| Abstrakt: |
Simple Summary: Poor survival rates of squamous cell carcinomas (SCCs) are due in part to a limited number of reliable biomarkers and molecular targets. NAD+ metabolism plays a relevant role in SCC chemoprevention and therapy and is found dysregulated in several tumors. Therefore, the aim of our study was to identify new biomarkers based on NAD+ metabolism-related gene (NMRG) expression. Our findings indicate that NAD+ metabolism-related gene profiles can be an important source of SCC biomarkers and potential therapeutic targets. These findings agree with SCC preclinical and clinical studies using NAD+ precursors. Further in-depth studies on identified NMRGs may provide additional insights into SCC pathogenesis and improve therapeutic choice. Poor survival rates of squamous cell carcinomas (SCCs) are associated with high recurrence, metastasis, and late diagnosis, due in part to a limited number of reliable biomarkers. Thus, the identification of signatures improving the diagnosis of different SCC types is mandatory. Considering the relevant role of NAD+ metabolism in SCC chemoprevention and therapy, the study aimed at identifying new biomarkers based on NAD+ metabolism-related gene (NMRG) expression. Gene expression of 18 NMRGs and clinical-pathological information for patients with head and neck SCC (HNSCC), lung SCC (LuSCC), and cervix SCC (CeSCC) from The Cancer Genome Atlas (TCGA) were analyzed by several bioinformatic tools. We identified a 16-NMRG profile discriminating 3 SCCs from 3 non-correlated tumors. We found several genes for HNSCC, LuSCC, and CeSCC with high diagnostic power. Notably, three NMRGs were SCC-type specific biomarkers. Furthermore, specific signatures displayed high diagnostic power for several clinical-pathological characteristics. Analyzing tumor-infiltrating immune cell profiles and PD-1/PD-L1 levels, we found that NMRG expression was associated with suppressive immune microenvironment mainly in HNSCC. Finally, the evaluation of patient survival identified specific genes for HNSCC, LuSCC, and CeSCC with potential prognostic power. Therefore, our analyses indicate NAD+ metabolism as an important source of SCC biomarkers and potential therapeutic targets. [ABSTRACT FROM AUTHOR] |
