Clinical significance and immune landscape of cuproptosis-related lncRNAs in kidney renal clear cell carcinoma: a bioinformatical analysis

Abstract

Background: Kidney renal clear cell carcinoma (KIRC) is considered an immunogenic tumor. Cuproptosis is a newly identified copper-induced regulated cell death that relies on mitochondria respiration. Long noncoding RNAs (lncRNAs) have emerged as significant players in tumorigenesis and metastasis. However, there is a huge knowledge gap on the prognostic role of cuproptosis-related lncRNAs in KIRC. And, the clinical value of them is still unknown. Here, we aimed to develop a cuproptosis-related lncRNA prognostic signature in KIRC. Methods:The messenger RNA (mRNA)/lncRNA expression profiles and the clinical information including age, gender, tumor stage, grade, and overall survival (OS) were acquired from The Cancer Genome Atlas (TCGA) database. The included KIRC samples were further randomly assigned into training (n=258) or testing (n=257) data sets. We performed Pearson correlation analysis to identify the cuproptosisrelated lncRNAs and then constructed the prognostic signature using Cox regression analysis and LASSO algorithm. Subsequently, Kaplan-Meier survival analysis, a nomogram, and receiver operating characteristic (ROC) curve were performed to assess the predictive performance of the signature. Moreover, the immune characteristics and drug sensitivity related to the signature were also explored. Results:The signature comprised 7 cuproptosis-related lncRNAs. The patients with a low-risk score had superior OS compared with those with a high-risk score. The survival rates of the high-and low-risk groups were 44.96% and 83.72% (P<0.001). The area under the curve (AUC) value for 1-, 3-, 5-year survival rate reached 0.814, 0.762 and 0.825, respectively. In addition, a nomogram was also generated; the AUC was 0.785 for risk score, higher than that for age (0.593), gender (0.489), grade (0.679), and stage (0.721). The highrisk group had more enriched immune-and tumor-related genes. Patients with low-risk scores were more sensitive to immunotherapy and the small molecular drugs GSK1904529A, tipifarnib, BX-912, FR-180204, and GSK1070916. Meanwhile, the high-risk group tended to be more sensitive to pyrimethamine, MS-275, and CGP-60474.Conclusions: Collectively, we constructed a cuproptosis-related lncRNA prognostic signature with a higher predictive accuracy compared to multiple clinicopathological parameters, which may provide vital guidance for therapeutic strategies in KIRC. Combination of more prognostic biomarkers may further improve the accuracy.

Characterization of tumor microenvironment and sensitive chemotherapy drugs based on cuproptosis-related signatures in renal cell carcinoma

“…Li et al found that patients with low PIK3CA expression had poorer overall survival, and the AUC of their ROC curve was 0.775 [ 45 ]. Li et al found that the area under the curve (AUC) values of 1-year, 3-year and 5-year survival rates of the model constructed with seven cuproptosis-related genes were 0.814, 0.762 and 0.825, respectively [ 46 ]. Li et al constructed six-gene biomarkers (ARPC3, PHF19, FKBP11, MS4A14, KDELR3 and CD1C) to predict the 1-year, 3-year and 5-year efficacy of 0.911, 0.845 and 0.867 (AUC), respectively.…”

Mild intellectual disability and borderline intellectual functioning in two sisters with a 12p11.22 loss: A case report

“…OVCH1-AS1 (OVCH1 antisense RNA 1) is produced from the antisense strand of OVCH1, which may have the opposite impact. Its involvement has been reported in hepatocellular carcinoma (44) and kidney renal clear cell carcinoma (45). TMTC1 (transmembrane O-mannosyltransferase targeting cadherins) is one of four TMTC members, originally identi ed as an endoplasmic reticulum protein involved in calcium homeostasis.…”

“…Intellectual disability (ID) is characterized by signi cant impairments in both intellectual and adaptive functioning, which refers to the ability to learn, reason, and solve problems, and functioning in conceptual, social, and practical domains (1). According to intelligence quotient (IQ) scores, severity is classi ed into mild (IQ 50-69), moderate (IQ [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49], severe (IQ [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] and profound (IQ 0-19). Between 1% and 3% of the global population is affected by this type of developmental disorder (2,3); of all cases, approximately 85% are classi ed as having mild severity (4).…”

Construction of a five-disulfidptosis-related-lncRNA signature for predicting prognosis and immune activity in kidney renal clear cell carcinoma

“…Chen et al established a prognostic nomogram based on ve m6A-related lncRNAs to predict the overall survival of patients with KIRC and examined the biological functions of m6A-related lncRNAs [18]. Zhang et al constructed a prognostic signature comprising seven cuproptosisrelated lncRNAs that had higher predictive e ciency than clinicopathological parameters and further examined immune characteristics and drug sensitivity [19]. In addition, necrosis-, autophagy-and hypoxia-related lncRNA models have been constructed to predict the prognosis of KIRC [20][21][22], providing important guidance for treatment.…”