Integrated expression profiles analysis reveals novel predictive biomarker in pancreatic ductal adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal human malignant tumor, with a dismal 5-year survival rate of less than 5%. The lack of specific symptoms at early tumor stages and the paucity of biomarkers contribute to the poor diagnosis of pancreatic ductal adenocarcinoma. To improve prognosis, a screening biomarker for early diagnosis of pancreatic cancer is in urgent need. We searched the databases of expression profiling by array on GEO, aiming at comparing gene expression profile of matched pairs of pancreatic tumor and adjacent non-tumor tissues, and we screen out 4 suitable series of gene expression microarray data (“GSE15471”, “GSE18670”, “GSE28735” and “GSE58561”). After carefully analyzing, 13 DEGs (MYOF, SLC6A6, S100P, HK2, IFI44L, OSBPL3, IGF2BP3, PDK4, IL1R2, ERO1A, EGLN3, PLAC8 and ACSL5) are significantly differentially expressed in four microarray databases in common. After analyzing mRNA expression data and clinical follow-up survey provided in the TCGA database and clinicopathological data of 137 pancreatic ductal adenocarcinoma patients, we carefully demonstrated that three of these differentially expressed genes (ERO1A, OSBPL3 and IFI44L) are correlated with poor prognosis of pancreatic ductal adenocarcinoma patients. In addition, we revealed that cell–matrix adhesion and extracellular matrix were top significantly regulated pathways in pancreatic ductal adenocarcinoma and depicted two protein-protein interactions networks of extracellular matrix related Genes which are dysregulated according to 4 gene expression microarray data mentioned above (“GSE15471”, “GSE18670”, “GSE28735” and “GSE58561”), hoping to shed light on the etiology of PDAC and mechanisms of drug resistance in PDAC in this study.

Recurrence‐associated gene signature optimizes recurrence‐free survival prediction of colorectal cancer

“…SEZ6L2 encoded a seizure-related protein, which was up-regulated in lung cancer and was considered to be a novel prognostic marker (Ishikawa et al, 2006). ERO1A has previously been reported to be induced by hypoxia in cervical cancer cell lines (Halle et al, 2012), and it was considered to be a predictive biomarker in pancreatic ductal adenocarcinoma (Li et al, 2017). RAB3B was a member of the RAS oncogene family, which has been demonstrated to be closely implicated in CRC (Cha et al, 2016;Hoogwater et al, 2010).…”

Curation of the Pancreatic Ductal Adenocarcinoma Subset of the Cancer Genome Atlas Is Essential for Accurate Conclusions about Survival-Related Molecular Mechanisms

“…3). Careful reexamination is especially needed when the results of integrative bioinformatic analysis predict novel biomarkers, such as OSBPL3 and IFI44L (13). After reanalysis using only 150 PDAC-TCGA samples, there was no statistically significant difference between low and high expressors of OSBPL3 or IFI44L with regards to survival; hence based on the PDAC-TCGA cohort these are not good predictive survival biomarkers (Fig.…”

Targeting glypican‐4 overcomes 5‐FU resistance and attenuates stem cell–like properties via suppression of Wnt/β‐catenin pathway in pancreatic cancer cells

“…A large number of genes have been revealed expressing aberrantly in pancreatic cancer. 33 These genes connect complex network and play important roles in chemoresistance and stem cell-like properties of pancreatic cancer. 34 Comprehensive bioinformatical analysis has provided novel research insights for studying the molecular mechanisms of a variety of diseases, including cancers.…”