A novel pyroptosis-related lncRNA prognostic signature associated with the immune microenvironment in lung squamous cell carcinoma

Abstract

Background: A growing body of evidence suggests that pyroptosis-related lncRNAs (PRncRNAs) are associated with the prognoses of tumor patients and their tumor immune microenvironments. However, the function of PRlncRNAs in lung squamous cell carcinoma (LUSC) remains unclear.

Methods: We downloaded the transcriptome and clinical information of 551 LUSC samples from the The Cancer Genome Atlas (TCGA) database and randomly separated patients with complete information into two cohorts. Based on the training cohort, we developed a pyroptosis-related signature. We then examined the signature in the test cohort and all retained patients. We also clustered two risk groups in each cohort according to the signature and performed survival analysis, functional analysis, tumor immune microenvironment analysis and drug sensitivity analysis.

Results: A prognostic signature containing five PRlncRNAs (AP001189.1, PICART1, LINC02555, AC010422.4, and AL606469.1) was developed. A principal component analysis (PCA) indicated better differentiation between patients with different risk scores. Kaplan-Meier (K-M) analysis demonstrated poorer survival among patients with higher risk scores (P < 0.001). A receiver operating characteristic (ROC) curve analysis provided evidence confirming the accuracy of the signature, and univariate (p = 0.005) and multivariate (p = 0.008) Cox regression analyses confirmed the independent value of the risk score in prognoses. Clinical subgroup validation indicated that the signature was more suitable for patients with early-stage LUSC. We also created a nomogram to increase the accuracy of the prediction. Moreover, functional analysis revealed that pathways related to tumor development and pyroptosis were enriched in the high-risk group. Furthermore, the prognostic signature was proven to be a predictor of sensitivity to immunotherapy and chemotherapy.

Conclusions: We developed a novel pyroptosis-associated signature with independent value for the prognosis of LUSC patients. PRlncRNAs are closely associated with the tumor immune microenvironment in LUSC and might offer new directions for immunotherapy.

Keywords: Immunotherapy; Long non-coding RNA; Lung squamous cell carcinoma; Prognostic signature; Pyroptosis.