Abstract Angiogenesis is a hallmark of cancer and is a critical process for the growth and survival of solid tumors. Hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) are pro-angiogenic factors overexpressed in solid cancers. Evidence from the literature supports the interplay between VEGF and the HGF/MET pathway. On the molecular level, upregulation of HGF increased VEGF expression and counteracted the effect of VEGF inhibitors in cancer cells. This study aimed to measure the circulating levels of HGF and VEGF in patients newly diagnosed with solid cancers and to assess the impact of their levels on the clinicopathologic tumor features and the clinical outcomes. Adult patients newly diagnosed with solid cancers (n=200) and their matched control subjects (n=200) were prospectively recruited from the Military Oncology Center and the Oncology Unit at King Abdullah University Hospital. The circulating levels of HGF and VEGF were measured using ELISA. Relevant demographic and clinical data were collected from the medical records, and tumor data were retrieved from pathology reports. The median circulating HGF levels were significantly higher in patients (median: 890.90 pg/ml; IQR: 576.01-1444.54) compared to their matched controls (median: 587.05; IQR: 436.74-968.09, p0.001). No significant differences were observed in VEGF serum levels between patients and controls. There was a significant positive correlation between the baseline circulating HGF and VEGF levels in patients with cancer (rho=0.291; p0.001). The circulating HGF levels correlated positively with the number of positive lymph nodes in patients (rho=0.288; p=0.027). Patients with gastric cancer had the highest median circulating HGF levels (median: 1367.75; IQR: 755.15-6407.07 pg/ml), while patients with breast cancer had the lowest circulating median levels of HGF (median: 738.78; IQR: 456.98-1071.76 pg/ml). No statistically significant difference was observed for the circulating levels of VEGF based on tumor type. The median VEGF serum concentration was significantly higher in patients with larger and more invasive tumors (median: 138.17; IQR: 72.12-260.28 pg/ml) compared to those with smaller tumor size (median: 101.78; IQR: 52.87-174.82 pg/ml, p=0.041). Patients who had death as their outcome had the highest baseline HGF serum levels compared to those with stable disease, regression, or progression (p=0.021). Alternatively, no significant difference in the median VEGF serum levels was found according to outcomes of first-line therapy. In conclusion, the baseline circulating levels of HGF may serve as a diagnostic biomarker in patients with solid cancer. Increased levels of serum HGF and VEGF were associated with adverse prognostic features and may define patients who could benefit from more aggressive therapy. Citation Format: Salam Sardiah, Nehad M. Ayoub, Mousa T. Atmeh, Mohammad S. Alkader, Qusai Y. Al-Share. The circulating levels of hgf and vegf in patients newly diagnosed with solid cancers: Prognostic significance and clinical relevance abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2304.
Sardiah et al. (Fri,) studied this question.