Department of Clinical Medicine, The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu, China.
Department of General Surgery, Gansu Provincial Hospital, Lanzhou, Gansu, China.
Expert Rev Mol Diagn. 2022 Mar;22(3):361-378. doi: 10.1080/14737159.2022.2049248. Epub 2022 Mar 11.
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.
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.
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.
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).
索拉非尼目前是治疗晚期肝细胞癌（HCC）患者的一线治疗方案。然而，许多患者并未从中获益，反而遭受了极端的不良反应和沉重的经济负担。因此，需要早期识别最有可能从索拉非尼治疗中获益的患者。
本综述重点介绍了循环生物标志物（包括常规生物标志物、免疫生物标志物、遗传生物标志物和一些新型生物标志物）在接受索拉非尼治疗的晚期 HCC 患者中的临床应用。对 PubMed、Web of Science、Embase 和 Cochrane Library 进行了在线检索，检索时间从创建到 2021 年 8 月 15 日。纳入了研究这些生物标志物预测或预后价值的研究。
区分可能从索拉非尼治疗中获益的患者至关重要。循环生物标志物的预测作用可以解决这个问题。许多生物标志物可以通过液体活检获得，这是一种微创或非侵入性的方法。索拉非尼的半衰期较短，可反映肿瘤进展的动态变化，并监测治疗反应。从液体活检中获得的循环生物标志物是 HCC 有前途的评估方法，有望在不久的将来做出更好的治疗决策。
甲胎蛋白（AFP）；美国肝病研究协会（AASLD）；血管生成素（Ang）；巴塞罗那临床肝癌分期（BCLC）；循环内皮祖细胞（CEP）；循环游离 DNA（cfDNA）；完全缓解（CR）；去γ-羧基凝血酶原（DCP）；内皮一氧化氮合酶（eNOS）；肝细胞癌（HCC）；肝细胞生长因子（HGF）；肝癌动脉栓塞预后评分（HAP）；高迁移率族蛋白 1（HMgb1）；γ-干扰素（IFN-γ）；长链非编码 RNA（lncRNAs）；微小 RNA（miRNAs）；单核细胞-淋巴细胞比值（MLR）；国家综合癌症网络（NCCN）；中性粒细胞-淋巴细胞比值（NLR）；纽卡斯尔-渥太华量表（NOS）；一氧化氮（NO）；总生存期（OS）；部分缓解（PR）；血小板-淋巴细胞比值（PLR）；预测索拉非尼治疗晚期 HCC 的生存（PROSASH）；系统评价和荟萃分析的首选报告项目（PRISMA）；预后营养指数（PNI）；无进展生存期（PFS）；进展性疾病（PD）；随机对照试验（RCTs）；实体瘤反应评估标准（RECIST）；单核苷酸多态性（SNPs）；索拉非尼晚期 HCC 预后评分（SAP）；稳定疾病（SD）；进展时间（TTP）；经导管动脉化疗栓塞（TACE）；血管内皮生长因子（VEGF）。
