2. Academic Validation
  3. Urinary Metabolites Diagnostic and Prognostic of Intrahepatic Cholangiocarcinoma

Urinary Metabolites Diagnostic and Prognostic of Intrahepatic Cholangiocarcinoma

  • Cancer Epidemiol Biomarkers Prev. 2019 Oct;28(10):1704-1711. doi: 10.1158/1055-9965.EPI-19-0453.
Majda Haznadar 1,  Christopher M Diehl  # 1,  Amelia L Parker  # 1,  Kristopher W Krausz 2,  Elise D Bowman 1,  Siritida Rabibhadana 3,  Marshonna Forgues 1,  Vajarabhongsa Bhudhisawasdi 3,  Frank J Gonzalez 2,  Chulabhorn Mahidol 3 4,  Anuradha Budhu 1,  Xin W Wang 1,  Mathuros Ruchirawat 4 5,  Curtis C Harris 6
Affiliations

Affiliations

  • 1 Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
  • 2 Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
  • 3 Laboratory of Chemical Carcinogenesis, Chulabhorn Research Institute, Bangkok, Thailand.
  • 4 Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok, Thailand.
  • 5 Center of Excellence on Environmental Health and Toxicology, Office of Higher Education Commission, Ministry of Education, Bangkok, Thailand.
  • 6 Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland. harrisc@mail.nih.gov mathuros@cri.or.th.
  • # Contributed equally.
PMID: 31358519 DOI: 10.1158/1055-9965.EPI-19-0453
Abstract

Background: Liver Cancer is the second leading cause of cancer-related deaths worldwide. With a predicted 2.4-fold rise in liver Cancer incidence by 2020, there is an urgent need for early, inexpensive diagnostic biomarkers to deploy in the clinic.

Methods: We employed ultraperformance liquid chromatography tandem mass-spectrometry (UPLC/MS-MS) for the quantitation of four metabolites, creatine riboside (CR), N-acetylneuraminic acid (NANA), cortisol sulfate, and a lipid molecule designated as 561+, in urine samples from the NCI-MD cohort comprising 98 hepatocellular carcinoma (HCC) cases, 101 high-risk subjects, and 95 controls. Validation was carried out in the TIGER-LC cohort [n = 370 HCC and intrahepatic cholangiocarcinoma (ICC) cases, 471 high-risk subjects, 251 controls], where ICC, the second most common primary hepatic malignancy, is highly prevalent. Metabolite quantitation was also conducted in TIGER-LC tissue samples (n = 48 ICC; n = 51 HCC).

Results: All profiled metabolites were significantly increased in liver Cancer when compared with high-risk subjects and controls in the NCI-MD study. In the TIGER-LC cohort, the four-metabolite profile was superior at classifying ICC than a clinically utilized marker, CA19-9, and their combination led to a significantly improved model (AUC = 0.88, P = 4E-8). Metabolites CR and NANA were significantly elevated in ICC when compared with HCC cases in both urine and tissue samples. High levels of CR were associated with poorer prognosis in ICC.

Conclusions: Four metabolites are significantly increased in HCC and ICC and are robust at classifying ICC in combination with the clinically utilized marker CA19-9.

Impact: Noninvasive urinary metabolite biomarkers hold promise for diagnostic and prognostic evaluation of ICC.

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