Liu Ying, Luo Jian, Zeng Jing, Liu Weipeng, Fu Bin, Xiong Jing
Department of Preventive Medicine, School of Public Health, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
Department of Laboratory Medicine, The First People's Hospital of Yichang, The People's Hospital of China Three Gorges University, Yichang, Hubei 443000, P.R. China.
Oncol Lett. 2023 May 22;26(1):290. doi: 10.3892/ol.2023.13876. eCollection 2023 Jul.
Distant metastasis is the main cause of death in patients with clear cell renal carcinoma (ccRCC). The dysregulation of the tumor microenvironment is responsible for tumorigenesis and metastasis in ccRCC. The role of long non-coding RNAs in the tumor immune of ccRCC remains unclear. The present study screened differentially expressed protein-coding genes and non-coding genes between ccRCC and normal tissues based on three datasets. The commonly deregulated genes were used to identify distant metastasis-related long non-coding RNAs (lncRNAs) and prognostic lncRNAs. Pearson correlation analysis was used to identify immune-related lncRNAs. A competing endogenous RNA network was constructed and hub lncRNAs were identified. A total of 1650 coding genes, 821 lncRNAs and 62 miRNAs were commonly deregulated in the three datasets. A total of 408 lncRNAs associated with the overall survival of patients with ccRCC were identified. Among them, 82 lncRNAs were distant metastasis-related. Further analysis identified 52 lncRNAs associated with the immune pathway. Functional analyses concordantly demonstrated the role of the 52 lncRNAs in metastasis and tumor immunology. The ceRNA network analysis indicated lncRNA DSCR9 as the key lncRNA regulator. Univariate and multivariate analysis in two independent cohorts validated that DSCR9 could be an independent risk factor for the progression-free survival of patients with ccRCC. Further analyses indicated that DSCR9 might be associated with the immunotherapeutic response. reverse transcription-quantitative PCR demonstrated that the RNA expression level of DSCR9 was upregulated in ccRCC compared with normal kidney samples. The present study demonstrated the potential of LncRNA DSCR9 in assessing the prognosis and developing future immunotherapy for patients with metastatic ccRCC.
远处转移是肾透明细胞癌(ccRCC)患者死亡的主要原因。肿瘤微环境失调是ccRCC肿瘤发生和转移的原因。长链非编码RNA在ccRCC肿瘤免疫中的作用尚不清楚。本研究基于三个数据集筛选了ccRCC与正常组织之间差异表达的蛋白质编码基因和非编码基因。利用这些共同失调的基因来鉴定远处转移相关的长链非编码RNA(lncRNA)和预后lncRNA。采用Pearson相关分析来鉴定免疫相关lncRNA。构建了竞争性内源性RNA网络并鉴定了枢纽lncRNA。在这三个数据集中,共有1650个编码基因、821个lncRNA和62个miRNA共同失调。共鉴定出408个与ccRCC患者总生存相关的lncRNA。其中,82个lncRNA与远处转移相关。进一步分析确定了52个与免疫途径相关的lncRNA。功能分析一致证明了这52个lncRNA在转移和肿瘤免疫学中的作用。ceRNA网络分析表明lncRNA DSCR9是关键的lncRNA调节因子。在两个独立队列中的单因素和多因素分析验证了DSCR9可能是ccRCC患者无进展生存的独立危险因素。进一步分析表明DSCR9可能与免疫治疗反应相关。逆转录定量PCR表明,与正常肾组织样本相比,DSCR9的RNA表达水平在ccRCC中上调。本研究证明了LncRNA DSCR9在评估转移性ccRCC患者预后和开发未来免疫治疗方面的潜力。
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