Clinicopathological Implication of Long Non-Coding RNAs SOX2 Overlapping Transcript and Its Potential Target Gene Network in Various Cancers.

BACKGROUND

SOX2 overlapping transcript (SOX2-OT) produces alternatively spliced long non-coding RNAs (lncRNA). Previous studies of the prognostic role of SOX2-OT expression met with conflicting results. The aim of this study was to properly consider the prognostic role of SOX2-OT expression in several cancers. In addition, the regulative mechanism of SOX2-OT is explored.

METHODS

PubMed, EMBASE, and Cochrane Library and The Cancer Genome Atlas (TCGA) database were comprehensively explored to recover pertinent studies. We conducted an extensive inquiry to verify the implication of SOX2-OT expression in cancer patients by conducting a meta-analysis of 13 selected studies. Thirty-two TCGA databases were used to analyze the connection between SOX2-OT expression and both the overall survival (OS) and clinicopathological characteristics of cancer patients using R and STATA 13.0. Trial sequential analysis (TSA) was adopted in order to compute the studies' power.

RESULTS

Thirteen studies involving 1172 cancer patients and 32 TCGA cancer types involving 9676 cancer patients were eventually selected. Elevated SOX2-OT expression was significantly related to shorter OS (HR = 2.026, 95% CI: 1.691-2.428, < 0.0001) and disease-free survival (DFS) (HR = 2.554, 95% CI: 1.261-5.174, = 0.0092) in cancer patients. Meanwhile, TSA substantiated adequate power to demonstrate the relationship between SOX2-OT expression and OS. The cancer patients with elevated SOX2-OT expression were more likely to have advanced clinical stage (RR = 1.468, 95% CI: 1.106-1.949, = 0.0079), earlier lymphatic metastasis ( = 0.0005), earlier distant metastasis ( < 0.0001), greater tumor size ( < 0.0001), and more extreme tumor invasion ( < 0.0001) compared to those with low SOX2-OT expression. Meta-regression and subgroup analysis revealed that follow-up time, sample type, and tumor type could significantly contribute to heterogeneity for survival outcomes. The follow-up time could significantly explain heterogeneity for tumor, node, metastasis (TNM) stage. Furthermore, up to 500 validated target genes were distinguished, and the gene oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses demonstrated that the validated targets of SOX2-OT were substantially enriched in cell adhesion, mRNA binding, and mRNA surveillance pathways.

CONCLUSIONS

Elevated expression of SOX2-OT predicted a poor OS and DFS. Overexpression of SOX2-OT was correlated with more advanced tumor stage, earlier lymphatic metastasis, earlier distant metastasis, larger tumor size, and deeper tumor invasion. SOX2-OT-mediated cell adhesion, mRNA binding, or mRNA surveillance could be intrinsic mechanisms for invasion and metastasis.