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

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 5 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.

Apoptosis-Inducing Factor, Mitochondrion-Associated 3 (AIFM3) Protein Level in the Sera as a Prognostic Marker of Cholangiocarcinoma Patients

“…Apart from AIFM3, several mitochondrial proteins such as mitochondrial ribosomal protein, mitochondrial stress 70 protein (mortalin), pyruvate dehydrogenase kinase 3, and manganese superoxide dismutase have been detected in the serum, and has been used as serum marker for breast cancer, colorectal cancer, CCA, and ovarian cancer [ 20 , 21 , 22 , 23 ] The present results suggest that AIFM3 should be added as a mitochondrial protein marker in the sera of patients with CCA and probably other cancers. In the present study, serum AIFM3 level in the CCA patients group was significantly ( p < 0.0001) higher than that of HC.…”

Biomarkers of tumor invasiveness in proteomics (Review)

“…GRP75 (also known as Hsp70 or mortalin) plays a major role in the import and refolding of mitochondrial proteins, representing a potential serum biomarker of high prognostic value for patients with colorectal cancer (276). Additionally, Cruz et al demonstrated that this protein is a candidate biomarker of drug-resistant disease in ovarian cancer cell lines and tissues (277), while Niu et al described its involvement in modulating oncogenic Dbl-driven endocytosis (278).…”

Increased heat shock protein 70 (Hsp70) serum levels and low NK cell counts after radiotherapy – potential markers for predicting breast cancer recurrence?

“…The highly conserved member of the 70 kDa heat shock protein family Hsp70 is considered as a DAMP when released as a free molecule by dying cancer cells [11] whereas exosomal Hsp70 (exHsp70) which is actively released by viable tumor cells serves as a marker for viable tumor mass [12, 13]. Elevated exHsp70 serum levels as detected by the lipHsp70 ELISA [14] that detects both, free and exosomal Hsp70 have been found in breast cancer patients [15], patients with hepatocellular carcinoma, lung cancer [16], colorectal carcinoma [17, 18] and other cancer entities [19]. Although high exHsp70 levels are generally associated with an adverse prognosis also in breast cancer patients [20, 21], less is known about the role of free Hsp70 as a predictive marker for therapy response.…”