Noteworthy prognostic value of phospholipase C delta genes in early stage pancreatic ductal adenocarcinoma patients after pancreaticoduodenectomy and potential molecular mechanisms

Cancer Med. 2020 Feb;9(3):859-871. doi: 10.1002/cam4.2699. Epub 2019 Dec 6.

Abstract

The purpose of this investigation was to explore the prognostic value of phospholipase C delta (PLCD) genes in early stage pancreatic ductal adenocarcinoma (PDAC) and its potential molecular mechanisms. The prognostic value of PLCD genes in early stage PDAC was assessed using the Kaplan-Meier method and multivariate Cox proportional hazards regression model. Genome-wide correlation analysis was performed on PLCD3 to identify the highly correlated genes in the transcriptome. Then, PLCD3 and these correlated genes together underwent a bioinformatics analysis to elucidate the potential molecular biological functions of PLCD3 in PDAC. PLCD1 and PLCD3 are significantly overexpressed in PDAC. In PDAC patients, PLCD3 is overexpressed in certain groups of people with a history of alcoholism (P = .032). High expression of PLCD3 was found to be associated with lower overall survival (OS) of patients with early stage PDAC (P = .020; adjusted P = .016). A combination of PLCD3 and clinical variables was able to better predict the outcome of patients with early stage PDAC. These clinical variables are histological grade (P = .001; adjusted P = .001), targeted molecular therapy (P < .001; adjusted P < .001), radiation therapy (P = .002; adjusted P = .039), and residual resection (P = .001; adjusted P = .002). The bioinformatics analysis revealed that PLCD3 is associated with angiogenesis, intracellular signal transduction, and regulation of cell proliferation. In conclusion, PLCD3 may be a potential prognostic biomarker for early stage PDAC.

Keywords: clinical significance; early stage pancreatic ductal adenocarcinoma; molecular mechanism; pancreaticoduodenectomy; phospholipase C delta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Carcinoma, Pancreatic Ductal / diagnosis
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / therapy*
  • Cell Proliferation / genetics
  • Chemoradiotherapy, Adjuvant / methods
  • Computational Biology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Margins of Excision
  • Middle Aged
  • Molecular Targeted Therapy / methods
  • Neoplasm Staging
  • Pancreas / pathology
  • Pancreas / surgery
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / surgery*
  • Pancreaticoduodenectomy*
  • Phospholipase C delta / genetics*
  • Prognosis
  • RNA-Seq
  • Retrospective Studies
  • Signal Transduction / genetics

Substances

  • Biomarkers, Tumor
  • PLCD1 protein, human
  • PLCD3 protein, human
  • Phospholipase C delta