Orchestrating a biomarker panel with lncRNAs and mRNAs for predicting survival in pancreatic ductal adenocarcinoma

J Cell Biochem. 2018 Sep;119(9):7696-7706. doi: 10.1002/jcb.27119. Epub 2018 Jun 20.

Abstract

The low survival of patients with pancreatic ductal adenocarcinoma (PDAC) makes the treatment of this disease one of the most challenging task in modern medicine. Here, by mining a large-scale cancer genome atlas data set of pancreatic cancer tissues, we identified 21 long noncoding RNAs (lncRNAs) that significantly associated with overall survival in patients with PDAC (P < .01). Further analysis revealed that 8 lncRNAs turned out to be independently correlated with patients' overall survival, and the risk score could be calculated based on their expression. To obtain a better predicting power, we integrated lncRNA data with a total of 410 differently expressed messenger RNAs (mRNAs) screened from PDAC and normal tissues in gene expression omnibus (GEO) database. The integration resulted in a much better panel including 8 lncRNAs (RP3.470B24.5, CTA.941F9.9, RP11.557H15.3, LINC00960, AP000479.1, LINC00635, LINC00636, and AC073133.1) and 8 mRNAs (DHRS9, ONECUT1, OR8D4, MT1M, TCN1, MMP9, DPYSL3, and TTN) to predict prognosis. A functional evaluation showed that these lncRNAs might play roles in pancreatic secretion, cell adhesion, and proteolysis. Using normal and pancreatic cancer cell lines, we confirmed that a majority of identified lncRNAs and mRNAs showed altered expressions in pancreatic cancer cells. Especially, LINC01589, LINC00960, TCN1, and MT1M showed a profoundly increased expression in pancreatic cancer cells, which suggests their potentially important role in pancreatic cancer. The results of our work indicate that lncRNAs have vital roles in PADC and provide new insights to integrate multiple kinds of markers in clinical practices.

Keywords: long noncoding RNAs (lncRNAs); messenger RNAs (mRNAs); pancreatic ductal adenocarcinoma (PDAC); survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Carcinoma, Pancreatic Ductal / genetics*
  • Data Mining
  • Female
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Metallothionein / genetics
  • Oligonucleotide Array Sequence Analysis
  • Pancreatic Neoplasms / genetics*
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • RNA, Messenger / genetics*
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • MT1M protein, human
  • RNA, Long Noncoding
  • RNA, Messenger
  • Metallothionein