Abstract

BackgroundPancreatic cancer is one of the most lethal tumors with poor prognosis, and lacks of effective biomarkers in diagnosis and treatment. The aim of this investigation was to identify hub genes in pancreatic cancer, which would serve as potential biomarkers for cancer diagnosis and therapy in the future.MethodsCombination of two expression profiles of GSE16515 and GSE22780 from Gene Expression Omnibus (GEO) database was served as training set. Differentially expressed genes (DEGs) with top 25% variance followed by protein-protein interaction (PPI) network were performed to find candidate genes. Then, hub genes were further screened by survival and cox analyses in The Cancer Genome Atlas (TCGA) database. Finally, hub genes were validated in GSE15471 dataset from GEO by supervised learning methods k-nearest neighbor (kNN) and random forest algorithms.ResultsAfter quality control and batch effect elimination of training set, 181 DEGs bearing top 25% variance were identified as candidate genes. Then, two hub genes, MMP7 and ITGA2, correlating with diagnosis and prognosis of pancreatic cancer were screened as hub genes according to above-mentioned bioinformatics methods. Finally, hub genes were demonstrated to successfully differ tumor samples from normal tissues with predictive accuracies reached to 93.59 and 81.31% by using kNN and random forest algorithms, respectively.ConclusionsAll the hub genes were associated with the regulation of tumor microenvironment, which implicated in tumor proliferation, progression, migration, and metastasis. Our results provide a novel prospect for diagnosis and treatment of pancreatic cancer, which may have a further application in clinical.

Highlights

  • Pancreatic cancer is one of the most lethal tumors with poor prognosis, and lacks of effective biomarkers in diagnosis and treatment

  • Numerous studies have focused on the investigation of biomarkers and molecular mechanisms of pancreatic cancers, and it is demonstrated that accumulated mutations in genes like oncogene Kras, and tumorsuppressor genes including P16 as well as TP53 resulted in the occurrence of pancreatic cancer [4]

  • All the 181 candidate genes were uploaded to STRING database, and proteinprotein interaction (PPI) network was Selection of hub genes by survival and cox analyses There were 178 pancreatic cancer samples and 4 normal samples in The Cancer Genome Atlas (TCGA) database

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Summary

Introduction

Pancreatic cancer is one of the most lethal tumors with poor prognosis, and lacks of effective biomarkers in diagnosis and treatment. The aim of this investigation was to identify hub genes in pancreatic cancer, which would serve as potential biomarkers for cancer diagnosis and therapy in the future. Molecular mechanisms researches demonstrated that overexpression of protein-coupled receptor GPR87 enhanced pancreatic cancer aggressiveness by activating NF-κB signaling pathway [7]. Another study demonstrated that suppressing microRNA-34 expression downregulated Bcl-2 and Notch1/2 in pancreatic cancer cells, as well as significantly inhibited cell growth and invasion, induced apoptosis and G1 and G2/M arrest in cell cycle, and sensitized the cells to chemotherapy and radiation [12]

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