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Article type: Research Article
Authors: Gráf, Lászlóa | Barabás, Lórándb | Madaras, Balázsc | Garam, Nóraa | Maláti, Évad | Horváth, Lauraa | Prohászka, Zoltána | Horváth, Zsolte | Kocsis, Judita; e; *
Affiliations: [a] 3rd Department of Internal Medicine, Semmelweis University, Budapest 1125, Hungary | [b] 2nd Department of Surgery, Semmelweis University, Budapest 1125, Hungary | [c] National Institute of Oncology, Budapest 1122, Hungary | [d] János Balassa Hospital, County Hospital Tolna, Szekszárd 7100, Hungary | [e] Department of Oncoradiology, Bács-Kiskun County Hospital, Kecskemét H6000, Hungary
Correspondence: [*] Corresponding author: Judit Kocsis, 3rd Department of Internal Medicine, Semmelweis University, Kútvölgyi út 4, Budapest 1125, Hungary. E-mail: [email protected].
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.
Keywords: Hsp70, colorectal cancer, prognostic model, CRP, survival
DOI: 10.3233/CBM-181683
Journal: Cancer Biomarkers, vol. 23, no. 4, pp. 539-547, 2018
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