Display options
Cite
Lee YT, Sun N, Kim M, et al. Circulating Tumor Cell-Based Messenger RNA Scoring System for Prognostication of Hepatocellular Carcinoma: Translating Tissue-Based Messenger RNA Profiling Into a Noninvasive Setting. Liver Transpl. 2021;doi: 10.1002/lt.26337.
Lee, Y. T., Sun, N., Kim, M., Wang, J. J., Tran, B. V., Zhang, R. Y., Qi, D., Zhang, C., Chen, P. J., Sadeghi, S., Finn, R. S., Saab, S., Han, S. B., Busuttil, R. W., Pei, R., Zhu, Y., Tseng, H. R., You, S., Yang, J. D., & Agopian, V. G. (2021). Circulating Tumor Cell-Based Messenger RNA Scoring System for Prognostication of Hepatocellular Carcinoma: Translating Tissue-Based Messenger RNA Profiling Into a Noninvasive Setting. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, . https://doi.org/10.1002/lt.26337
Lee, Yi-Te, et al. "Circulating Tumor Cell-Based Messenger RNA Scoring System for Prognostication of Hepatocellular Carcinoma: Translating Tissue-Based Messenger RNA Profiling Into a Noninvasive Setting." Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society vol. (2021). doi: https://doi.org/10.1002/lt.26337
Lee YT, Sun N, Kim M, Wang JJ, Tran BV, Zhang RY, Qi D, Zhang C, Chen PJ, Sadeghi S, Finn RS, Saab S, Han SB, Busuttil RW, Pei R, Zhu Y, Tseng HR, You S, Yang JD, Agopian VG. Circulating Tumor Cell-Based Messenger RNA Scoring System for Prognostication of Hepatocellular Carcinoma: Translating Tissue-Based Messenger RNA Profiling Into a Noninvasive Setting. Liver Transpl. 2021 Oct 18; doi: 10.1002/lt.26337. Epub 2021 Oct 18. PMID: 34664394.
Copy Download .nbib Format: NLM
Share it on

Liver Transpl. 2021 Oct 18; doi: 10.1002/lt.26337. Epub 2021 Oct 18.

Circulating Tumor Cell-Based Messenger RNA Scoring System for Prognostication of Hepatocellular Carcinoma: Translating Tissue-Based Messenger RNA Profiling Into a Noninvasive Setting.

Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society

Yi-Te Lee, Na Sun, Minhyung Kim, Jasmine J Wang, Benjamin V Tran, Ryan Y Zhang, Dongping Qi, Ceng Zhang, Pin-Jung Chen, Saeed Sadeghi, Richard S Finn, Sammy Saab, Steven-Huy B Han, Ronald W Busuttil, Renjun Pei, Yazhen Zhu, Hsian-Rong Tseng, Sungyong You, Ju Dong Yang, Vatche G Agopian

Affiliations

  1. California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA.
  2. Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Suzhou, P.R. China.
  3. Division of Cancer Biology and Therapeutics, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA.
  4. Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA.
  5. Department of Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.
  6. Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA.
  7. Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.
  8. Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA.
  9. Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA.

PMID: 34664394 DOI: 10.1002/lt.26337

Abstract

Numerous studies in hepatocellular carcinoma (HCC) have proposed tissue-based gene signatures for individualized prognostic assessments. Here, we develop a novel circulating tumor cell (CTC)-based transcriptomic profiling assay to translate tissue-based messenger RNA (mRNA) signatures into a liquid biopsy setting for noninvasive HCC prognostication. The HCC-CTC mRNA scoring system combines the NanoVelcro CTC Assay for enriching HCC CTCs and the NanoString nCounter platform for quantifying the HCC-CTC Risk Score (RS) panel in enriched HCC CTCs. The prognostic role of the HCC-CTC RS was assessed in The Cancer Genome Atlas (TCGA) HCC cohort (n = 362) and validated in an independent clinical CTC cohort (n = 40). The HCC-CTC RS panel was developed through our integrated data analysis framework of 8 HCC tissue-based gene signatures and identified the top 10 prognostic genes (discoidin domain receptor tyrosine kinase 1 [DDR1], enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase [EHHADH], androgen receptor [AR], lumican [LUM], hydroxysteroid 17-beta dehydrogenase 6[HSD17B6], prostate transmembrane protein, androgen induced 1 [PMEPA1], tsukushi, small leucine rich proteoglycan [TSKU], N-terminal EF-hand calcium binding protein 2 [NECAB2], ladinin 1 [LAD1], solute carrier family 27 member 5 [SLC27A5]) highly expressed in HCC with low expressions in white blood cells. The panel accurately discriminated overall survival in TCGA HCC cohort (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.4-2.9). The combined use of the scoring system and HCC-CTC RS panel successfully distinguished artificial blood samples spiked with an aggressive HCC cell type, SNU-387, from those spiked with PLC/PRF/5 cells (P = 0.02). In the CTC validation cohort (n = 40), HCC-CTC RS remained an independent predictor of survival (HR, 5.7; 95% CI, 1.5-21.3; P = 0.009) after controlling for Model for End-Stage Liver Disease score, Barcelona Clinic Liver Cancer stage, and CTC enumeration count. Our study demonstrates a novel interdisciplinary approach to translate tissue-based gene signatures into a liquid biopsy setting. This noninvasive approach will allow real-time disease profiling and dynamic prognostication of HCC.

