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

用于评估肝癌治疗反应的新型循环生物标志物数字评分

基本信息

批准号：
10686803
负责人：
JU DONG YANG
金额：
$ 26.89万
依托单位：
CEDARS-SINAI MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-01 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10686803
关键词：
Ablation Address Aftercare Applications Grants Area Under Curve Award Bioinformatics Biological Assay Biological Markers Biology Biometry Biotechnology California Cancer Etiology Cessation of life Chemoembolization Clinical Communication Complement Couples Data Data Analyses Detection Development Diagnosis Digital biomarker Doctor of Medicine Doctor of Philosophy Early Diagnosis Enrollment Evaluation Faculty Funding Gastroenterology Goals Grant Health Sciences Hepatology Histologic Image Image Analysis Leadership Los Angeles Malignant Neoplasms Malignant neoplasm of liver Measures Medical center Mentors Messenger RNA Modality Motivation Nature Paper Patient Monitoring Patient Recruitments Patients Performance Phase Physicians Prediction of Response to Therapy Prevention Primary carcinoma of the liver cells Prognosis Proteins Prothrombin Publishing RNA Radiology Specialty Research Research Project Grants Reverse Transcription Sampling Scientist Screening for cancer Serum Serum Proteins System Technology Testing Training Translating Tumor Burden Tumor Markers Universities Writing alpha-Fetoproteins biomarker development biomarker discovery biomarker panel cancer epidemiology cancer therapy career career development circulating biomarkers clinical practice clinical translation digital evaluation/testing extracellular vesicles innovation liquid biopsy machine learning algorithm nanotechnology platform news novel novel marker participant enrollment precision medicine prevent professor prospective radiological imaging skill acquisition skills transcriptomics treatment response tumor

项目摘要

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.

项目概要/摘要 Ju Dong Yang，医学博士、理学硕士是卡什胃肠病学和肝病学部的教员，塞缪尔雪松西奈医疗中心奥钦综合癌症研究所和健康科学助理加州大学洛杉矶分校临床教授。杨博士的长期职业目标是成为一名肝细胞癌（HCC）精准医学诊断和治疗领域的医师科学家。博士。杨的长期研究目标是将新的生物标志物发现转化为临床实践确定新型液体活检技术在癌症发展早期检测中的效用进展、治疗反应的评估和预测以及预后。为了实现他的长远目标职业目标和研究目标，杨博士制定了获得1）液体活检技能的短期职业目标生物技术，2) 前瞻性患者招募和监测，3) 纵向高级生物统计学用于大规模转录组数据分析和标记组选择的数据分析和生物信息学，以及4) 领导力和研究资助写作。 HCC 是一种生物侵袭性肿瘤，也是导致肝癌的主要原因之一全球癌症相关死亡。癌症治疗后，患者接受放射学检查以进行评估治疗反应。然而，由于治疗原因，治疗后放射学评估可能会被掩盖。相关的非特定变化。杨博士提出K08提案的主要目的是考察性能用于评估 HCC 治疗反应的新型循环生物标志物数字评分。近日，曾博士（联合主要导师）开发了一种简化的 HCC 细胞外囊泡 (EV) 数字评分测定法，结合了两种强大的技术，即用于纯化 HCC EV 的 EV Click 芯片和反转录微滴数字 PCR (RT-ddPCR) 用于定量 HCC 特异性 mRNA 标记物，具有出色的性能早期 HCC 检测的性能。杨博士证明了 GALAD 评分，源自三个 HCC 蛋白肿瘤标志物（AFP-L3、AFP 和 Des-羧基凝血酶原）对于检测早期肝癌。这两个分数都反映了肿瘤负荷，我们的试点数据显示了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 HCC EV 数字评分、GALAD 评分以及两个独立评分的整合（即 HCC EV-GALAD 数字评分）可以评估 HCC 治疗反应。杨博士将进行2期和3期生物标志物研究来测试假设。为了顺利完成该项目和职业发展，杨博士组建了一个指导委员会由 Shelly Lu, M.D.（主要导师，HCC 生物学）组成；曾宪荣博士（联合小学导师，HCC EV 技术）； Edwin Posadas，医学博士，Amit Singal，医学博士（联合导师，未来患者登记和监测），Sungyong You，博士。（生物信息学联合导师）和 Mourad Tighiouart，博士（共同导师，生物统计学）。这个K08奖将使杨博士在进行新闻报道的同时获得新闻技能新型循环肿瘤生物标志物研究，旨在解决 HCC 临床未满足的迫切需求。