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

项目摘要/摘要 杨菊栋，医学博士，医学硕士，卡什消化肝病分部和塞缪尔医院的教员。 锡达斯-西奈医学中心的奥辛综合癌症研究所和一名健康科学助理 加州大学洛杉矶分校的临床教授。杨博士的长期职业目标是成为一名 以精确医学为基础的肝细胞癌诊断和治疗方面的内科科学家。Dr。 杨的长期研究目标是通过以下方式将新的生物标记物发现转化为临床实践 确定新的液体活组织检查技术在癌症发生和早期检测中的作用 治疗反应和预后的进展、评估和预测。为了实现他的长期 职业目标和研究目标，杨医生设定了短期职业目标，即获得液体活组织检查技能 生物技术，2)预期的患者招募和监测，3)纵向的高级生物统计 数据分析和生物信息学，用于大规模转录数据分析和标记小组选择，以及4) 领导力和研究拨款的撰写。肝癌是一种具有生物侵袭性的肿瘤，是引起 全球与癌症相关的死亡人数。癌症治疗后，患者接受放射检查以进行评估。 治疗反应。然而，治疗后的放射学评估可能会因为治疗- 相关的非特定更改。杨博士K08提案的主要目标是调查性能 新的循环生物标记物数字评分用于评估肝癌治疗反应。最近，曾博士 (共同初级导师)开发了一种简化的肝癌细胞外小泡(EV)数字评分测试， 结合两种强大的技术，即用于肝癌EV纯化和反转录的EV点击芯片 滴状数字聚合酶链式反应(RT-ddPCR)定量检测肝细胞癌特异性基因标记物 用于早期肝细胞癌检测的性能。杨博士证明了Galad评分，源于三个 肝癌蛋白肿瘤标志物(AFP-L3、AFP和DES-羧基凝血酶原)对检测肝癌具有很高的准确性 早期肝细胞癌。这两个分数都反映了肿瘤负担，我们的试点数据显示，它们在 评估治疗反应。因此，该项目的中心假设是治疗前和治疗后的肝癌 EV数字分数、Galad分数和两个独立分数的集成(即，HCC EV-Galad数字分数) 可以评估肝细胞癌的治疗反应。杨博士将进行第二阶段和第三阶段的生物标志物研究，以测试 假设。为了顺利完成项目和事业发展，杨博士组装了一个 导师委员会成员：陆秀丽，医学博士(主要导师，肝癌生物学)；曾宪荣，博士。 (联合初级导师，HCC EV技术)；Edwin Posadas，医学博士，Amit Singal，医学博士(联合导师，预期 患者登记和监测)、游胜勇博士(生物信息学联合导师)和Mourad Tighiouart， 博士(生物统计学共同导师)。这一K08奖项将允许杨博士在进行一次 新的循环肿瘤生物标记物研究，以解决肝细胞癌临床上未得到满足的迫切需求。

PROJECT SUMMARY/ABSTRACT Ju Dong Yang, MD, MS is a faculty in the Karsh Division of Gastroenterology and Hepatology and the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center and a health sciences assistant clinical professor at the University of California, Los Angeles. Dr. Yang`s long-term career goal is to become a physician-scientist in precision medicine-based diagnosis and treatment of hepatocellular carcinoma (HCC). Dr. Yang`s long-term research objective is to translate novel biomarker discovery into clinical practice by determining the utility of novel liquid biopsy technology in early detection of cancer development and progression, assessment and prediction of treatment response, and prognosis. To achieve his long-term career goal and research objectives, Dr. Yang set up short-term career goals of gaining skills in 1) liquid biopsy biotechnologies, 2) prospective patient recruitment and monitoring, 3) advanced biostatistics for longitudinal data analysis, and bioinformatics for large scale transcriptomic data analysis and marker panel selection, and 4) leadership and research grant writing. HCC is a biologically aggressive tumor and one of the leading causes of cancer-related deaths worldwide. Following cancer treatment, patients undergo radiologic tests for evaluation of treatment response. However, post-treatment radiologic assessment could be obscured due to treatment- related non-specific changes. The main objective of Dr. Yang's K08 proposal is to investigate the performance of novel circulating biomarker digital scores for evaluation of HCC treatment response. Recently, Dr. Tseng (Co-Primary mentor) 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. Dr. Yang 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 the project 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 will conduct phase 2 and 3 biomarker studies to test the hypothesis. For successful completion of the project and career development, Dr. Yang assembled a mentoring committee consisting of Shelly Lu, M.D. (Primary mentor, HCC biology); Hsian-Rong Tseng, Ph.D. (Co-Primary mentor, HCC EV technology); Edwin Posadas, M.D., Amit Singal, M.D. (Co-mentor, prospective patient enrollment and monitoring), Sungyong You, Ph.D. (Co-mentor, bioinformatics) and Mourad Tighiouart, Ph.D. (Co-mentor, biostatistics). This K08 award will allow Dr. Yang to gain news skills while conducting a novel circulating tumor biomarker study to address urgent clinical unmet needs in HCC.