Program Official

Principal Investigator

Xianghong Jasmine
Zhou
Awardee Organization

University Of California Los Angeles
United States

Fiscal Year
2022
Activity Code
U01
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

The UCLA Center in Early Detection of Liver Cancer

Hepatocellular carcinoma (HCC) is a major cause of death in cirrhotic patients. This neoplasm is associated with liver cirrhosis in more than 90% of cases. A method of detecting HCC accurately in its early stages would greatly improve our ability to manage and treat the disease. The UCLA Center aims to develop an effective and affordable blood-based method for the early detection of liver cancer. Our team consists of translational and clinical researchers with multi-disciplinary expertise in the areas of early detection, biomarkers, cancer surveillance, imaging, and biorepositories. We will focus on circulating tumor DNA (ctDNA) in the blood. ctDNA carryies cancer-specific genetic and epigenetic aberrations, which enable a noninvasive `liquid biopsy' for cancer diagnosis. Our diagnostic test is based on the DNA methylation patterns of cfDNA. Our integrated computational and experimental technologies can significantly boost the diagnostic power while dramatically reducing the cost. We have the following aims: (1) We will establish a longitudinal cohort of cirrhotic patients. The cirrhotic patients will be subject to ultrasound imaging screening and blood sample collection every 6 months. The UCLA liver clinic sees ~1200 cirrhotic patients per year. (2) We will establish a state-of-the-art biospecimen repository that includes plasma from individuals in the cohort, tissue from liver tumors after resection, and cirrhotic lesions after liver transplantation. (3) We will perform Phase 2 clinical assay validation and Phase 3 early detection validation for the diagnostic test. (4) We will contribute to the collaborative trans-network activities.

