Li Hao, Chen Lu, Ke Zhi-Bin, Chen Shao-Hao, Xue Xue-Yi, Zheng Qing-Shui, Wei Yong, Zeng Kai, Xu Ning
Department of Anesthesiology, Anesthesiology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People's Republic of China.
Department of Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People's Republic of China.
Int J Gen Med. 2021 Oct 2;14:6325-6342. doi: 10.2147/IJGM.S332732. eCollection 2021.
This study aimed to develop and validate a novel angiogenesis-related gene (ARG) signature and molecular subtypes by bioinformatics analysis.
The transcriptome data and clinical data were obtained from TCGA and ICGC database. We performed consensus clustering analysis to identify angiogenesis molecular subtypes for ccRCC. Univariate and multivariate Cox regression analyses were used to develop a novel ARG-related signature as a prognostic biomarker for ccRCC. Internal and external validation were then performed in TCGA and ICGC cohort, respectively.
We identified a total of two angiogenesis molecular subtypes of ccRCC. The overall survival (OS) of subtype 1 ccRCC was significantly decreased compared with that of subtype 2 ccRCC (P=0.001). These two molecular subtypes have significantly different tumor microenvironment and immune checkpoint inhibitor sensitivities (P<0.05). Besides, we developed a novel signature based on three ARGs (including MSX1, TIMP1 and JAG2) for subtype 1 ccRCC. The difference in OS between high- and low-risk group was statistically significant in training cohort (P=0.009), test cohort (P=0.024), the whole type 1 cohort (P<0.001), and validation cohort (P=0.041). The AUC for one-year OS prediction was 0.732, 0.710, 0.725, and 0.645 in training cohort, test cohort, the whole type 1 cohort, and validation cohort, respectively. Independent prognostic analysis showed that this signature was an independent predictor for OS of subtype 1 ccRCC (P=0.028914). The power of this prognostic signature was superior to other signatures reported in previous studies.
We developed and successfully validated a novel ARG signature for predicting prognosis of subtype 1 ccRCC, which was superior to several previous signatures.
本研究旨在通过生物信息学分析开发并验证一种新型血管生成相关基因（ARG）特征及分子亚型。
转录组数据和临床数据来自TCGA和ICGC数据库。我们进行了一致性聚类分析以识别ccRCC的血管生成分子亚型。采用单因素和多因素Cox回归分析来开发一种新型的与ARG相关的特征，作为ccRCC的预后生物标志物。然后分别在TCGA和ICGC队列中进行内部和外部验证。
我们共识别出ccRCC的两种血管生成分子亚型。与2型ccRCC相比，1型ccRCC的总生存期（OS）显著降低（P = 0.001）。这两种分子亚型具有显著不同的肿瘤微环境和免疫检查点抑制剂敏感性（P < 0.05）。此外，我们为1型ccRCC开发了一种基于三个ARG（包括MSX1、TIMP1和JAG2）的新型特征。在训练队列（P = 0.009）、测试队列（P = 0.024）、整个1型队列（P < 0.001）和验证队列（P = 0.041）中，高风险组和低风险组之间的OS差异具有统计学意义。在训练队列、测试队列、整个1型队列和验证队列中，1年OS预测的AUC分别为0.732、0.710、0.725和0.645。独立预后分析表明，该特征是1型ccRCC患者OS的独立预测因子（P = 0.028914）。这种预后特征的预测能力优于先前研究中报道的其他特征。
我们开发并成功验证了一种用于预测1型ccRCC预后的新型ARG特征，其优于先前的几种特征。
