Liu Chengxuan, Xiong Weijian, Song Jing, Ouyang Xiaoqin, Fu Yang
Department of Nephrology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, People's Republic of China.
Molecular Medicine and Cancer Research Centre, Chongqing Medical University, Chongqing, People's Republic of China.
Cancer Manag Res. 2023 Feb 14;15:131-145. doi: 10.2147/CMAR.S394100. eCollection 2023.
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.
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.
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.
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.
晚期透明细胞肾细胞癌（ccRCC）患者的总体生存率较低。然而，迄今为止仍缺乏有前景的分子水平预后标志物。
我们系统评估了免疫相关长链非编码RNA（lncRNAs）在ccRCC中的预后潜力。在ccRCC临床组织中验证了lncRNAs的表达。进行功能实验以研究lncRNAs在ccRCC中的作用。
893个lncRNAs在ccRCC中与正常对照相比存在差异表达，并使用三个独立队列进行筛选。其中，鉴定出290个免疫相关lncRNAs。我们鉴定出一个与晚期ccRCC患者总体生存相关的七lncRNA特征（LINC01270、FIRRE、RP11 - 37B2.1、RP11 - 253I19.3、RP11 - 438L19.1、RP11 - 504P24.9和CTB - 41I6.1）。使用临床因素作为协变量的进一步多变量Cox分析表明，我们的lncRNA特征在训练队列（P < 0.001，对数秩检验）和验证队列（P = 0.003）中是一个独立的生物标志物。这七个lncRNAs与免疫检查点阻断药物的主要靶点（PD - 1、PD - L1和CTLA4）密切相关，这意味着它们在预测免疫治疗反应方面可能具有潜在价值。功能分析显示，这七个lncRNAs可能通过调节蛋白质受体/复合物的结合在肿瘤浸润免疫细胞（如T/B细胞）和肿瘤进展中起重要作用。qRT - PCR显示，与配对的正常样本相比，LINC01270在ccRCC组织（n = 20）中上调。功能实验表明，LINC01270沉默抑制了ccRCC细胞的增殖、侵袭和迁移。
总之，七lncRNA特征在晚期ccRCC患者的预后评估中具有巨大潜力，可能是一种新型临床生物标志物。LINC01270可能是ccRCC的新型治疗靶点。
