SRY-Related Transcription Factors in Head and Neck Squamous Cell Carcinomas: In Silico Based Analysis

Tomasz Kolenda; Zuzanna Graczyk; Barbara Żarska; Wojciech Łosiewski; Mikołaj Smolibowski; Adrian Wartecki; Joanna Kozłowska-Masłoń; Kacper Guglas; Anna Florczak; Urszula Kazimierczak; Anna Teresiak; Katarzyna Lamperska

doi:10.3390/cimb45120592

SRY-Related Transcription Factors in Head and Neck Squamous Cell Carcinomas: In Silico Based Analysis

Curr Issues Mol Biol. 2023 Nov 24;45(12):9431-9449. doi: 10.3390/cimb45120592.

Authors

Tomasz Kolenda^{1

2}, Zuzanna Graczyk^{3

4}, Barbara Żarska³, Wojciech Łosiewski³, Mikołaj Smolibowski³, Adrian Wartecki³, Joanna Kozłowska-Masłoń^{1

2

5}, Kacper Guglas^{1

2

6}, Anna Florczak^{3

7}, Urszula Kazimierczak^{3

7}, Anna Teresiak^{1

2}, Katarzyna Lamperska^{1

2}

Affiliations

¹ Laboratory of Cancer Genetics, Greater Poland Cancer Centre, Garbary 15, 61-866 Poznan, Poland.
² Research and Implementation Unit, Greater Poland Cancer Centre, Garbary 15, 61-866 Poznan, Poland.
³ Department of Cancer Immunology, Poznan University of Medical Sciences, 8 Rokietnicka Street, 60-806 Poznan, Poland.
⁴ Institute of Human Genetics, Polish Academy of Sciences, Strzeszynska 32, 60-479 Poznan, Poland.
⁵ Institute of Human Biology and Evolution, Faculty of Biology, Adam Mickiewicz University, Uniwersytetu Poznańskiego 6, 61-614 Poznan, Poland.
⁶ Postgraduate School of Molecular Medicine, Medical University of Warsaw, Żwirki i Wigury 61, 02-091 Warsaw, Poland.
⁷ Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, Garbary 15, 61-688 Poznan, Poland.

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cancer and the fifth cause of cancer-related deaths worldwide with a poor 5-year survival. SOX family genes play a role in the processes involved in cancer development such as epithelial-mesenchymal transition (EMT), the maintenance of cancer stem cells (CSCs) and the regulation of drug resistance. We analyzed the expression of SOX2-OT, SOX6, SOX8, SOX21, SOX30 and SRY genes in HNSCC patients using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, to assess their biological role and their potential utility as biomarkers. We demonstrated statistically significant differences in expression between normal and primary tumor tissues for SOX6, SOX8, SOX21 and SOX30 genes and pointed to SOX6 as the one that met the independent diagnostic markers criteria. SOX21 or SRY alone, or the panel of six SRY-related genes, could be used to estimate patient survival. SRY-related genes are positively correlated with immunological processes, as well as with keratinization and formation of the cornified envelope, and negatively correlated with DNA repair and response to stress. Moreover, except SRY, all analyzed genes were associated with a different tumor composition and immunological profiles. Based on validation results, the expression of SOX30 is higher in HPV(+) patients and is associated with patients' survival. SRY-related transcription factors have vast importance in HNSCC biology. SOX30 seems to be a potential biomarker of HPV infection and could be used as a prognostic marker, but further research is required to fully understand the role of SOX family genes in HNSCC.

Keywords: HNSCC; SOX2-OT; SOX21; SOX30; SOX6; SOX8; SRY; SRY-related transcription factors; TCGA; biomarker; long non-coding RNA; miRNA.

Grants and funding

This work was supported by Poznan University of Medical Sciences (Department of Cancer Immunology, Chair of Medical Biotechnology—budget for scientific activities) and by the Greater Poland Cancer Center grant no.: 1/2023(263), 13/01/2023/PGN/WCO/001.