Construction of a Novel kidney renal clear cell carcinoma microenvironment-related lncRNA pair Signature

Abstract

Background: Kidney Renal clear cell carcinoma (KIRC) is a malignant neoplasm originating in the tubular epithelium and is the most common pathologic type of renal carcinoma, accounting for approximately 80% of cases. Tumor microenvironment (TME) has been proved to play a key role in the development of tumor, including KIRC. A number of studies have focused on tumor TME-related genes, but have ignored the key role of TME-related lncRNAs in disease. Method:In this article, we obtained 6 TME-related genes by using ESTIMATE and CIBERSORT computational methods from 611 cases which are downloaded from the TCGA Kidney Renal Clear Cell Carcinoma database. And then we performed coexpression analysis between 6 TME-related genes and lncRNAs to find differently expressed TME-related lncRNAs(TMErlncRNAs). The matrix of TMErlncRNA pairs was established by a cyclic comparison of each lncRNA pair expression level. Univariate and multivariate Cox regressions and LASSO regression analysis were used to construct the hazard model. We have sifted 10 lncRNA pairs that were included in this model. TCGA cohort was divided into high- and low-risk groups, according to the Akaike Information Criterion (AIC) values of the receiver operating characteristic (ROC) curve. Then, we tested and verified our model through various clinical settings: tumor-infiltrating immune cells, clinical-pathological characteristics and reactiveness to immunotherapy. Results: Based on the 6 differently expressed TME-related genes, we sifted and constructed a 10-TME-related lncRNA pair signature. The area under the receiver operator characteristic (ROC) curve (AUC) of the signature was 0. 766, showing a promising prediction value for KIRC, and the cut-off point was recognized as 0. 862. Subsequent analysis showed that our signature is closely associated with clinical pathological characteristics, overall survival, specify tumor infiltration status, and reactiveness to immunotherapy in patients with KIRC. Conclusion: We constructed a novel kidney renal clear cell carcinoma TME-related lncRNA pair signature with promising clinical prediction value in KIRC, which might provide new insights for clinical decision-making and precision medicine.