Sex determining region Y box protein 2 (SOX2) expression, alteration, regulation and its diagnostics, prognostics and therapeutics in lung cancer

Lung cancer is the leading cause of cancer death in China and worldwide. Sex determining region Y box protein 2 (SOX2) is involved in pluripotency regulation in embryonic stem cells, morphogenesis, and homeostasis of tracheobronchial epithelia, as well as cancer. Given its oncogenic potential, this study aimed to investigate the potential of SOX2 as a biomarker and evaluate the inhibitory effects of cordycepin (CD), a natural compound, on SOX2-driven oncogenic phenotypes in lung cancer. In this study, by analyzing TCGA and UALCAN datasets together with Chinese patient samples, we found that SOX2 was highly expressed at both the mRNA and protein levels in LUSC. In LUAD, SOX2 mRNA levels were unchanged, whereas SOX2 protein levels were decreased. High SOX2 expression was significantly associated with poorer patient survival (including OS, FPS, DSS, and DFS), regardless of whether it was mutated or not. SOX2 alterations were mainly amplifications in cancers, including that LUSC is the highest (40.04% in all cases), and in LUAD is only the 14th highest (2.58% in all cases) among all cancers, implying that LUSC SOX2 showed high gene amplification that could affect gene expression. Moreover, overexpression of SOX2 promoted lung cancer cell growth, migration, and invasion, while CD, a natural product originally from the traditional Chinese medicine Cordyceps sinensis (BerK.), suppressed SOX2-mediated progression, including the growth, migration, and invasion of lung cancer. Taken together, these results implied that SOX2 is a potential biomarker for diagnostics, prognostics, and therapeutics for lung cancer, including LUAD and LUSC.