The Ion Channel-Related Gene Signatures Correlated With Diagnosis, Prognosis, and Individualized Treatment in Patients With Clear Cell Renal Cell Carcinoma.
The Ion Channel-Related Gene Signatures Correlated With Diagnosis, Prognosis, and Individualized Treatment in Patients With Clear Cell Renal Cell Carcinoma.
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DOI：
10.3389/fphar.2022.889142
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发表时间：
2022
影响因子：
5.6
通讯作者：
Zhou, Liqun
中科院分区：
文献类型：
--
作者：
Zhu, Zhenpeng;Lei, Zhenchuan;Qian, Jinqin;Zhang, Cuijian;Gong, Yanqing;Yin, Guicao;Li, Yifan;Li, Xuesong;Lin, Jian;Zhou, Liqun
背景：肾透明细胞癌(CcRCC)的早期发现和准确的预后评估对患者的预期寿命至关重要。离子通道相关基因(ICRGs)作为维持肾脏正常结构的组成部分，具有重要的诊断和预后价值。因此，我们利用多数据库系统地探讨了ICRGs在慢性肾细胞癌中的诊断、预后和治疗价值。方法：从包括癌症基因组图谱、ICGC、GEO和E-MTAB数据库在内的公共数据库中提取和整合ccRCC患者的RNA转录组谱和临床数据。离子通道相关基因来源于文献收集。使用套索和支持向量机-REF分析进行诊断特征。同时，使用套索分析进行预后信号分析。使用ConensusClusterPlus进行分子分型，并使用pRophetic软件包评估相应的治疗靶点。此外，根据COX回归分析的结果构建了预后诺模图。结果：我们成功地构建了5个ICRG的诊断特征和10个AUC值大于0.7的ICRG的预后特征，表现出良好的预测性能。根据中位风险评分，我们发现高危患者的预后明显更差。我们还根据预后ICRGs将ccRCC患者分为两组，两组之间的生存结果显著，对不同的临床治疗策略的敏感性不同。同时，我们构建了一个基于临床分子和标志物的诺模图，其预测效果优于标志物或目前的肿瘤-淋巴结-转移分期系统。结论：在本研究中，我们为肾细胞癌的早期发现、预后评估和个体化治疗建立了有用的标志。此外，KCNJ16值得在未来进行全面的探索。
Background: Early detection and precise prognostic evaluation of clear cell renal cell carcinoma (ccRCC) are crucial for patient life expectancy. Ion channel-related genes (ICRGs) are of great diagnostic and prognostic value as components that maintain the normal structure of the kidney. Therefore, we systematically explored the diagnostic, prognostic, and therapeutic value of ICRGs in ccRCC using the multi-database. Methods: RNA transcriptome profiles and clinical data of ccRCC patients were extracted and integrated from public databases including The Cancer Genome Atlas, ICGC, GEO, and E-MTAB databases. Ion channel-related genes were obtained from the literature collection. The diagnostic signature was performed using the LASSO and SVM-REF analyses. Meanwhile, the prognostic signature was conducted using the LASSO analyses. Molecular subtyping was performed using the ConsensusClusterPlus and the corresponding therapeutic targets were evaluated using the pRRophetic package. In addition, a prognostic nomogram was constructed based on the results of cox regression analyses. Results: We successfully constructed diagnostic signatures for five ICRGs and prognostic signatures for 10 ICRGs with AUC values greater than 0.7, showing good predictive performance. Based on the median risk score, we found that high-risk patients had a significantly worse prognosis. We also divided ccRCC patients into two clusters according to prognostic ICRGs, and there was a significant survival outcome between the two clusters and different sensitivity to diverse clinical therapeutic strategies. Meanwhile, we constructed a nomogram based on clinical molecules and signatures, and its predictive efficacy was better than the signature or the present tumor-node-metastasis staging system. Conclusion: In this study, we established useful signatures for early detection, prognosis evaluation, and individualized treatment for ccRCC. Moreover, KCNJ16 deserves to be explored comprehensively in the future.
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影响因子：
3.8
作者：
Khaitan D;Sankpal UT;Weksler B;Meister EA;Romero IA;Couraud PO;Ningaraj NS
通讯作者：
Ningaraj NS
影响因子：
3.8
作者：
Dong K;Chen W;Pan X;Wang H;Sun Y;Qian C;Chen W;Wang C;Yang F;Cui X
通讯作者：
Cui X
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影响因子：
3.8
作者：
Wang F;Chen Q;Huang G;Guo X;Li N;Li Y;Li B
通讯作者：
Li B
影响因子：
7.3
作者：
Gerlinger, Marco;Santos, Claudio R.;Spencer-Dene, Bradley;Martinez, Pierre;Endesfelder, David;Burrell, Rebecca A.;Vetter, Marcus;Jiang, Ming;Saunders, Rebecca E.;Kelly, Gavin;Dykema, Karl;Rioux-Leclercq, Nathalie;Stamp, Gordon;Patard, Jean Jacques;Larkin, James;Howell, Michael;Swanton, Charles
通讯作者：
Swanton, Charles
影响因子：
4
作者：
Li, Yan;Xu, Guoxiong;Chen, Gang
通讯作者：
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