Abstract

Abstract Background: Although there have been some scientific advances in the diagnosis and treatment of hepatocellular carcinoma (HCC), there still remains challenges due to late presentation, therapeutic resistance, and recurrence. Because not all patients respond to therapeutic treatments, it is urgently needed to more precisely identify the patients who fail to achieve complete response and only have a partial response or no response to treatments. No biomarker(s) or assay(s) are currently available to predict the treatment response in HCC patients. Aim: To evaluate serological biomarkers in BCLC Stage B & C HCC patients undergoing treatment(s) including trans-arterial doxorubicin-eluting beads (DEB), trans-arterial radioembolization (Y-90 beads), and targeted molecular therapy (sorafenib). Methods: Fifty newly diagnosed primary HCC patients without any treatment were recruited between January 2014 and December 2018. Patients received, DEB, Y-90 beads, and Nexavar throughout their treatment course. The serum samples were collated before treatment (Pre-tx) and post treatment (Post-tx) at month 3, month 6 and month 9. A U-PLEX assay (Meso Scale Diagnostics) was performed to detect multiple serological biomarkers in serum, including growth factors (FGF19, HGF, insulin and FGF21) and inflammatory cytokines (IFN-γ, IL-17, IL-6, and TNF-α). The U-PLEX data were further validated by enzyme-linked immunosorbent assay. All patients were followed 3-5 years for survival with or without further surgical operations including tumor resection/ablation and orthotopic liver transplantation. Results: Based on the treatment outcome, patients were divided into 3 groups: a. overall survival (OS) < 1 year was defined as poor response; b. progression-free survival 3-5 years was defined as moderate response; and c. OS > 5 years was defined as good response. In the patients with moderate response and good response, the serum levels of FGF21 showed an increasing trend, with significant increases Post-tx at month 3, month 6 and month 9 (p < 0.05 vs Pre-tx). The serum levels of IFN-γ also showed an increasing trend, with significant increases at Post-tx-month 9 (p < 0.05 vs Pre-tx). In the patients with poor response, the serum levels of HGF and IL-6 were increased Post-tx, with statistically significance at Post-tx-month 6 (p < 0.05 vs Pre-tx). Increased serum levels of IL-17, TNF-α, FGF19, and insulin were found in the patients with poor response but no statistically significance reached (p > 0.05 versus Pre-tx). Conclusion: 1) Combination of growth factors and cytokines are applicable to find serological biomarkers in cancer patients for treatment response; 2) FGF21 and IFN-γ for good response and HGF and IL-6 for poor response may be used as biomarkers to monitor the HCC patients with adjuvant treatment(s); 3) Further study is needed to recruit more patients to correlate the serological biomarkers with their clinical outcome. Citation Format: Yan Li. Evaluation of multiple serological biomarkers for treatment response in HCC patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5140.

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