Construction of a Novel Immune-Related lncRNA Pair Signature with Prognostic Significance for Kidney Clear Cell Renal Cell Carcinoma

Abstract

Background. Renal cell carcinoma (RCC) is one of the most common aggressive malignant tumors in the urinary system, among which the clear cell renal cell carcinoma (ccRCC) is the most common subtype. The immune-related long noncoding ribonucleic acids (irlncRNAs) which are abundant in immune cells and immune microenvironment (IME) have potential significance in evaluating the prognosis and effects of immunotherapy. The signature based on irlncRNA pairs and independent of the exact expression level seems to have a latent predictive significance for the prognosis of patients with malignant tumors but has not been applied in ccRCC yet. Method. In this article, we retrieved The Cancer Genome Atlas (TCGA) database for the transcriptome profiling data of the ccRCC and performed coexpression analysis between known immune-related genes (ir-genes) and lncRNAs to find differently expressed irlncRNA (DEirlncRNA). Then, we adopted a single-factor test and a modified LASSO regression analysis to screen out ideal DEirlncRNAs and constructed a Cox proportional hazard model. We have sifted 28 DEirlncRNA pairs, 12 of which were included in this model. Next, we compared the area under the curve (AUC), found the cutoff point by using the Akaike information criterion (AIC) value, and distinguished the patients with ccRCC into a high-risk group and a low-risk group using this value. Finally, we tested this model by investigating the relationship between risk score and survival, clinical pathological characteristics, cells in tumor immune microenvironment, chemotherapy, and targeted checkpoint biomarkers. Results. A novel immune-related lncRNA pair signature consisting of 12 DEirlncRNA pairs was successfully constructed and tightly associated with overall survival, clinical pathological characteristics, cells in tumor immune microenvironment, and reactiveness to immunotherapy and chemotherapy in patients with ccRCC. Besides, the efficacy of this signature was verified in some commonly used clinicopathological subgroups and could serve as an independent prognostic factor in patients with ccRCC. Conclusions. This signature was proven to have a potential predictive significance for the prognosis of patients with ccRCC and the efficacy of immunotherapy.

N7-methylguanosine-related lncRNAs: Distinction between hot and cold tumors and construction of predictive models in colon adenocarcinoma

“…The immune correlation heatmap showed the distribution of immune cells in different clusters. CD8+ T cells from TIMER, CIBERSORT-ABS, QUANTISEQ, and XCELL had significantly more infiltration in Cluster2 ( Supplementary Table 3 ; Supplementary Figure 1B ) ( 24 ). Several immune checkpoints were significantly higher in Cluster2 than Cluster1, specifically PD1, PD-L1, CTL4, LAG3, and TIM3 ( Figure 2F ).…”

Robust Prediction of Prognosis and Immunotherapeutic Response for Clear Cell Renal Cell Carcinoma Through Deep Learning Algorithm

“…As a revolutionary therapy, immunotherapy has shown its improvement in prolonging the survival of various malignant tumors, including lung cancer, gastric cancer, bladder cancer, and melanoma. Moreover, some studies illustrated that ICIs could obviously increase the survival of intermediate-or poor- risk metastatic ccRCC patients with fewer adverse reactions (36,37). However, as a common issue for immunotherapies, only limited ccRCC patients could receive therapeutic benefits from ICIs.…”

Systematic Investigation of Immune-Related lncRNA Landscape Reveals a Potential Long Non-Coding RNA Signature for Predicting Prognosis in Renal Cell Carcinoma

“…Dong et al identified a redox-related lncRNA signature of RCC and the AUC value was 0.82 ( Qi-Dong et al, 2020 ). Sun et al constructed an immune-related lncRNA pair signature of RCC and the AUC value was 0.76 ( Sun et al, 2021 ). In our prognostic model, we constructed a tumorigenesis-related and immune infiltration-related lncRNA signature for predicting the prognosis of RCC, with an AUC value of 0.9.…”

“…Recent studies have reported several prognostic models for RCC. However, the Area Under Curve (AUC) values were all less than 0.83 (Qi-Dong et al, 2020;Ma et al, 2021;Sun et al, 2021;Yu et al, 2021). Therefore, a more efficient model is urgently needed for predicting the prognosis of RCC.…”