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.
Highlights
Kidney cancer is one of the 10 most common cancers around the world, accounting for about 2% of all global cancer cases, and the number of cases is rising year by year [1]
Renal cell carcinoma (RCC), which originates from the renal epithelium, accounts for >90% of the malignant tumors happening in the kidney and has numerous histological subtypes, among which clear cell renal cell carcinoma is the most common and accounts for about three quarters of all cases [5]
Since it was reported that Long noncoding RNAs (lncRNAs) may affect the tumor immune cell microenvironment by regulating tumor immune cell infiltration [14], we explored the relationship between the risk model and the tumor immune cell microenvironment in the step
Summary
Kidney cancer is one of the 10 most common cancers around the world, accounting for about 2% of all global cancer cases, and the number of cases is rising year by year [1]. 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. 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 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. 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. This signature was proven to have a potential predictive significance for the prognosis of patients with ccRCC and the efficacy of immunotherapy
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