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      ZNF-281 as the Potential Diagnostic Marker of Oral Squamous Cell Carcinoma

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          Abstract

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          Zinc-finger-281’s (ZNF-281’s) influence on carcinogenesis, progression and metastasis (through epithelial–mesenchymal transition induction) and its association with poor prognosis have been reported in many cancers. However, while reviewing the literature, there has been no mention of ZNF-281’s activity in oral squamous cell carcinoma (OSCC). In this pilot study, we analyzed ZNF-281′s expression and the impact of various clinical factors on its levels in OSCC patients. We aimed to verify whether ZNF-281 could potentially become a marker that will enable early OSCC diagnosis and help in assessing its prognostic value, specifically in terms of overall survival. Our findings show that the ZNF-281 H-score and mRNA expression were significantly decreased in OSCC when compared to healthy tissue, proving that ZNF-281 could become an OSCC-specific marker. ZNF-281’s role in OSCC should be further investigated as it is a promising candidate for an OSCC marker.

          Abstract

          ZNF-281 is a zinc finger factor which can lead to cancer progression and metastasis. Its up-regulation reported in many cancers was correlated with metastasis and worsened patients’ prognosis. This is the first study describing ZNF-281 in the context of OSCC. Oral tissue samples drawn from 66 OSCC patients and 36 control patients were collected to determine protein (using immunochemistry and the semi-quantitative H-score method) and mRNA expression levels (using the RT-qPCR reaction). Our aim was to assess the ZNF-281 expression level in OSCC and the control group. Moreover, we determined the impact of ZNF-281 on survival parameters and the association of diversified clinical parameters with ZNF-281 expression. Clinical factors such as grade, AJCC stage and radiotherapy have an impact on the ZNF-281 H-score level, whereas AJCC stage and grade have an influence on ZNF-281 mRNA expression. Our survival analysis indicated that the impact on overall survival is not statistically significant, and the prognostic potential of ZNF-281 is rather limited. Our findings show that both levels of the ZNF-281 H-score and mRNA are decreased in OSCC in comparison to normal tissue. Moreover, we estimated that the H-score can differentiate normal tissue from OSCC with a sensitivity of 97% and specificity of 93.7%.

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          Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK): Explanation and Elaboration

          The REMARK “elaboration and explanation” guideline, by Doug Altman and colleagues, provides a detailed reference for authors on important issues to consider when designing, conducting, and analyzing tumor marker prognostic studies.
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            Zinc finger proteins in cancer progression

            Zinc finger proteins are the largest transcription factor family in human genome. The diverse combinations and functions of zinc finger motifs make zinc finger proteins versatile in biological processes, including development, differentiation, metabolism and autophagy. Over the last few decades, increasing evidence reveals the potential roles of zinc finger proteins in cancer progression. However, the underlying mechanisms of zinc finger proteins in cancer progression vary in different cancer types and even in the same cancer type under different types of stress. Here, we discuss general mechanisms of zinc finger proteins in transcription regulation and summarize recent studies on zinc finger proteins in cancer progression. In this review, we also emphasize the importance of further investigations in elucidating the underlying mechanisms of zinc finger proteins in cancer progression.
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              Functional Roles of E6 and E7 Oncoproteins in HPV-Induced Malignancies at Diverse Anatomical Sites

              Approximately 200 human papillomaviruses (HPVs) infect human epithelial cells, of which the alpha and beta types have been the most extensively studied. Alpha HPV types mainly infect mucosal epithelia and a small group of these causes over 600,000 cancers per year worldwide at various anatomical sites, especially anogenital and head-and-neck cancers. Of these the most important is cervical cancer, which is the leading cause of cancer-related death in women in many parts of the world. Beta HPV types infect cutaneous epithelia and may contribute towards the initiation of non-melanoma skin cancers. HPVs encode two oncoproteins, E6 and E7, which are directly responsible for the development of HPV-induced carcinogenesis. They do this cooperatively by targeting diverse cellular pathways involved in the regulation of cell cycle control, of apoptosis and of cell polarity control networks. In this review, the biological consequences of papillomavirus targeting of various cellular substrates at diverse anatomical sites in the development of HPV-induced malignancies are highlighted.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                28 May 2021
                June 2021
                : 13
                : 11
                : 2661
                Affiliations
                [1 ]Department of Oral Surgery, Medical University of Gdańsk, 7 Dębinki Street, 80-211 Gdańsk, Poland; olga.szot@ 123456gumed.edu.pl
                [2 ]International Research Agenda 3P—Medicine Laboratory, Medical University of Gdańsk, 3A Sklodowskiej-Curie Street, 80-210 Gdansk, Poland
                [3 ]Department of Pathomorphology, University of Warmia and Mazury, 18 Żołnierska Street, 10-561 Olsztyn, Poland; aleksandra.sejda@ 123456uwm.edu.pl
                [4 ]Department of Molecular Medicine, Medical University of Gdańsk, 7 Dębinki Street, 80-211 Gdańsk, Poland; ssak@ 123456gumed.edu.pl
                [5 ]Division of Radiotherapy, IEO European Institute of Oncology, IRCCS, 435 Ripamonti Street, 20-141 Milan, Italy; barbara.jereczek@ 123456ieo.it
                [6 ]Department of Oncology and Hemato-Oncology, University of Milan, 7 Festa del Perdono Street, 20-112 Milan, Italy
                Author notes
                [* ]Correspondence: anna.starzynska@ 123456gumed.edu.pl (A.S.); b.sobocki@ 123456gumed.edu.pl (B.K.S.); Tel.: +48-58-349-15-71 (A.S.)
                [†]

                These authors contributed equally to this paper as co-first authors.

                Author information
                https://orcid.org/0000-0001-6900-0429
                https://orcid.org/0000-0002-8110-7402
                Article
                cancers-13-02661
                10.3390/cancers13112661
                8197962
                34071380
                7f38035a-e860-42d3-a84c-22349864a548
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 26 April 2021
                : 25 May 2021
                Categories
                Article

                oral squamous cell carcinoma,znf-281,diagnosis
                oral squamous cell carcinoma, znf-281, diagnosis

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