than those with unmethylated MGMT promoters. The level of sHLA-G negatively correlated with the overall survival of patients. Glioblastoma patients who survived more than one year after diagnosis had lower levels of sHLA-G than those surviving less than one year. Patients with sHLA-G levels below the cut-off value of 40 U/mL survived significantly longer than patients with sHLA-G levels above 40 U/mL. The levels of sHLA-G were also negatively correlated with the level of IL-6 (p = 0.0004) and positively with IL-10/IL-6 (p = 0.046). Conclusion: The presence of the 14 nt insert in both homozygous and heterozygous states of the HLA-G 14bp ins/del polymorphism is more frequent in glioma patients and the elevated plasma levels of sHLA-G are negatively associated with their survival. Full article
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16 pages, 3994 KiB  
Article
Alpha-Enolase (ENO1) Correlates with Invasiveness of Cutaneous Melanoma—An In Vitro and a Clinical Study
by Miriam Hippner, Michal Majkowski, Przemyslaw Biecek, Teresa Szkudlarek, Aleksandra Simiczyjew, Malgorzata Pieniazek, Dorota Nowak, Arkadiusz Miazek and Piotr Donizy
Diagnostics 2022, 12(2), 254; https://doi.org/10.3390/diagnostics12020254 - 20 Jan 2022
Cited by 4 | Viewed by 2197
Abstract
Alpha-enolase (ENO1) is a glycolytic metalloenzyme, and its overexpression occurs in numerous cancers, contributing to cancer cell survival, proliferation, and maintenance of the Warburg effect. Patients with an overexpression of ENO1 have a poor prognosis. The aim of the present study was to [...] Read more.
Alpha-enolase (ENO1) is a glycolytic metalloenzyme, and its overexpression occurs in numerous cancers, contributing to cancer cell survival, proliferation, and maintenance of the Warburg effect. Patients with an overexpression of ENO1 have a poor prognosis. The aim of the present study was to investigate the prognostic significance of ENO1 in surgical resections from 112 melanoma patients and to assess its expression and enzymatic activity in normoxia and hypoxia in several melanoma cell lines. Overexpression of ENO1 in tumor cells from patients was correlated with unfavorable prognosticators such as Breslow thickness, Clark level, mitotic activity, and the presence of ulceration. The expression of ENO1 also positively correlated with a greater thickness of the neoplastic infiltrate and a worse long-term prognosis for patients with cutaneous melanoma. We report significantly higher expression of ENO1 in melanoma cell lines in comparison to normal melanocytes. To conclude, our in vitro and clinical models showed that overexpression of ENO1 promotes invasiveness of melanoma cells and correlates with aggressive clinical behavior. These observations open the way to further search of a potential prognostic and therapeutic target in cutaneous melanoma. Full article
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25 pages, 3094 KiB  
Article
Recurrence in Oral Premalignancy: Clinicopathologic and Immunohistochemical Analysis
by Maria Georgaki, Dimitris Avgoustidis, Vasileios Ionas Theofilou, Evangelia Piperi, Efstathios Pettas, Demos G. Kalyvas, Dimitrios Vlachodimitropoulos, Christos Perisanidis, Andreas C. Lazaris and Nikolaos G. Nikitakis
Diagnostics 2021, 11(5), 872; https://doi.org/10.3390/diagnostics11050872 - 12 May 2021
Cited by 5 | Viewed by 2055
Abstract
Oral leukoplakia (OL) has a propensity for recurrence and malignant transformation (MT). Herein, we evaluate sociodemographic, clinical, microscopic and immunohistochemical parameters as predictive factors for OL recurrence, also comparing primary lesions (PLs) with recurrences. Thirty-three patients with OL, completely removed either by excisional [...] Read more.
