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

• 批准号: 10370966
• 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
• 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/10370966
• 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; Doctor of Medicine; Doctor of Philosophy; Early Diagnosis; Enrollment; Evaluation; Faculty; Funding; Gastroenterology; Goals; Gold; Grant; Health Sciences; Hepatology; Histologic; Image; Image Analysis; Institutes; 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; 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; Yang; acarboxy prothrombin; alpha-Fetoproteins; base; 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; skills; standard care; transcriptomics; treatment response; tumor; 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; Doctor of Medicine; Doctor of Philosophy; Early Diagnosis; Enrollment; Evaluation; Faculty; Funding; Gastroenterology; Goals; Gold; Grant; Health Sciences; Hepatology; Histologic; Image; Image Analysis; Institutes; 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; 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; Yang; acarboxy prothrombin; alpha-Fetoproteins; base; 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; skills; standard care; transcriptomics; treatment response; tumor

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.

项目摘要/摘要 Ju dong Yang，医学博士，MS是胃肠病学和肝病学和塞缪尔的Karsh分部的教职员工 Cedars-Sinai医学中心的Oschin综合癌症研究所和健康科学助理 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个 基于精密医学的肝癌（HCC）的医师科学家。博士 杨的长期研究目标是将新颖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早期发现癌症发展和 治疗反应和预后的进展，评估和预测。实现他的长期 职业目标和研究目标，杨博士在1）液体活检中建立了获得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）纵向的高级生物统计学 数据分析以及用于大型转录组数据分析和标记面板选择的生物信息学，以及4） 领导力和研究赠款写作。 HCC是一种生物学上攻击性的肿瘤，是 全球与癌症有关的死亡。癌症治疗后，患者接受放射学检查进行评估 治疗反应。但是，由于治疗，治疗后放射学评估可能会被遮盖 相关的非特异性变化。杨博士K08提案的主要目的是调查性能 用于评估HCC治疗反应的新型循环生物标志物数字评分。最近，Tseng博士 （共同主要导师）开发了一种简化的HCC细胞外囊泡（EV）数字评分测定法 夫妻两种强大的技术，即，ev单击芯片以净化HCC EV和反向转录 液滴数字PCR（RT-DDPCR），用于定量具有未出色的HCC特异性mRNA标记 早期HCC检测的性能。杨博士证明了galad得分，源自三个 HCC蛋白肿瘤标记物（AFP-L3，AFP和DES-CarboxyProthrombin）非常准确地检测 早期HCC。两种分数反映了肿瘤负担，我们的飞行员数据表明​​他们有希望的表现 评估治疗反应。因此，该项目的核心假设是治疗前和治疗后HCC EV数字得分，galad得分和两个独立分数的集成（即HCC EV-GALAD数字得分） 可以评估HCC治疗反应。杨博士将进行第2阶段和3阶段的生物标志物研究，以测试 假设。为了成功完成项目和职业发展，杨博士集会了 由M.D. Shelly Lu组成的指导委员会（HCC生物学主要导师）； Hsian-Rong Tseng博士 （HCC EV技术联合主导）；医学博士Edwin Posadas，医学博士 患者入学和监测），Sungyong You，Ph.D。 （同事，生物信息学）和Mourad Tighiouart， 博士（生物统计学）。该K08奖将允许杨博士在进行一次新闻技能 新型循环肿瘤生物标志物研究，以满足HCC中紧急临床未满足的需求。