High serum Hsp70 level predicts poor survival in colorectal cancer: Results obtained in an independent validation cohort

Abstract

BACKGROUND: Hsp70 plays important role in the development and progression of cancer. Previously we described the association between serum Hsp70 levels and mortality of colorectal cancer. OBJECTIVE: In this new prospective study we aimed to confirm and extend our previous findings in a larger cohort of patients, based on a longer follow-up period. METHODS: Two hundred and thirty-two patients diagnosed with colorectal cancer were enrolled in the study. Baseline serum Hsp70 level and classical biomarker levels were measured. Patients were treated according to stage of the tumor and follow-up lasted for a median 46.4 months. RESULTS: We found that serum Hsp70 concentrations increase significantly with stage of the disease (1.79; 2.23 and 3.21 ng/ml in stage I+II, III and IV respectively, p = 0.012 and 0.002, Mann-Whitney test) and with other known biomarkers of the disease. We managed to confirm our previous findings that high baseline serum Hsp70 level (> 1.64 ng/ml) predicted poor 5-year survival (risk of death HR: 1.94 CI: 1.294-2.909; univariate; HR: 2.418 CI: 1.373-4.258; multivariate Cox regression analysis) in the whole patient population and also in subgroups of stage IV and stage III disease. The strongest association was observed in women under age of 70 (HR: 8.12, CI: 2.02-35.84; p = 0.004; multivariate Cox regression). The power of this colorectal cancer prognostic model could be amplified by combining Hsp70 levels and inflammatory markers. Patients with high Hsp70, CRP and high baseline WBC or platelet count had 5-times higher risk of death (HR: 5.07 CI: 2.74-9.39, p < 0.0001; and HR: 4.98 CI: 3.08-8.06, p < 0.0001 respectively). CONCLUSIONS: These results confirm and validate our previous findings that serum Hsp70 is a useful biomarker of colorectal cancer.

Monitoring HSP70 exosomes in cancer patients’ follow up: a clinical prospective pilot study

“…High expression of HSPs, particularly HSP70 and HSP90, has been shown to correlate with clinical parameters such as diagnosis, prognosis and/or response to therapy in a wide variety of cancers, both at the intracellular [15,[19][20][21][22][23][24][25] and extracellular levels [2,11,16,24,[26][27][28][29][30]. Our findings here provide for the first time in a prospective cohort an overview of HSP70 expression (circulating, both in exosomes and soluble, and within the tumour) and indicate that exosomal HSP70 hold promises as a potential predictor of tumour growth/ spread for the monitoring of cancer patients bearing HSP70-expressing tumours.…”

Heat Shock Proteins: Agents of Cancer Development and Therapeutic Targets in Anti-Cancer Therapy

“…In cancer cells, HSP70 functions to induce mitotic signals and suppress apoptosis as well as oncogene induced senescence [46]. The increased expression of HSP70 has been indicated as a poor prognostic marker for a variety of cancers, including breast, lung, ovarian, colorectal, and pancreatic cancers and glioblastoma [45,[47][48][49][50]. Among HSP70 family, five members have been especially well examined in association with cancer, which are stress-inducible HSP70s, HSP72 (HSPA1) and HSP70B (HSPA6), and constitutively expressed HSP70s, HSC70 (HSPA8), GRP75/Mortalin (HSPA9), and GRP78 (HSPA5) [51,52].…”

The Prognostic Significance of Hsp70 in Patients with Colorectal Cancer Patients: A PRISMA-Compliant Meta-Analysis

“…Another 42 records had insufficient data for HR calculation. Finally, 11 articles with 2269 patients were used [21][22][23][25][26][27][28][29][30][31][32]. The 11 articles had a sample size of 167 to 256 (average 206) (Table 1).…”

“…Studies have shown that Hsp70 expression is upregulated in various carcinoma tissues and could be a potential biomarker [7]. Besides, previous studies have reported that Hsp70 overexpression is associated with poor survival in some cancers, including breast carcinoma [8][9][10], esophageal adenocarcinoma [11], non-small-cell lung cancer [12], prostate cancer [13,14], gastric cancer [15,16], leukemia [17], hepatocellular carcinoma [18,19], pancreatic cancer [20], and colon cancer [21][22][23]. However, no study has reported the relationship between the Hsp70 expression level and prognosis of colorectal cancer patients.…”