Publications

  • Li S, Zeng W, Ni X, Zhou Y, Stackpole ML, Noor ZS, Yuan Z, Neal A, Memarzadeh S, Garon EB, Dubinett SM, Li W, Zhou XJ. cfTrack: A Method of Exome-Wide Mutation Analysis of Cell-free DNA to Simultaneously Monitor the Full Spectrum of Cancer Treatment Outcomes Including MRD, Recurrence, and Evolution. Clinical cancer research : an official journal of the American Association for Cancer Research. 2022 May 2;28(9):1841-1853. PMID: 35149536
  • Benhammou JN, Rich NE, Cholankeril G, Zhang P, Zeng W, Rao S, Tayob N, National Cancer Institute’s Translational Liver Consortium Early-Career Working Group, Li W, Wu X, Feng S, Fujiwara N, Meng X, Zhu S, Zaidi S. DETECT: Development of Technologies for Early HCC Detection. Gastroenterology. 2022 Jul;163(1):21-27. Epub 2022 Mar 23. PMID: 35339460
  • Li W, Zhou XJ. Methylation extends the reach of liquid biopsy in cancer detection. Nature reviews. Clinical oncology. 2020 Nov;17(11):655-656. PMID: 32732909
  • An Q, Hu Y, Li Q, Chen X, Huang J, Pellegrini M, Zhou XJ, Rettig M, Fan G. The size of cell-free mitochondrial DNA in blood is inversely correlated with tumor burden in cancer patients. Precision clinical medicine. 2019 Sep;2(3):131-139. Epub 2019 Oct 1. PMID: 31598384
  • Hu R, Zhou XJ, Li W. Computational Analysis of High-Dimensional DNA Methylation Data for Cancer Prognosis. Journal of computational biology : a journal of computational molecular cell biology. 2022 Aug;29(8):769-781. Epub 2022 Jun 6. PMID: 35671506
  • Stackpole ML, Zeng W, Li S, Liu CC, Zhou Y, He S, Yeh A, Wang Z, Sun F, Li Q, Yuan Z, Yildirim A, Chen PJ, Winograd P, Tran B, Lee YT, Li PS, Noor Z, Yokomizo M, Ahuja P, Zhu Y, Tseng HR, Tomlinson JS, Garon E, French S, Magyar CE, Dry S, Lajonchere C, Geschwind D, Choi G, Saab S, Alber F, Wong WH, Dubinett SM, Aberle DR, Agopian V, Han SB, Ni X, Li W, Zhou XJ. Cost-effective methylome sequencing of cell-free DNA for accurately detecting and locating cancer. Nature communications. 2022 Sep 29;13(1):5566. PMID: 36175411
  • Pinto Marques H, Gomes da Silva S, De Martin E, Agopian VG, Martins PN. Emerging biomarkers in HCC patients: Current status. International journal of surgery (London, England). 2020 Oct;82S:70-76. Epub 2020 Apr 25. PMID: 32344023
  • Kadara H, Tran LM, Liu B, Vachani A, Li S, Sinjab A, Zhou XJ, Dubinett SM, Krysan K. Early Diagnosis and Screening for Lung Cancer. Cold Spring Harbor perspectives in medicine. 2021 Sep 1;11. (9). PMID: 34001525
  • Sun N, Zhang C, Lee YT, Tran BV, Wang J, Kim H, Lee J, Zhang RY, Wang JJ, Hu J, Zhang Z, Alsudaney MS, Hou KC, Tang H, Zhang TX, Liang IY, Zhou Z, Chen M, Yeh AH, Li W, Zhou XJ, Chang HR, Han SB, Sadeghi S, Finn RS, Saab S, Busuttil RW, Noureddin M, Ayoub WS, Kuo A, Sundaram V, Al-Ghaieb B, Palomique J, Kosari K, Kim IK, Todo T, Nissen NN, Tomasi ML, You S, Posadas EM, Wu JX, Wadehra M, Sim MS, Li Y, Wang HL, French SW, Lu SC, Wu L, Pei R, Liang L, Yang JD, Agopian VG, Tseng HR, Zhu Y. HCC EV ECG score: An extracellular vesicle-based protein assay for detection of early-stage hepatocellular carcinoma. Hepatology (Baltimore, Md.). 2023 Mar 1;77(3):774-788. Epub 2023 Feb 17. PMID: 35908246
  • Court CM, Hou S, Liu L, Winograd P, DiPardo BJ, Liu SX, Chen PJ, Zhu Y, Smalley M, Zhang R, Sadeghi S, Finn RS, Kaldas FM, Busuttil RW, Zhou XJ, Tseng HR, Tomlinson JS, Graeber TG, Agopian VG. Somatic copy number profiling from hepatocellular carcinoma circulating tumor cells. NPJ precision oncology. 2020 Jul 2;4:16. doi: 10.1038/s41698-020-0123-0. eCollection 2020. PMID: 32637655
  • Sun N, Lee YT, Zhang RY, Kao R, Teng PC, Yang Y, Yang P, Wang JJ, Smalley M, Chen PJ, Kim M, Chou SJ, Bao L, Wang J, Zhang X, Qi D, Palomique J, Nissen N, Han SB, Sadeghi S, Finn RS, Saab S, Busuttil RW, Markovic D, Elashoff D, Yu HH, Li H, Heaney AP, Posadas E, You S, Yang JD, Pei R, Agopian VG, Tseng HR, Zhu Y. Purification of HCC-specific extracellular vesicles on nanosubstrates for early HCC detection by digital scoring. Nature communications. 2020 Sep 7;11(1):4489. PMID: 32895384
  • Li S, Noor ZS, Zeng W, Stackpole ML, Ni X, Zhou Y, Yuan Z, Wong WH, Agopian VG, Dubinett SM, Alber F, Li W, Garon EB, Zhou XJ. Sensitive detection of tumor mutations from blood and its application to immunotherapy prognosis. Nature communications. 2021 Jul 7;12(1):4172. PMID: 34234141
  • Li JR, Tong CY, Sung TJ, Kang TY, Zhou XJ, Liu CC. CMEP: a database for circulating microRNA expression profiling. Bioinformatics (Oxford, England). 2019 Sep 1;35(17):3127-3132. PMID: 30668638