Association between SOX gene family expression, DNA methylation, and miRNA regulation in lung adenocarcinoma progression.

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. Upregulation of SOX8 and SOX17 is associated with improved outcomes in LUAD patients (HR < 1, log-rank P < 0.05), whereas high expression of SOX3, SOX5, SOX6, SOX12, SOX14, SOX15, SOX18, and SRY correlates with poor prognosis in LUAD patients (HR > 1, log-rank P < 0.05). The mRNA expression of SOX3 and SOX15 was significantly higher in LUAD tissues compared to adjacent normal tissues, while SOX5, SOX6, SOX12, SOX17, SOX18, and SRY were lower in LUAD tissues than in adjacent normal tissues (P < 0.05). Moreover, SOX3, SOX5, SOX8, SOX14, SOX17 and SOX18 showed hypermethylation, while SOX15 showed hypomethylation in LUAD tissues (P < 0.05). Furthermore, hsa-miR-1-3p and miR-499a-5p were positively correlated with SOX5 (r = 0.272, P = 3.87 × 10) and SOX6 (r = 0.109, P = 1.34 × 10), respectively.

Conclusion: The SOX gene family is closely implicated in the onset and progression of lung adenocarcinoma, of which most members may be used as prognostic marker genes for patients.