Large-scale transcriptome analysis identified RNA methylation regulators as novel prognostic signatures for lung adenocarcinoma
Lei Sun, Wenke Liu, Xiaowei Du, Xiang-Li Liu, Li Gao, Yao Yao, Tao Han, Wenya Li, Jia Gu
Abstract
Background: The abnormal expression of genes is an essential factor affecting the prognosis of cancer. RNA modification is a way of regulating post-transcriptional levels, including m6A, m5C, m1A RNA methylation. Studies have found that RNA methylation regulates tumorigenesis development and stem cell regeneration. However, there are few studies on lung adenocarcinoma. This study aims to explore the clinical value of RNA methylation for lung adenocarcinoma. Methods: We summarized thirty-one RNA methylation regulators. The training set was obtained from The Cancer Genome Atlas (TCGA) database, and the test set was obtained from the Gene Expression Omnibus (GEO) database. The Wilcoxon test was used to analyze the expression of RNA methylation regulators. We constructed tumor subgroup models and risk models based on the expression of those regulators. Principal component analysis (PCA) and the receiver operating characteristic (ROC) confirmed the accuracy of the models. Real-time polymerase chain reaction (PCR) validates the results in vitro. Results: Most RNA methylation regulators had distinct expressions in tumor tissues and adjacent tissues (P<0.05). All the models showed high predictive performance (AUC: 0.65–0.82), and the five-year survival of patients in each group was statistically different (P<0.05). The patients in the high-risk group were more likely to have a higher stage, more lymph node metastases, and distant metastases, showing a poor clinical outcome. Patients with high expression of NOP2 or HNRNP were more likely to have a poorly differentiated in vitro experiment. Conclusions: With our study, we found that the expressions of most RNA methylation regulators were significantly different in cancer and para-cancerous tissues. Different molecular phenotypes constructed by RNA methylation regulators can be independent risk factors for the prognosis of lung adenocarcinoma. Our study demonstrates the critical role of RNA methylation in lung adenocarcinoma, and it is expected to supply a reference for the prognostic stratification and treatment strategy development of lung adenocarcinoma.