Prognostic model and immunotherapy prediction based on molecular chaperone-related lncRNAs in lung adenocarcinoma

Introduction: Molecular chaperones and long non-coding RNAs (lncRNAs) have been confirmed to be closely related to the occurrence and development of tumors, especially lung cancer. Our study aimed to construct a kind of molecular chaperone-related long non-coding RNAs (MCRLncs) marker to accurately predict the prognosis of lung adenocarcinoma (LUAD) patients and find new immunotherapy targets.

Methods: In this study, we acquired molecular chaperone genes from two databases, Genecards and molecular signatures database (MsigDB). And then, we downloaded transcriptome data, clinical data, and mutation information of LUAD patients through the Cancer Genome Atlas (TCGA). MCRLncs were determined by Spearman correlation analysis. We used univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis to construct risk models. Kaplan-meier (KM) analysis was used to understand the difference in survival between high and low-risk groups. Nomogram, calibration curve, concordance index (C-index) curve, and receiver operating characteristic (ROC) curve were used to evaluate the accuracy of the risk model prediction. In addition, we used gene ontology (GO) enrichment analysis and kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses to explore the potential biological functions of MCRLncs. Immune microenvironmental landscapes were constructed by using single-sample gene set enrichment analysis (ssGSEA), tumor immune dysfunction and exclusion (TIDE) algorithm, “pRRophetic” R package, and “IMvigor210” dataset. The stem cell index based on mRNAsi expression was used to further evaluate the patient’s prognosis.

Results: Sixteen MCRLncs were identified as independent prognostic indicators in patients with LUAD. Patients in the high-risk group had significantly worse overall survival (OS). ROC curve suggested that the prognostic features of MCRLncs had a good predictive ability for OS. Immune system activation was more pronounced in the high-risk group. Prognostic features of the high-risk group were strongly associated with exclusion and cancer-associated fibroblasts (CAF). According to this prognostic model, a total of 15 potential chemotherapeutic agents were screened for the treatment of LUAD. Immunotherapy analysis showed that the selected chemotherapeutic drugs had potential application value. Stem cell index mRNAsi correlates with prognosis in patients with LUAD.

Conclusion: Our study established a kind of novel MCRLncs marker that can effectively predict OS in LUAD patients and provided a new model for the application of immunotherapy in clinical practice.