Chromatin regulators-related lncRNA signature predicting the prognosis of kidney renal clear cell carcinoma and its relationship with immune microenvironment: A study based on bioinformatics and experimental validation

Abstract

Background: Kidney Renal Clear cell carcinoma (KIRC) is a major concern in the urinary system. A lot of researches were focused on Chromatin Regulators (CRs) in tumors. In this study, CRs-related lncRNAs (CRlncRNAs) were investigated for their potential impact on the prognosis of KIRC and the immune microenvironment. Methods: The TCGA database was used to obtain transcriptome and related clinical information. CRs were obtained from previous studies, whereas CRlncRNAs were obtained by differential and correlation analysis. We screened the lncRNAs for the signature construction using regression analysis and LASSO regression analysis. The effectiveness of the signature was evaluated using the Kaplan-Meier (K-M) curve and Receiver Operating Characteristic curve (ROC). Additionally, we examined the associations between the signature and Tumor Microenvironment (TME), and the efficacy of drug therapy. Finally, we further verified whether these lncRNAs could affect the biological function of KIRC cells by functional experiments such as CCK8 and transwell assay. Results: A signature consisting of 8 CRlncRNAs was constructed to predict the prognosis of KIRC. Quantitative Real-Time PCR verified the expression of 8 lncRNAs at the cell line and tissue level. The signature was found to be an independent prognostic indicator for KIRC in regression analysis. This signature was found to predict Overall Survival (OS) better for patients in the subgroups of age, gender, grade, stage, M, N0, and T. Furthermore, a significant correlation was found between riskScore and immune cell infiltration and immune checkpoint. Finally, we discovered several drugs with different IC50 values in different risk groups using drug sensitivity analysis. And functional experiments showed that Z97200.1 could affect the proliferation, migration and invasion of KIRC cells. Conclusion: Overall, the signature comprised of these 8 lncRNAs were reliable prognostic biomarkers for KIRC. Moreover, the signature had significant potential for assessing the immunological landscape of tumors and providing individualized treatment.