Development of a Gene Risk Signature for Patients of Pancreatic Cancer

Abstract

Background. Pancreatic cancer is a highly malignant solid tumor with a high lethality rate, but there is a lack of clinical biomarkers that can assess patient prognosis to optimize treatment. Methods. Gene-expression datasets of pancreatic cancer tissues and normal pancreatic tissues were obtained from the GEO database, and differentially expressed genes analysis and WGCNA analysis were performed after merging and normalizing the datasets. Univariate Cox regression analysis and Lasso Cox regression analysis were used to screen the prognosis-related genes in the modules with the strongest association with pancreatic cancer and construct risk signatures. The performance of the risk signature was subsequently validated by Kaplan–Meier curves, receiver operating characteristic (ROC), and univariate and multivariate Cox analyses. Result. A three-gene risk signature containing CDKN2A, BRCA1, and UBL3 was established. Based on KM curves, ROC curves, and univariate and multivariate Cox regression analyses in the TRAIN cohort and TEST cohort, it was suggested that the three-gene risk signature had better performance in predicting overall survival. Conclusion. This study identifies a three-gene risk signature, constructs a nomogram that can be used to predict pancreatic cancer prognosis, and identifies pathways that may be associated with pancreatic cancer prognosis.

Effects of metformin on cancers in experimental and clinical studies: Focusing on autophagy and AMPK/mTOR Signaling Pathways

“…The prevalence and fatality rates of pancreatic cancer, a solid aggressive tumour, are both rising [97]. As demonstrated by Chen et al, co-treatment of the human pancreatic cancer cell lines ASPC-1 and PANC-1 with MET (30 mM) and pitavastatin (10 mM) could more effectively decrease cell proliferation and migration, support cell cycle arrest, stimulate AMPK, and suppress PI3K/mTOR while trigger cell apoptosis and autophagy.…”

Effects of metformin on cancers in experimental and clinical studies: Focusing on autophagy and AMPK/mTOR signaling pathways

“…The prevalence and fatality rates of pancreatic cancer, a solid aggressive tumour, are both rising. 106 Therefore, a dual part was performed by MET in controlling MIN6 pancreatic β cell survival. 107…”

“…The prevalence and fatality rates of pancreatic cancer, a solid aggressive tumour, are both rising 106 . As demonstrated by Chen et al, co‐treatment of the human pancreatic cancer cell lines ASPC‐1 and PANC‐1 with MET (30 mM) and pitavastatin (10 mM) could more effectively decrease cell proliferation and migration, support cell cycle arrest, stimulate AMPK, and suppress PI3K/mTOR while trigger cell apoptosis and autophagy.…”

A New Potential Therapeutic Target for Cancer in Ubiquitin-Like Proteins—UBL3

“…Pancreatic cancer (PC) is one of the most malignant tumors with a very poor prognosis and it has the lowest five-year survival rate of all tumors in the United States at 11% [ 116 ]. Liu et al constructed a three-gene risk profile containing UBL3, CDKN2A, and BRCA1for predicting overall survival in pancreatic cancer patients [ 117 ]. The study used multivariate cox regression analysis to show that three-gene characteristics could be an independent predictor of prognosis in pancreatic cancer patients.…”

“…The study used multivariate cox regression analysis to show that three-gene characteristics could be an independent predictor of prognosis in pancreatic cancer patients. Among them, UBL3 expression was significantly downregulated in the high-risk group and negatively correlated with risk score [ 117 ]. EphA2 and MMP14, which are UBL3-interacting sEV proteins, are known to be key molecules for PC drug responses.…”