Prognostic lncRNAs and their functional pathways in gastric cancer revealed by bioinformatics and experimental validation.

BACKGROUND

Long non-coding RNAs (lncRNAs) are dysregulated in many malignancies, including gastric cancer, where they may act as oncogenes or tumour suppressors. This study examined six lncRNAs-SLC12A5-AS1, MAP3K2-DT, LINC02544, MIR181A2HG, LINC01914 and LNCOG-in gastric cancer and the pathways associated with them.

METHODS

Expression was analysed in TCGA-STAD (412 tumour, 36 normal samples). Prognostic value was assessed by univariable and multivariable Cox regression and Kaplan-Meier analysis. Co-expression networks and pathway enrichment identified associated processes. Findings were validated by RT-qPCR in 25 paired clinical specimens.

RESULTS

All six lncRNAs were significantly upregulated in tumour tissue, with fold changes of 1.6 to 6.6 (FDR 2.0 × 10⁻² to 4.2 × 10⁻¹¹). ROC analysis gave AUC values of 0.650 to 0.910, with LINC01914, LNCOG and LINC02544 exceeding 0.8. Higher expression of all six was associated with unfavourable overall survival; after adjustment for pathological stage, age and sex the association remained significant for LNCOG (HR 1.23, P = 0.013), LINC02544 (HR 1.17, P = 0.021) and SLC12A5-AS1 (HR 1.17, P = 0.039). Co-expression enrichment identified several cancer-associated pathways, most prominently epithelial-mesenchymal transition.

CONCLUSION

These six lncRNAs may have diagnostic and prognostic value in gastric cancer. LINC01914 (AUC 0.910), LNCOG (AUC 0.893) and LINC02544 (AUC 0.835) showed the strongest discriminatory performance. These findings are preliminary and require independent validation in larger cohorts before any clinical diagnostic application can be inferred.