Analysis of SOX gene family expression and prognostic significance in lung adenocarcinoma based on tumor databases

Abstract

Abstract Objective To analyze the expression of the SOX gene family in lung adenocarcinoma and its impact on the prognosis of lung adenocarcinoma patients using tumor databases. Methods The cBioPortal database was used to retrieve and analyze the mutation frequencies and variants of 10 genes in the SOX gene family in lung adenocarcinoma tissues. Using clinical information from the Kaplan-Meier plotter database, the potential prognostic values of 10 genes in the SOX gene family in lung adenocarcinoma patients were further explored. The UALCAN database and TCGA database were used to obtain the expression of methylation of SOX gene family members and compare the mRNA expression of 10 genes in lung adenocarcinoma tissues and paracancerous tissues, respectively. The miRCancer database was intersected with miRTarBase, ENCORI, and miRWalk databases to find the lung adenocarcinoma-related miRNAs that regulate the SOX gene family. Results Most members in the SOX gene family had expansion mutation, but SOX15 had a deletion mutation. The expressions of SOX8 and SOX17 genes were upregulated in lung adenocarcinoma patients (HR < 1, log-rank P < 0.05), which was beneficial to their prognosis. In addition, SOX3, SOX5, SOX6, SO12, SOX14, SOX15, SOX18 and SRY genes were all significantly downregulated in lung adenocarcinoma patients (HR > 1, log-rank P < 0.05), suggesting that their high expression was associated with poor prognosis. The expressions of SOX5, SOX6, SOX12, SOX17, SOX18 and SRY in lung adenocarcinoma tissues were lower than those in paraneoplastic tissues (P < 0.05). The mRNA expression of the SOX15 gene in lung adenocarcinoma tissues was significantly higher than that in paracancerous tissues (P < 0.05). Moreover, SOX3, SOX5, SOX8, SOX14, SOX17 and SOX18 showed hypermethylation, while SOX15 and SRY showed hypomethylation in lung adenocarcinoma tissues, and the difference was statistically significant (P < 0.05). The low expressions of SOX5, SOX17, and SOX18 were correlated with their promoter region hypermethylation, suggesting that their methylation may also play a role in the occurrence and development of lung adenocarcinoma. Furthermore, hsa-miR-1-3p and miR-499a-5p were positively correlated with SOX5 (r = 0.272, p = 3.87x10− 10) and SOX6 (r = 0.109, p = 1.34x10− 2), respectively. Conclusion The SOX gene family is closely implicated in the onset and progression of lung adenocarcinoma, of which most members can be used as prognostic marker genes for tumor patients.