Circulating mitochondrial stress 70 protein/mortalin and cytosolic Hsp70 in blood: Risk indicators in colorectal cancer

Int J Cancer. 2017 Dec 1;141(11):2329-2335. doi: 10.1002/ijc.30918. Epub 2017 Aug 21.

Abstract

Mitochondrial mortalin and cytosolic Hsp70 are essential chaperones overexpressed in cancer cells. Our goals were to reproduce our earlier findings of elevated circulating levels of mortalin and Hsp70 in colorectal cancer (CRC) patients with a larger patient cohort, to compare death risk assessment of mortalin, Hsp70, CEA and C19-9 and to assess their prognostic value in various CRC stages. Mortalin, Hsp70, CEA and CA19-9 levels were determined in sera of 235 CRC patients enrolled in the study and followed up 5 years after surgery. Association between their concentrations and patients' survival was analyzed by Kaplan-Meier estimator and subjected to Cox Proportional hazards analysis. Serum level of mortalin was independent of that of Hsp70, CEA and CA19-9, whereas Hsp70 level weakly correlated with CEA and CA19-9 levels. Improved short-term survival was found in early or advanced disease stages associated with lower mortalin and Hsp70 levels. Cox regression analysis showed a high mortality hazard (HR = 3.7, p < 0.001) in patients with both high mortalin and Hsp70 circulating levels. Multivariate analysis showed that high mortalin and Hsp70 significantly enhances risk score over a baseline model of age, number of affected lymph nodes, CEA, CA19-9, disease stage and perioperative therapy. Analysis of mortalin and Hsp70 in CRC patients' sera adds a high prognostic value to TNM stage and to CEA and CA19-9 and identifies patients with lower or higher survival probability in all CRC stages. Determination of mortalin and Hsp70 in blood could be a useful additive prognostic tool in guiding clinical management of patients.

Keywords: GRP75; Hsp70; colorectal cancer; mortalin; overall survival; risk factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Biomarkers, Tumor / blood*
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Cytosol
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • HSP70 Heat-Shock Proteins / blood*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Mitochondrial Proteins / blood*
  • Prognosis
  • Proportional Hazards Models
  • Risk

Substances

  • Biomarkers, Tumor
  • HSP70 Heat-Shock Proteins
  • HSPA9 protein, human
  • Mitochondrial Proteins