Copyright © 2021 American Association for the Study of Liver Diseases.

References

  1. Nault JC, Villanueva A. Biomarkers for hepatobiliary cancers. Hepatology 2021;73(suppl 1):115-127. - PubMed
  2. Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol 2019;16:589-604. - PubMed
  3. Global Burden of Disease Liver Cancer Collaboration, Akinyemiju T, Abera S, Ahmed M, Alam N, Alemayohu MA, et al. The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: results from the Global Burden of Disease Study 2015. JAMA Oncol 1990;2017:1683-1691. - PubMed
  4. Bruix J, Reig M, Sherman M. Evidence-based diagnosis, staging, and treatment of patients with hepatocellular carcinoma. Gastroenterology 2016;150:835-853. - PubMed
  5. Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet 2003;362:1907-1917. - PubMed
  6. Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996;334:693-699. - PubMed
  7. Zucman-Rossi J, Villanueva A, Nault J-C, Llovet JM. Genetic landscape and biomarkers of hepatocellular carcinoma. Gastroenterology 2015;149:1226-1239.e4. - PubMed
  8. Schulze K, Imbeaud S, Letouzé E, Alexandrov LB, Calderaro J, Rebouissou S, et al. Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets. Nat Genet 2015;47:505-511. - PubMed
  9. Hoshida Y, Nijman SMB, Kobayashi M, Chan JA, Brunet J-P, Chiang DY, et al. Integrative transcriptome analysis reveals common molecular subclasses of human hepatocellular carcinoma. Cancer Res 2009;69:7385-7392. - PubMed
  10. Woo HG, Lee J-H, Yoon J-H, Kim CY, Lee H-S, Jang JJ, et al. Identification of a cholangiocarcinoma-like gene expression trait in hepatocellular carcinoma. Cancer Res 2010;70:3034-3041. - PubMed
  11. Cancer Genome Atlas Research Network. Electronic address wbe, Cancer Genome Cancer Genome Atlas Research Network. Comprehensive and integrative genomic characterization of hepatocellular carcinoma. Cell 2017;169:1327-1341.e23. - PubMed
  12. Silva MA, Hegab B, Hyde C, Guo B, Buckels JAC, Mirza DF. Needle track seeding following biopsy of liver lesions in the diagnosis of hepatocellular cancer: a systematic review and meta-analysis. Gut 2008;57:1592-1596. - PubMed
  13. Rockey DC, Caldwell SH, Goodman ZD, Nelson RC, Smith AD. Liver biopsy. Hepatology 2009;49:1017-1044. - PubMed
  14. Ahn JC, Teng PC, Chen PJ, Posadas E, Tseng H-R, Lu SC, Yang JD. Detection of circulating tumor cells and their implications as a novel biomarker for diagnosis, prognostication, and therapeutic monitoring in hepatocellular carcinoma. Hepatology 2021;73:422-436. - PubMed
  15. Keller L, Pantel K. Unravelling tumour heterogeneity by single-cell profiling of circulating tumour cells. Nat Rev Cancer 2019;19:553-567. - PubMed
  16. Court CM, Hou S, Winograd P, Segel NH, Li QW, Zhu Y, et al. A novel multimarker assay for the phenotypic profiling of circulating tumor cells in hepatocellular carcinoma. Liver Transpl 2018;24:946-960. - PubMed
  17. Winograd P, Hou S, Court CM, Lee Y-T, Chen P-J, Zhu Y, et al. Hepatocellular carcinoma-circulating tumor cells expressing PD-L1 are prognostic and potentially associated with response to checkpoint inhibitors. Hepatol Commun 2020;4:1527-1540. - PubMed
  18. Kalinich M, Bhan I, Kwan TT, Miyamoto DT, Javaid S, LiCausi JA, et al. An RNA-based signature enables high specificity detection of circulating tumor cells in hepatocellular carcinoma. Proc Natl Acad Sci U S A 2017;114:1123-1128. - PubMed
  19. Veldman-Jones MH, Brant R, Rooney C, Geh C, Emery H, Harbron CG, et al. Evaluating robustness and sensitivity of the NanoString Technologies nCounter platform to enable multiplexed gene expression analysis of clinical samples. Cancer Res 2015;75:2587-2593. - PubMed
  20. Geiss GK, Bumgarner RE, Birditt B, Dahl T, Dowidar N, Dunaway DL, et al. Direct multiplexed measurement of gene expression with color-coded probe pairs. Nat Biotechnol 2008;26:317-325. - PubMed
  21. Sohn BH, Shim J-J, Kim S-B, Jang KY, Kim SM, Kim JH, et al. Inactivation of hippo pathway is significantly associated with poor prognosis in hepatocellular carcinoma. Clin Cancer Res 2016;22:1256-1264. - PubMed
