Abstract
Kidney renal clear cell carcinoma (KIRC) is the predominant pathological subtype of renal cell carcinoma (RCC) in adults. Long non-coding RNAs (lncRNAs) are an important class of gene expression regulators and serve fundamental roles in immune regulation. The intent of this study is to develop a novel immune-related lncRNA signature to accurately predict the prognosis for KIRC patients. Here, we performed genome-wide comparative analysis of lncRNA expression profiles in 537 KIRC patients from The Cancer Genome Atlas (TCGA) database. Cox regression model–identified immune-related lncRNAs were extracted for constructing a novel five immune-related lncRNA signature (AC008105.3, LINC02084, AC243960.1, AC093278.2, and AC108449.2) with the ability to predict the prognosis of KIRC patients. Univariate and multivariate Cox regression analyses demonstrated that the signature could act as an independent prognostic predictor for overall survival (OS). With the further investigation on different clinicopathological parameters, we found that the signature could divide KIRC samples into high-risk groups with shorter OS and low-risk groups with longer OS in different subgroups. Principal component analysis suggested that the five immune-related lncRNA signature drew a clear distinction between high- and low-risk groups based on the immune-related lncRNAs. The different immune status between the two groups was observed in gene set enrichment analysis and the ESTIMATE algorithm. Except for AC093278.2, the expressions of the other four lncRNAs expression were significantly upregulated in tumor tissues. In summary, the identified immune-lncRNA signature had important clinical implications in prognosis prediction and could be exploited as underlying immune therapeutic targets for KIRC patients.
Highlights
Renal cell carcinoma (RCC), accounting for ∼2% of adult malignancies, is the third most common malignant tumor of the urinary system worldwide following prostate and bladder cancer [1]
A total of 15,142 Long non-coding RNAs (lncRNAs) as well as their expression profiles were screened from the The Cancer Genome Atlas (TCGA) data sets, and the list of 332 immunoregulatory genes was downloaded from the Molecular Signatures Database
We carried out univariate Cox regression analysis to further single out the potential prognostic lncRNAs from the cohort of immune-related lncRNAs and found that 12 lncRNAs were significantly related with the Kidney renal clear cell carcinoma (KIRC) patients’ overall survival (OS) (P < 0.01, Figure 1A)
Summary
Renal cell carcinoma (RCC), accounting for ∼2% of adult malignancies, is the third most common malignant tumor of the urinary system worldwide following prostate and bladder cancer [1]. Kidney renal clear cell carcinoma (KIRC) is the predominant pathological subtype and represents ∼90% of the total cases of RCC in adults [2]. Since the clinical symptoms and signs of early stage RCC are often insidious and non-specific, a great proportion of patients are not diagnosed until. Immune-Related lncRNA Signature for KIRC advanced tumor stages [3]. The 5-year overall survival (OS) rate for patients with early stage RCC is up to 90% OS of those with locally advanced RCC and metastatic RCC could drop to 60 and 10%, respectively [5].
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