State Key Laboratory of Natural Medicines, Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Nanjing, P.R. China.
Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, P.R. China.
Cell Prolif. 2020 Aug;53(8):e12861. doi: 10.1111/cpr.12861. Epub 2020 Jun 28.
Due to the limited evaluation of the prognostic value of RNA processing genes (RPGs), which are regulators of alternative splicing events (ASEs) that have been shown to be associated with tumour progression, this study sought to determine whether colorectal cancer (CRC) could be further stratified based on the expression pattern of RPGs.
The gene expression profiles of CRCs were collected from TCGA (training set) and three external validation cohorts, representing 1060 cases totally. Cox regression with least absolute shrinkage and selection operator (LASSO) penalty was used to develop an RNA processing gene index (RPGI) risk score. Kaplan-Meier curves, multivariate Cox regression and restricted mean survival (RMS) analyses were harnessed to evaluate the prognostic value of the RPGI.
A 22-gene RPGI signature was developed, and its risk score served as a strong independent prognostic factor across all data sets when adjusted for major clinical variables. Moreover, ASEs for certain genes, such as FGFR1 and the RAS oncogene family, were significantly correlated with RPGI. Expression levels of genes involved in splicing- and tumour-associated pathways were significantly correlated with RPGI score. Furthermore, a combination of RPGI with age and tumour stage resulted in significantly improved prognostic accuracy.
Our findings highlighted the prognostic value of RPGs for risk stratification of CRC patients and provide insights into specific ASEs associated with the development of CRC.
由于 RNA 处理基因（RPGs）的预后价值评估有限，这些基因是可变剪接事件（ASEs）的调节剂，已被证明与肿瘤进展有关，因此本研究旨在确定是否可以根据 RPGs 的表达模式进一步对结直肠癌（CRC）进行分层。
从 TCGA（训练集）和三个外部验证队列中收集了 CRC 的基因表达谱，总共代表了 1060 例病例。采用 Cox 回归与最小绝对值收缩和选择算子（LASSO）惩罚相结合的方法，开发了 RNA 处理基因指数（RPGI）风险评分。利用 Kaplan-Meier 曲线、多变量 Cox 回归和限制平均生存（RMS）分析评估 RPGI 的预后价值。
开发了一个 22 个基因的 RPGI 特征，并且在调整了主要临床变量后，其风险评分在所有数据集中都是一个强有力的独立预后因素。此外，某些基因的 ASEs，如 FGFR1 和 RAS 癌基因家族，与 RPGI 显著相关。参与剪接和肿瘤相关途径的基因的表达水平与 RPGI 评分显著相关。此外，将 RPGI 与年龄和肿瘤分期相结合，可以显著提高预后准确性。
我们的研究结果突出了 RPGs 对 CRC 患者风险分层的预后价值，并提供了与 CRC 发展相关的特定 ASEs 的见解。
