TIMP1 mRNA in tumor-educated platelets is diagnostic biomarker for colorectal cancer

Aging (Albany NY). 2019 Oct 22;11(20):8998-9012. doi: 10.18632/aging.102366. Epub 2019 Oct 22.

Abstract

Platelets have been shown to promote the growth of tumors, including colorectal cancer. The RNA profile of tumor-educated platelets has the possibility for cancer diagnosis. We used RNA sequencing to identified the gene expression signature in platelets from colorectal cancer patients and healthy volunteers. We then verified the selected biomarkers from the RNA sequencing in a two-step case-control study using quantitative reverse-transcription polymerase chain reaction. We found that TIMP1 mRNA levels are higher in platelets from colorectal cancer patients than in platelets from healthy volunteers and patients with inflammatory bowel diseases. Additionally, TIMP1 mRNA expressed in platelets from colorectal cancer patients can be carried into colorectal cancer cells, where it promotes tumor growth in vivo and in vitro. These findings show that the TIMP1 mRNA in platelets is a potential independent diagnostic biomarker for colorectal cancer, and that platelets can carry RNAs into colorectal cancer cells to promote colorectal cancer development.

Keywords: RNA; TIMP1; biomarker; colorectal cancer; platelet.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • Apoptosis
  • Biomarkers, Tumor
  • Blood Platelets / metabolism*
  • Caco-2 Cells
  • Case-Control Studies
  • Cell Proliferation
  • Colitis, Ulcerative / metabolism
  • Colorectal Neoplasms / metabolism*
  • Crohn Disease / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • HT29 Cells
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Neoplasms, Experimental
  • RNA, Messenger / metabolism*
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism*

Substances

  • Biomarkers, Tumor
  • RNA, Messenger
  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1