Associations between the cyclooxygenase-2 expression in circulating tumor cells and the clinicopathological features of patients with colorectal cancer

J Cell Biochem. 2019 Apr;120(4):4935-4941. doi: 10.1002/jcb.27768. Epub 2018 Sep 27.

Abstract

While previous studies have shown that the number of circulating tumor cells (CTCs) alone is not sufficient to reflect tumor progression and that cyclooxygenase-2 (COX-2) expression is correlated with colorectal cancer (CRC) metastasis, COX-2 expression status and its potential functions in CTCs of CRC patients are unknown. Here, epithelial-mesenchymal transition (EMT) phenotype-based subsets of CTCs and the COX-2 expression status in CTCs were identified and their potential clinical values were assessed in 91 CRC patients. CTCs were enumerated in peripheral blood and subsets of CTCs (epithelial [eCTCs], mesenchymal [mCTCs], and biophenotypic [bCTCs]) and the COX-2 expression status were determined using the RNA in situ hybridization method. CTCs were detected in 80.2% (73 of 91) patients. Neither the total CTC nor eCTC numbers were found to significantly associate with any of the clinicopathological features. However, the number of mCTCs was significantly associated with distance metastasis (P = 0.035) and had a trend of being associated with lymph node metastasis ( P = 0.055). Among the 73 patients enrolled for evaluating COX-2 expression, 52.5% (38 of 73) were found to express COX-2 in CTCs, and COX-2 expression in CTCs was not found to associate with the clinicopathological factors. However, COX-2 expression in mCTCs tended to have a higher rate in patients with metastasis compared with those without metastasis (72.0% vs 42.8%; P = 0.072). Furthermore, COX-2 expression and mCTC marker expression correlated positively ( R = 0.287; P = 0.017). Further studies are required to investigate the clinical value of the expression of COX-2 in mCTCs, especially in CRC patients with the advanced tumor stage and distant metastasis.

Keywords: COX-2; circulating tumor cells; colorectal cancer; epithelial-mesenchymal transition.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Colorectal Neoplasms / enzymology*
  • Colorectal Neoplasms / pathology
  • Cyclooxygenase 2 / biosynthesis*
  • Female
  • Gene Expression Regulation, Enzymologic*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Proteins / biosynthesis*
  • Neoplastic Cells, Circulating / metabolism*
  • Neoplastic Cells, Circulating / pathology

Substances

  • Neoplasm Proteins
  • Cyclooxygenase 2
  • PTGS2 protein, human