Prognostic significance of hepatocyte growth factor in non-metastatic colorectal cancer

Abstract

Hepatocyte growth factor (HGF), produced by mesenchymal cells, stimulates mitogenesis and angiogenesis in tumor cells. Tumor cells of some solid tumors do not secrete HGF. The aim of the study was to evaluate the prognostic significance of HGF expression in tumor tissue in colorectal cancer (CRC). The study included 50 patients with stage II-III colorectal cancer; they underwent radical surgical treatment, followed by adjuvant chemotherapy according to the FOLFOX/XELOX regimen. In primary tumor samples, quantitative PCR was used to assess the level of HGF expression. Statistical processing of the obtained data was carried out using STATISTICA 13.0, BioStat v.7.1., and Jamovi 1.6.8 software. The study aims to study a new marker. Comparison of characteristics in the case of non-normal distribution was carried out using the nonparametric Mann–Whitney U test. Cox and Kaplan–Meier linear regression tests were used to analyze progression-free survival. When discussing the results, we used our previously obtained data on the level of expression of TGF-β and CXCL8 in the tumor tissue. As a result of the studies, it was found that in 60% of tumor samples HGF was not expressed, but it was significantly higher than in the resection line samples. Analysis of relapse-free survival in patients with CRC according to the level of HGF expression (predicted level by proportional hazards assessment – 0.7) showed that the median survival in groups 1 (HGF expression more than 0.7) and 2 (HGF expression less than 0.7) was 23.3 and 62.9 months, respectively (long rank test p = 0.215). It was shown that the level of HGF mRNA in CRC tumors does not depend on age, stage of the disease, and sensitivity to FOLFOX/XELOX chemotherapy. The expression level is significantly reduced in tumors with a KRAS mutation and increased in those with a BRAF mutation, in poorly differentiated tumors. Using the level of HGF expression in the tumor tissue of patients with non-metastatic CRC before the start of chemotherapy to assess the prognosis of the relapse-free period is only possible in conjunction with the expression of TGF-β, CXCL8 in the tissue and the level of CEA in the blood of these patients.