Cancer Management and Research (Feb 2023)
Identification of Immune-Related Seven-Long Non-Coding RNA Signature for Overall Survival and Validation of the Effect of LINC01270 in Malignant Phenotypes of Clear Cell Renal Carcinoma
Abstract
Chengxuan Liu,1 Weijian Xiong,1 Jing Song,2 Xiaoqin Ouyang,1 Yang Fu3 1Department of Nephrology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, People’s Republic of China; 2Molecular Medicine and Cancer Research Centre, Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Rehabilitation, Chongqing Traditional Chinese medicine Hospital, Chongqing, People’s Republic of ChinaCorrespondence: Yang Fu, Department of Rehabilitation, Chongqing Traditional Chinese Medicine Hospital, No. 6 Panxi Branch Road, Jiangbei District, Chongqing, 400021, People’s Republic of China, Email [email protected]: The overall survival of patients with high-stage clear cell renal carcinoma (ccRCC) is poor. However, promising molecular-level prognostic marker is still lacking to date.Methods: We systematically evaluated the prognostic potential of immune-related long non-coding RNAs (lncRNAs) in ccRCC. The expressions of lncRNAs were validated in clinical tissues of ccRCC. Functional experiments were performed to investigate the role of lncRNAs in ccRCC.Results: Eight hundred and ninety-three lncRNAs were differentially expressed in ccRCC and compared with normal controls and were screened out using three independent cohorts. Among them, 290 immune-related lncRNAs were identified. We identified a seven-lncRNA signature (LINC01270, FIRRE, RP11-37B2.1, RP11-253I19.3, RP11-438L19.1, RP11-504P24.9, and CTB-41I6.1) associated with the overall survival of late-stage ccRCC patients. Further multivariate Cox analysis using clinical factors as covariates showed that our lncRNA signature was an independent biomarker in training (P < 0.001, Log rank test) and validation cohorts (P = 0.003). The seven lncRNAs were closely related to the major targets (PD-1, PD-L1, and CTLA4) of immune checkpoint blockade drugs, implying that they may have potential value in predicting immunotherapy response. The seven lncRNAs may play an important role in tumor-infiltrating immune cells (eg, T/B cells) and tumor progression through regulating the binding of protein receptors/complexes, as revealed by functional analysis. qRT-PCR showed that LINC01270 was upregulated in ccRCC tissues (n=20) compared with paired normal samples. Functional experiments showed that LINC01270 silencing inhibited the proliferation, invasion, and migration of ccRCC cells.Discussion: In summary, the seven-lncRNA signature has great potential in prognosis for patients with late-stage ccRCC, which could be a novel clinical biomarker. LINC01270 could be a novel therapeutic target of ccRCC.Keywords: long non-coding RNA FIRRE, prognosis, renal cell carcinoma, tumor immune
