A seven-LncRNA signature for prognosis prediction of patients with lung squamous cell carcinoma through tumor immune escape.

Abstract

Background: Lung squamous cell carcinoma (LUSC) is a malignant disease associated with poor therapeutic responses and prognosis. Preliminary studies have shown that the dysregulation of long non-coding RNAs (LncRNAs) is linked to cancer development and prognosis. However, research on the role of LncRNAs in LUSC remains limited.

Methods: In this study, we aimed to develop a LncRNA signature for improved prognostic prediction in LUSC and to elucidate the underlying mechanisms. We utilized expression data of LncRNAs and clinical information from 471 LUSC patients in The Cancer Genome Atlas (TCGA), randomly dividing them into a training set (n=236) and a testing set (n=235).

Results: A prognostic signature model comprising seven LncRNAs was constructed using multivariate Cox regression analysis based on the training set. Using a risk score cutoff value of -0.12 (log2-transformed), patients were categorized into high-risk (n=101) and low-risk (n=370) groups. The high-risk group demonstrated significantly worse overall survival (OS) compared to the low-risk group (p<0.0001). The risk score showed strong prognostic predictive ability for LUSC patients, as evidenced by the area under the ROC curve (AUC: 0.66, 0.67, and 0.67) and nomogram analysis (C-index, calibration, and decision curve analysis) for 1-, 3-, and 5-year survival predictions. Independent prognostic factors for LUSC were identified, including risk group (HR=0.3, 95% CI: 0.22-0.4), stage (HR=1.78, 95% CI: 1.28-2.48), and age (HR=1.02, 95% CI: 1.00-1.04). KEGG enrichment analysis revealed that mRNAs influenced by the seven targeted LncRNAs, associated with immune evasion, were primarily linked to pathways such as chemical carcinogenesis, Th17 cell differentiation, NF-κB signaling, and proteoglycans in cancer. Expression levels of 14 target genes related to tumor immune tolerance were significantly suppressed, with eight confirmed via real-time PCR and western blot analysis. Additionally, CIBERSORT analysis of immune cell-related gene expression between normal and LUSC tissues indicated activation of the immune system in LUSC patients.

Conclusion: In conclusion, our findings highlight the clinical significance of the seven LncRNA signature in predicting survival outcomes for LUSC patients.