Discovery of Prognostic Signature Genes for Overall Survival Prediction in Gastric Cancer
COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE
Authors: Meng, Changyuan; Xia, Shusen; He, Yi; Tang, Xiaolong; Zhang, Guangjun; Zhou, Tong
Abstract
Background. Gastric cancer (GC) is one of the most common malignant tumors in the digestive system with high mortality globally. However, the biomarkers that accurately predict the prognosis are still lacking. Therefore, it is important to screen for novel prognostic markers and therapeutic targets.Methods. We conducted differential expression analysis and survival analysis to screen out the prognostic genes. A stepwise method was employed to select a subset of genes in the multivariable Cox model. Overrepresentation enrichment analysis (ORA) was used to search for the pathways associated with poor prognosis.Results. In this study, we designed a seven-gene-signature-based Cox model to stratify the GC samples into high-risk and low-risk groups. The survival analysis revealed that the high-risk and low-risk groups exhibited significantly different prognostic outcomes in both the training and validation datasets. Specifically, CGB5, IGFBP1, OLFML2B, RAI14, SERPINE1, IQSEC2, and MPND were selected by the multivariable Cox model. Functionally, PI3K-Akt signaling pathway and platelet-derived growth factor receptor (PDGFR) were found to be hyperactive in the high-risk group. The multivariable Cox regression analysis revealed that the risk stratification based on the seven-gene-signature-based Cox model was independent of other prognostic factors such as TNM stages, age, and gender.Conclusion. In conclusion, we aimed at developing a model to predict the prognosis of gastric cancer. The predictive model could not only effectively predict the risk of GC but also be beneficial to the development of therapeutic strategies.
CGB5 expression is independently associated with poor overall survival and recurrence-free survival in patients with advanced gastric cancer
CANCER MEDICINE
Authors: Yang, Yuxin; Shi, Yonghong; Hou, Yanjuan; Lu, Ying; Yang, Jinliang
Abstract
The human CGB5 gene encodes chorionic gonadotropin (hCG)beta 5, which is aberrantly expressed in trophoblastic neoplasm and in some non-trophoblastic neoplasms. Fucntional studies observed that it involved tumor initiation, growth, and metastatic outgrowth. In this study, using data from the International Cancer Genome Consortium (ICGC) and the Cancer Genome Atlas (TCGA)-stomach adenocarcinoma (STAD), we assessed the independent prognostic value of CGB5 expression in patients with primary gastric cancer (GC). Results showed that CGB5 expression was nearly not expressed in normal GC tissues. In comparison, its expression was detected in 214 of the 415 primary GC cases (51.6%) in TCGA-STAD and was associated with poor response to primary therapy and a higher risk of recurrence and death. In early stages, CGB5 expression was not a prognostic factor in terms of OS (HR: 1.448; 95% CI: 0.811-2.588, P = 0.211) or RFS (HR: 1.659; 95% CI: 0.778-3.540, P = 0.190). However, its expression was independently associated with unfavorable OS (HR: 1.719; 95% CI: 1.115-2.651, P = 0.014) and RFS (HR: 3.602; 95% CI: 1.708-7.598, P = 0.001) in advanced stages. Using deep sequencing data from TCGA-STAD, we found that CGB5 expression was not related to its genetic amplification or DNA methylation in GC. Based on these findings, we infer that CGB5 expression is common in GC patients and its expression might independently predict poor OS and RFS in advanced stages, but not in early stages of GC.