Novel circulating biomarker digital scores for assessing treatment response in liver cancer

项目摘要/摘要 肝细胞癌是世界范围内癌症相关死亡的主要原因之一。本地 消融和肝动脉化疗栓塞术(TACE)是肝细胞癌最常用的治疗方法。 治疗后，患者接受放射成像以评估治疗反应。正在评估 由于治疗相关的非特异性改变，局部消融或TACE的治疗反应往往具有挑战性 明确的评估通常需要重复的横断面成像。同样，还有穷人 治疗后肿瘤存活率的放射学-组织学相关性：38%的肝细胞癌患者的结果不一致 局部消融或TACE后的患者。而血清甲胎蛋白(AFP)可以帮助评估治疗 治疗前，不到一半的肝细胞癌患者甲胎蛋白升高。这限制了它的用途 以便更广泛地实施。此R21提案的主要目标是调查小说的性能 评价肝细胞癌治疗反应的循环生物标记物数字评分。 最近，朱博士(Pi)和Tseng博士(共同研究员)开发了一种流线型肝癌细胞外 囊泡(EV)数字评分检测结合了两项强大的技术，即EV点击芯片用于纯化 肝细胞癌EVS和逆转录液滴数字聚合酶链式反应(RT-ddPCR)定量检测肝细胞癌特异性基因 在早期肝癌检测中表现突出的标志物。此外，杨博士(联系人-派) 由三种肝细胞癌蛋白肿瘤标志物(AFP-L3、AFP和DES)得出的Galad评分。 凝血酶原)对早期肝细胞癌的诊断具有很高的准确性。这两个分数都反映了肿瘤的负担 我们的试验数据显示，它们在评估治疗反应方面表现良好。因此，中央 R21方案的假设是治疗前后的肝细胞癌EV数字评分、Galad评分和 两个独立评分的整合(即，肝癌EV-Galad数字评分)可以评估肝癌的治疗 回应。杨博士和朱博士将进行生物标志物研究来验证这一假说。该项目具有创新性。 因为它利用了两个正交的生物标志物分数；一个新的肝癌EV数字分数和有希望的血清蛋白- 基于分数。这份R21提案的长期目标是确定HCC EV、Galad、 和肝细胞癌EV-Galad数字评分用于评估肝细胞癌治疗反应并验证其在 一个独立的队列。

PROJECT SUMMARY/ABSTRACT Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Local ablation and transarterial chemoembolization (TACE) are the most commonly used treatment modality for HCC. Following treatment, patients undergo radiologic imaging for evaluation of treatment response. Assessing treatment response to local ablation or TACE is often challenging due to treatment-related nonspecific changes and definitive assessment typically requires repeated cross-sectional imaging. Similarly, there is poor radiologic-histological correlation of post-treatment tumor viability, with discordant results seen in 38% of HCC patients after local ablation or TACE. While serum alpha-fetoprotein (AFP) can aid in assessing treatment response, less than half of all patients with HCC have an elevated AFP before treatment. This limits its utility for broader implementation. The main objective of this R21 proposal is to investigate the performance of novel circulating biomarker digital scores for evaluation of HCC treatment response. Recently, Drs. Zhu (PI) and Tseng (co-Investigator) has developed a streamlined HCC extracellular vesicles (EV) digital scoring assay that couples two robust technologies, i.e., EV Click Chip for purification of HCC EVs and reverse-transcription droplet digital PCR (RT-ddPCR) for quantification of HCC-specific mRNA markers with outstanding performance for early-stage HCC detection. Besides, Dr. Yang (contact-PI) demonstrated that the GALAD score, derived from three HCC protein tumor markers (AFP-L3, AFP, and Des- carboxyprothrombin) is highly accurate for the detection of early-stage HCC. Both scores reflect tumor burden and our pilot data showed their promising performance in assessing treatment response. Thus, the central hypothesis of this R21 proposal is that pre- and post-treatment HCC EV digital score, GALAD score, and integration of two independent scores (i.e., HCC EV-GALAD digital score) can evaluate HCC treatment response. Dr. Yang and Dr. Zhu will conduct biomarker studies to test the hypothesis. This project is innovative as it leverages two orthogonal biomarker scores; a novel HCC EV digital score and promising serum protein- based score. The long-term goal of this R21 proposal is to determine the performance of HCC EV, GALAD, and HCC EV-GALAD digital scores for evaluating HCC treatment response and validate their performance in an independent cohort.