Clinicopathologic and Prognostic Association of GRP94 Expression in Colorectal Cancer with Synchronous and Metachronous Metastases

Int J Mol Sci. 2021 Jun 30;22(13):7042. doi: 10.3390/ijms22137042.

Abstract

Patients with advanced colorectal cancer (CRC) with distant metastases have a poor prognosis. We evaluated the clinicopathological relevance of GRP94 expression in these cases. The immunohistochemical expression of GRP94 was studied in 189 CRC patients with synchronous (SM; n = 123) and metachronous metastases (MM; n = 66), using tissue microarray; the association between GRP94 expression, outcome, and tumor-infiltrating lymphocytes (TILs) was also evaluated. GRP94 was expressed in 64.6% (122/189) patients with CRC; GRP94 positivity was found in 67.5% and 59.1% patients with SM and MM, respectively. In the SM group, high GRP94 expression was more common in patients with a higher density of CD4+ TILs (p = 0.002), unlike in the MM group. Survival analysis showed that patients with GRP94 positivity had significantly favorable survival (p = 0.030); after multivariate analysis, GRP94 only served as an independent prognostic factor (p = 0.034; hazard ratio, 0.581; 95% confidence interval, 0.351-0.961) in the SM group. GRP94 expression was detected in 49.4% of metastatic sites and showed significant heterogeneity between primary and metastatic lesions (p = 0.012). GRP94 is widely expressed in CRC with distant metastases; its expression was associated with favorable prognosis in the SM group, unlike in the MM group.

Keywords: GRP94; colorectal cancer; prognosis; tumor-infiltrating lymphocyte.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Membrane Glycoproteins / metabolism*
  • Middle Aged
  • Neoplasms, Multiple Primary / metabolism
  • Neoplasms, Multiple Primary / pathology*
  • Neoplasms, Second Primary / metabolism
  • Neoplasms, Second Primary / pathology*
  • Prognosis
  • Survival Analysis
  • Tissue Array Analysis
  • Up-Regulation*

Substances

  • Membrane Glycoproteins
  • endoplasmin