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

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，MD，MS是Karsh胃肠病学和肝病学系的一名教师， 雪松西奈医学中心的Oschin综合癌症研究所和健康科学助理 洛杉矶的加州大学的临床教授。杨博士的长期职业目标是成为一名 肝细胞癌（HCC）的精准医学诊断和治疗的医生科学家。博士 Yang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实用性， 进展、治疗反应的评估和预测以及预后。为了实现他的长期目标 职业目标和研究目标，杨博士建立了短期职业目标，获得技能1）液体活检 生物技术，2）前瞻性患者招募和监测，3）纵向研究的高级生物统计学 用于大规模转录组数据分析和标记物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是一种生物学侵袭性肿瘤，并且是HCC的主要原因之一。 全球癌症相关死亡人数。癌症治疗后，患者接受放射学检查进行评估， 治疗反应。然而，治疗后的放射学评估可能由于治疗而模糊- 相关的非特定变化。杨博士的K 08提案的主要目的是研究 新的循环生物标志物数字评分用于评估HCC治疗反应。最近，曾医生 （Co-Primary mentor）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和逆转录的EV Click芯片 微滴数字PCR（RT-ddPCR）用于定量HCC特异性mRNA标志物， 用于早期HCC检测的性能。杨博士证明，GALAD评分，来自三个 HCC蛋白质肿瘤标志物（AFP-L3、AFP和去羧基凝血酶原）对于检测HCC具有高度准确性。 早期HCC这两个评分反映了肿瘤负荷，我们的初步数据显示了它们在肿瘤治疗中的良好表现。 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HCC EV数字评分、GALAD评分和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，以测试 假说.为了顺利完成项目和职业发展，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）; Hsian-Rong Tseng，博士 （HCC EV技术联合主要导师）; Edwin波萨达斯，医学博士，Amit Singal，医学博士（共同导师，预期 患者入组和监测），Sungyong You，Ph.D.（共同导师，生物信息学）和Mourad Mesiouart， 博士（生物统计学共同导师）。这个K 08奖将使杨博士获得新闻技能，同时进行一个 一项新的循环肿瘤生物标志物研究，以解决HCC中迫切的临床未满足的需求。