Identification of hub genes with diagnostic values in pancreatic cancer by bioinformatics analyses and supervised learning methods

World J Surg Oncol. 2018 Nov 14;16(1):223. doi: 10.1186/s12957-018-1519-y.

Abstract

Background: 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.

Methods: Combination 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.

Results: After 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.

Conclusions: All 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.

Keywords: Bioinformatics analysis; Diagnosis; Differentially expressed genes; Hub genes; Pancreatic cancer.

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Computational Biology
  • Datasets as Topic
  • Disease Progression
  • Gene Expression Profiling
  • Humans
  • Pancreas / pathology
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Prognosis
  • Protein Interaction Maps / genetics*
  • Supervised Machine Learning
  • Survival Analysis
  • Tissue Array Analysis
  • Tumor Microenvironment / genetics*

Substances

  • Biomarkers, Tumor