  22. Kim SM, Leem S-H, Chu I-S, Park Y-Y, Kim SC, Kim S-B, et al. Sixty-five gene-based risk score classifier predicts overall survival in hepatocellular carcinoma. Hepatology 2012;55:1443-1452. - PubMed
  23. Lee J-S, Chu I-S, Heo J, Calvisi DF, Sun Z, Roskams T, et al. Classification and prediction of survival in hepatocellular carcinoma by gene expression profiling. Hepatology 2004;40:667-676. - PubMed
  24. Cairo S, Armengol C, De Reynies A, Wei Y, Thomas E, Renard C-A, et al. Hepatic stem-like phenotype and interplay of Wnt/beta-catenin and Myc signaling in aggressive childhood liver cancer. Cancer Cell 2008;14:471-484. - PubMed
  25. Shin J, Kim M, Jung H-J, Cha HL, Suh-Kim H, Ahn S, et al. Characterization of developmental defects in the forebrain resulting from hyperactivated mTOR signaling by integrative analysis of transcriptomic and proteomic data. Sci Rep 2017;7:2826. - PubMed
  26. Hwang D, Rust AG, Ramsey S, Smith JJ, Leslie DM, Weston AD, et al. A data integration methodology for systems biology. Proc Natl Acad Sci U S A 2005;102:17296-17301. - PubMed
  27. Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin AA, Kim S, et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 2012;483:603-607. - PubMed
  28. Novershtern N, Subramanian A, Lawton LN, Mak RH, Haining WN, McConkey ME, et al. Densely interconnected transcriptional circuits control cell states in human hematopoiesis. Cell 2011;144:296-309. - PubMed
  29. Goldman MJ, Craft B, Hastie M, Repečka K, McDade F, Kamath A, et al. Visualizing and interpreting cancer genomics data via the Xena platform. Nat Biotechnol 2020;38:675-678. - PubMed
  30. Jan YJ, Yoon J, Chen J-F, Teng P-C, Yao NU, Cheng S, et al. A Circulating tumor cell-RNA assay for assessment of androgen receptor signaling inhibitor sensitivity in metastatic castration-resistant prostate cancer. Theranostics 2019;9:2812-2826. - PubMed
  31. Caruso S, Calatayud A-L, Pilet J, La Bella T, Rekik S, Imbeaud S, et al. Analysis of liver cancer cell lines identifies agents with likely efficacy against hepatocellular carcinoma and markers of response. Gastroenterology 2019;157:760-776. - PubMed
  32. Court CM, Hou S, Liu L, Winograd P, DiPardo BJ, Liu SX, et al. Somatic copy number profiling from hepatocellular carcinoma circulating tumor cells. NPJ Precis Oncol 2020;4:16. - PubMed
  33. Mohamed Suhaimi NA, Foong YM, Lee DY, Phyo WM, Cima I, Lee EXW, et al. Non-invasive sensitive detection of KRAS and BRAF mutation in circulating tumor cells of colorectal cancer patients. Mol Oncol 2015;9:850-860. - PubMed
  34. Zhang L, Wang X, Lai C, Zhang H, Lai M. PMEPA1 induces EMT via a non-canonical TGF-beta signalling in colorectal cancer. J Cell Mol Med 2019;23:3603-3615. - PubMed
  35. Vo Nguyen TT, Watanabe Y, Shiba A, Noguchi M, Itoh S, Kato M. TMEPAI/PMEPA1 enhances tumorigenic activities in lung cancer cells. Cancer Sci 2014;105:334-341. - PubMed
  36. Giannini G, Ambrosini MI, Di Marcotullio L, Cerignoli F, Zani M, MacKay AR, et al. EGF- and cell-cycle-regulated STAG1/PMEPA1/ERG1.2 belongs to a conserved gene family and is overexpressed and amplified in breast and ovarian cancer. Mol Carcinog 2003;38:188-200. - PubMed
  37. Rae FK, Hooper JD, Nicol DL, Clements JA. Characterization of a novel gene, STAG1/PMEPA1, upregulated in renal cell carcinoma and other solid tumors. Mol Carcinog 2001;32:44-53. - PubMed
  38. Quetglas IM, Sia D, Jiao Y, Maeda M, Castro M, Esteller M, Llovet JM. TGF-β oncogenic pathway in HCC: PMEPA1 as a biomarker of treatment response. J Hepatol 2017;66:S466. - PubMed
  39. Anderson CM, Stahl A. SLC27 fatty acid transport proteins. Mol Aspects Med 2013;34:516-528. - PubMed
  40. Gao Q, Zhang G, Zheng Y, Yang YI, Chen C, Xia J, et al. SLC27A5 deficiency activates NRF2/TXNRD1 pathway by increased lipid peroxidation in HCC. Cell Death Differ 2020;27:1086-1104. - PubMed

Publication Types

Grant support