Oral leukoplakia (OL) has a propensity for recurrence and malignant transformation (MT). Herein, we evaluate sociodemographic, clinical, microscopic and immunohistochemical parameters as predictive factors for OL recurrence, also comparing primary lesions (PLs) with recurrences. Thirty-three patients with OL, completely removed either by excisional biopsy or by laser ablation following incisional biopsy, were studied. Selected molecules associated with the STAT3 oncogenic pathway, including pSTAT3, Bcl-xL, survivin, cyclin D1 and Ki-67, were further analyzed. A total of 135 OL lesions, including 97 PLs and 38 recurrences, were included. Out of 97 PLs, 31 recurred at least once and none of them underwent MT, during a mean follow-up time of 48.3 months. There was no statistically significant difference among the various parameters in recurrent vs. non-recurrent PLs, although recurrence was most frequent in non-homogeneous lesions (p = 0.087) and dysplastic lesions recurred at a higher percentage compared to hyperplastic lesions (34.5% vs. 15.4%). Lower levels of Bcl-xL and survivin were identified as significant risk factors for OL recurrence. Recurrences, although smaller and more frequently homogeneous and non-dysplastic compared to their corresponding PLs, exhibited increased immunohistochemical expression of oncogenic molecules, especially pSTAT3 and Bcl-xL. Our results suggest that parameters associated with recurrence may differ from those that affect the risk of progression to malignancy and support OL management protocols favoring excision and close monitoring of all lesions. Full article
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Review

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17 pages, 763 KiB  
Review
Unraveling the Epigenetic Role and Clinical Impact of Histone Deacetylases in Neoplasia
by Dimitrios Goutas, Stamatios Theocharis and Gerasimos Tsourouflis
Diagnostics 2021, 11(8), 1346; https://doi.org/10.3390/diagnostics11081346 - 26 Jul 2021
Cited by 15 | Viewed by 1882
Abstract
Histone deacetylases (HDACs) have long been implicated in tumorigenesis and tumor progression demonstrating their important participation in neoplasia. Therefore, numerous studies have been performed, highlighting the mechanism of HDACs action in tumor cells and demonstrating the potential role of HDAC inhibitors in the [...] Read more.
Histone deacetylases (HDACs) have long been implicated in tumorigenesis and tumor progression demonstrating their important participation in neoplasia. Therefore, numerous studies have been performed, highlighting the mechanism of HDACs action in tumor cells and demonstrating the potential role of HDAC inhibitors in the treatment of different cancer types. The outcome of these studies further delineated and strengthened the solid role that HDACs and epigenetic modifications exert in neoplasia. These results have spread promise regarding the potential use of HDACs as prospective therapeutic targets. Nevertheless, the clinical significance of HDAC expression and their use as biomarkers in cancer has not been extensively elucidated. The aim of our study is to emphasize the clinical significance of HDAC isoforms expression in different tumor types and the correlations noted between the clinicopathological parameters of tumors and patient outcomes. We further discuss the obstacles that the next generation HDAC inhibitors need to overcome, for them to become more potent. Full article
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Other

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10 pages, 1944 KiB  
Case Report
Undifferentiated Carcinoma with Osteoclast-Like Giant Cells of the Common Bile Duct: A Case Report of a Rare Entity at an Unusual Location
by Chuan-Han Chen and Hsin-Ni Li
Diagnostics 2022, 12(7), 1517; https://doi.org/10.3390/diagnostics12071517 - 21 Jun 2022
Viewed by 1554
Abstract
Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) is a rare variant of carcinoma with unique radiological and pathological features. This unusual carcinoma has been reported in a variety of organs and pancreas is the most frequently involved anatomical site. UCOGC of pancreas attains [...] Read more.
Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) is a rare variant of carcinoma with unique radiological and pathological features. This unusual carcinoma has been reported in a variety of organs and pancreas is the most frequently involved anatomical site. UCOGC of pancreas attains a relatively indolent clinical behavior and should be distinguished from ordinary pancreatobiliary adenocarcinoma. This paper presents the first case of UCOGC involving the entire segment of common bile duct (CBD) and common hepatic duct (CHD) without extending to the pancreatic tissue. Getting familiar with its clinical, radiological and pathological characters can help establish accurate diagnosis despite the occurrence of an unusual location. Full article
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