Early predictive value of circulating biomarkers for sorafenib in advanced hepatocellular carcinoma

ABSTRACT

Introduction

Sorafenib is currently the first-line therapeutic regimen for patients with advanced hepatocellular carcinoma (HCC). However, many patients did not experience any benefit and suffered extreme adverse events and heavy economic burden. Thus, the early identification of patients who are most likely to benefit from sorafenib is needed.

Areas covered

This review focused on the clinical application of circulating biomarkers (including conventional biomarkers, immune biomarkers, genetic biomarkers, and some novel biomarkers) in advanced HCC patients treated with sorafenib. An online search on PubMed, Web of Science, Embase, and Cochrane Library was conducted from the inception to 15 August 2021. Studies investigating the predictive or prognostic value of these biomarkers were included.

Expert opinion

The distinction of patients who may benefit from sorafenib treatment is of utmost importance. The predictive roles of circulating biomarkers could solve this problem. Many biomarkers can be obtained by liquid biopsy, which is a less or noninvasive approach. The short half-life of sorafenib could reflect the dynamic changes of tumor progression and monitor the treatment response. Circulating biomarkers obtained from liquid biopsy resulted as a promising assessment method in HCC, allowing for better treatment decisions in the near future.

Abbreviations

Alpha-fetoprotein (AFP); American Association for the Study of Liver Diseases (AASLD); Angiopoietin (Ang); Barcelona Clinic Liver Cancer stage (BCLC); Circulating endothelial progenitor (CEP); Circulating free DNA (cfDNA); Complete response (CR); Des-γ-carboxy prothrombin (DCP); Endothelium-derived nitric oxide synthase (eNOS); Hepatocellular carcinoma (HCC); Hepatocyte growth factor (HGF); Hepatoma arterial-embolization prognosis score (HAP); High mobility group box 1 (HMgb1); Interferon-gamma (IFN-γ); Long non-coding RNA (lncRNAs); Micro RNAs (miRNAs); Monocyte-to-lymphocyte ratio (MLR); National Comprehensive Cancer Network (NCCN); Neutrophil-lymphocyte ratio (NLR); Newcastle-Ottawa Scale (NOS); Nitric oxide (NO); Overall survival (OS); Partial response (PR); Platelet-lymphocyte ratio (PLR); Prediction of survival in advanced sorafenib-treated HCC (PROSASH); Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA); Prognostic nutritional index (PNI); Progression-free survival (PFS); Progressive disease (PD); Randomized controlled trials (RCTs); Response Evaluation Criteria in Solid Tumors (RECIST); Single nucleotide polymorphisms (SNPs); Sorafenib advanced HCC prognosis score (SAP); Stable disease (SD); Time to progression (TTP); Transcatheter arterial chemoembolization (TACE); Vascular endothelial growth factor (VEGF).

KEYWORDS:

• Hepatocellular carcinoma
• sorafenib
• circulating biomarker
• survival benefit
• liquid biopsy

Acknowledgments

Dr. Xiangyong Hao thanks the financial support from the Natural Science Foundation for Young Scientists and the Science & Technology Planning Project of Gansu Province (18JR3RA058), the Gansu Province Youth Innovative Talents Project (2021-02, Xiangyong Hao), Health Industry Scientific Research Program of Gansu Province (GSWSKY2020-06), and Research Projects of Gansu Provincial Hospital (Grant No.: 19SYPYB-7, 18GSSY3-1).

Article highlights

1. Sorafenib is not suitable for all advanced HCC patients, which causes some patients to suffer adverse drug reactions without having any beneficial effect from sorafenib treatment.

2. Several circulating biomarkers, including AFP, VEGF, Ang-2, DCP, IL and systemic inflammatory ratios, show a promising potential as predictors of the response to sorafenib in advanced HCC.

3. Genetic circulating biomarkers can also predict the response to sorafenib, but the exact mechanism and the functional analysis of these biomarkers remain to be clarified.

4. Circulating biomarkers have many advantages compared with imaging assessment and clinical predictors, but many obstacles need to be overcome.

5. The combined evaluation of circulating biomarkers, mRECIST criteria, clinical predictors, and sorafenib-related adverse events may provide a better prediction of sorafenib efficacy.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author Contributions

Tiankang Guo and Xiangyong Hao were involved in the conception and design; Shaoming Song, Mingzhen Bai, Xiaofei Li, Shiyi Gong, Wenwen Yang, Caining Lei, Hongwei Tian, and Moubo Si were involved in the analysis and interpretation of data; Shaoming Song, Mingzhen Bai, and Xiaofei Li were involved in the drafting of the paper or revising; Tiankang Guo and Xiangyong Hao were involved the final approval of the version to be published; and that all authors agree to be accountable for all aspects of the work.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This research was funded by the Natural Science Foundation for Young Scientists and the Science & Technology Planning Project of Gansu Province (18JR3RA058), the Gansu Province Youth Innovative Talents Project (2021-02, Xiangyong Hao), Health Industry Scientific Research Program of Gansu Province (GSWSKY2020-06), and Research Projects of Gansu Provincial Hospital (Grant No.: 19SYPYB-7, 18GSSY3-1).