AUTHOR=Xie Tongjin , Liu Bin , Liu Dongbo , Zhou Yusong , Yang Qingping , Wang Dai , Tang Mengjie , Liu Wei TITLE=Cuproptosis-related lncRNA signatures predict prognosis and immune relevance of kidney renal papillary cell carcinoma JOURNAL=Frontiers in Pharmacology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1103986 DOI=10.3389/fphar.2022.1103986 ISSN=1663-9812 ABSTRACT=

Kidney renal papillary cell carcinoma (KIRP) has a high mortality rate and a poor prognosis. Cu concentrations differed significantly between renal cancer tissues and adjacent normal tissues. Cuproptosis is a newly identified cell death. Long non-coding RNAs (lncRNAs) play a crucial role in the progression of KIRP. In this study, we focused on constructing and validating cuproptosis-related lncRNA signatures to predict the prognosis of KIRP patients and their immune correlation. We created prognosis models using Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) algorithm. We found that patients in the high-risk group had poorer overall survival (OS) and progression-free survival (PFS) and higher mortality. Risk score and stage are prognosis factors independent of other clinical features. Kaplan-Meier analysis, receiver operating characteristic (ROC) curves, and C-index curves showed that cuproptosis-related lncRNA signatures could more accurately predict the prognosis of patients. Functional enrichment analysis suggests that the function of differentially expressed genes (DEGs) is associated with KIRP development and immunity. In immune-related function analysis, we found a significant difference in parainflammation responses between high-risk and low-risk groups. The mutation frequencies of TTN, MET, KMT2C, PKHD1, SETD2, and KMT2D genes in the high-risk group were higher than those in the low-risk group, but the mutation frequencies of MUC16, KIAA109, CUBN, USH2A, DNAH8 and HERC2 genes were significantly lower than those in the low-risk group. Survival analysis of tumor mutation burden (TMB) and combined TMB-risk showed better OS in patients with high TMB. Immune infiltration and immune checkpoint analysis assessed the immune association of six high mutation frequency genes (TTN, MET, KMT2C, PKHD1, SETD2, and KMT2D) with KIRP. Finally, we performed a drug sensitivity analysis and screened 15 potential drugs that differed between high-risk and low-risk patients. In this study, we constructed and validated cuproptosis-related lncRNA signatures that can more accurately predict the prognosis of KIRP patients and provide new potential therapeutic targets and prognosis markers for KIRP patients.