The prognostic significance of growth factors and circulating tumor cells in patients with hepatopancreatobiliary cancer

Hepatopancreatobiliary cancers have poor prognosis and the valuable prognostic markers are very limited in the management of the disease. In this study, the aim was to research the relationship of growth factors and circulating tumor cells (CTCs) with the prognosis of patients with hepatopancreatobiliary cancer The serum levels of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were measured by ELISA test. Density gradient centrifugation with the OncoQuick® assay was performed for isolation of CTCs from peripheral blood. Enriched samples underwent flow cytometric analysis. The cells characterized by CD45 negative and EpCAM positive signals were defined as CTCs. This study included 74 patiens with hepatopancreatobiliary cancer. The median levels of the VEGF and HGF were 22.26 ng/mL and 329.79 ng/mL, respectively. In patients with metastatic disease, the levels of HGF were significantly higher comparing to patients with operable disease (198.58 vs. 467.38, p=0.004). The median HGF level was 329.1 ng/mL in the subgroup of 62 patients with pancreatobiliary cancer. The median levels of monocyte, monocyte-to-lymphocyte ratio, C-reactive protein (CRP), and CRP-to-albumin ratio were significantly higher in the high HGF group compared to the low HGF group (p<0.050). The median CTCs count of 21 patients diagnosed with pancreatobiliary cancer, whose CTCs were isolated and identified, was 15. The rate of patients with negative surgical margin in the high CTC group was 23.1%, while the the rate of patients with positive surgical margin in the high CTC group was 83.3% (p=0.041). Median neutrophil/lymphocyte ratio (NLR) was found to be higher in the high CTC group compared to the low CTC group, which was close to statistical significance (2.37 vs. 1.41; p= 0.055). This study, which showed a significant relationship between the presence of metastasis and serum HGF level, reveals the importance of the HGF/c-MET signaling pathway in the development of metastasis and suggests that serum HGF level may be a prognostic biomarker in patients with hepatopancreatobiliary cancer. The relationship between serum HGF levels and systemic inflammation markers in patients with pancreatobiliary cancer was detected for the first time in the literature in this study. This relationship is thought to be the reflection of the relationship between HGF and inflammation in the tumor microenvironment to the peripheral blood. CTCs were identified to have a significant relationship with surgical margin positivity in this study for the first time, suggesting that the CTCs count in peripheral blood in preoperative patients may be a biomarker predicting positive surgical margin. This study which identified relationship close to statistical significance between CTCs and NLR, significantly contributes to the literature on the topic of the possible role of lymphocytes in CTC clearance.