Colorectal cancer (CRC) is the second leading tumor diagnosis in women and men in the Czech Republic. Patient outcome depends on tumor stage at the time of diagnosis and, in metastatic disease, on the localization and extent of distant metastases. The early detection of metastatic liver disease is an important indication for liver surgery. Therefore, novel biomarkers are urgently required. Serum samples were collected from 97 patients with histologically confirmed metastatic CRC at the time of diagnosis or at the time of progression during palliative treatment, and 79 samples from healthy controls. All patients exhibited adequate liver and renal function and signed informed consent was obtained from all patients included in the current study. The serum levels of Heat shock protein 60 (HSP60), Chitinase-3-like protein 1 (CHI3L1) and Insulin-like growth factor binding protein 2 (IGFBP-2) were measured using immunochemistry. The serum levels of HSP60, CHI3L1 and IGFBP-2 were significantly higher in patients with CRC compared with healthy controls. When compared with carcinoembryonic antigen (CEA), HSP60 exhibited the same sensitivity and specificity, while CHI3L1 and IGFBP-2 exhibited decreased sensitivity. Additionally, the serum levels of HSP60 and IGFBP-2 were indicated to be correlated with the presence of liver metastases, which is in contrast to CEA and Cancer antigen 19-9 (CA19-9). Patients with higher HSP60 and IGFBP-2 levels exhibited a significantly worse survival (P<0.001 and 0.007, respectively). The results of the current study indicate HSP60 to be an effective biomarker in patients with metastatic CRC, with it exhibiting an equal sensitivity to CEA. Additionally, HSP60 and IGFBP-2 levels also strongly correlated with extension of liver metastases and exhibited a prognostic value that contrasted that of CEA.

1st Department of Surgery Department of Abdominal Thoracic Surgery and Traumatology 1st Faculty of Medicine Charles University and General University Hospital Prague 128 08 Prague 2 Czech Republic

4th Department of Internal Medicine Department of Gastroenterology and Hepatology 1st Faculty of Medicine Charles University and General University Hospital Prague 128 08 Prague 2 Czech Republic

Department of Oncology 1st Faculty of Medicine Charles University and General University Hospital Prague 128 08 Prague 2 Czech Republic

Department of Urology 1st Faculty of Medicine Charles University and General University Hospital Prague 128 08 Prague 2 Czech Republic

Institute of Medical Biochemistry and Laboratory Diagnostics 1st Faculty of Medicine Charles University and General University Hospital Prague 128 08 Prague 2 Czech Republic

Surgery Department 2nd Faculty of Medicine Charles University and Military University Hospital Prague 169 02 Prague 6 Czech Republic

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