Metabolomics Profiles of Hepatocellular Carcinoma in a Korean Prospective Cohort: The Korean Cancer Prevention Study-II

Abstract

In the prospective Korean Cancer Prevention Study-II (KCPS-II), we investigated the application of metabolomics to differentiate subjects with incident hepatocellular carcinoma (HCC group) from subjects who remained free of cancer (control group) during a mean follow-up period of 7 years with the aim of identifying valuable metabolic biomarkers for HCC. We used baseline serum samples from 75 subjects with incident HCC and 134 age- and gender-matched cancer-free subjects. Serum metabolic profiles associated with HCC incidence were investigated via metabolomics analysis. Compared with the control group, the HCC group showed significantly higher serum levels of aspartate aminotransferase (AST), alanine aminotransferase, and γ-glutamyl transpeptidase. At baseline, compared with the control group, the HCC group showed significantly higher levels of 9 metabolites, including leucine, 5-hydroxyhexanoic acid, phenylalanine, tyrosine, arachidonic acid, and tauroursodeoxycholic acid (TUDCA), but lower levels of 28 metabolites, including oleamide, androsterone sulfate, L-palmitoylcarnitine, lysophosphatidic acid (LPA) 16:0, LPA 18:1, and lysophosphatidylcholines (lysoPC). Multiple linear regression revealed that the incidence of HCC was associated with the levels of tyrosine, AST, lysoPCs (16:1, 20:3), oleamide, 5-hydroxyhexanoic acid, androsterone sulfate, and TUDCA (adjusted = 0.514, = 0.036). This study showed the clinical relevance of the dysregulation of not only branched amino acids, aromatic amino acids, and lysoPCs but also bile acid biosynthesis and linoleic acid, arachidonic acid, and fatty acid metabolism. In addition, tyrosine, AST, lysoPCs (16:1, 20:3), oleamide, 5-hydroxyhexanoic acid, androsterone sulfate, and TUDCA were identified as independent variables associated with the incidence of HCC. .

Patterns in metabolite profile are associated with risk of more aggressive prostate cancer: A prospective study of 3,057 matched case–control sets from EPIC

“…The metabolite classes included in treelet components 1 and 3 are structural components of cell membranes, and along with the related enzymes and intermediates they are involved in proliferation, cell signaling and cell survival, and thus may play key roles in carcinogenesis, progression and migration of tumors. 20,21,28 Their potential association may apply to cancer in general rather than being prostate cancer-specific; some prospective studies have reported lower risk of breast cancer, 9,29 colorectal cancer, 30 hepatocellular carcinoma 31,32 and pancreatic cancer 33 in relation to higher levels of phosphatidylcholines and related metabolites, while another study did not observe an association between the few included phospholipids and breast cancer risk. 34 Involvement in shared metabolic pathways may also explain the grouping of metabolites in treelet component 2.…”

SILVER SULFATE (Ag2SO4): MOLECULAR ANALYSIS AND ION TRANSPORT

“…Perak sulfat (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) merupakan senyawa ion dari perak dengan rumus Ag2SO4, yang digunakan dalam penyepuhan perak (silver plating) dan pengganti tanpa noda untuk perak nitrat. Garam sulfat ini stabil di bawah kondisi penggunaan dan penyimpanan biasa, meskipun ia menjadi gelap pada pajanan terhadap udara atau cahaya.…”

“…Perak Sulfat (Ag2SO4) (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) memiliki konduktivitas (1)(2)(3)(4)(5)(6)(7)(8)(9)(10) . Besarnya nilai konduktivitas (1-10) ditentukan oleh konsentrasi elektrolit.…”

“…Garam sulfat ini stabil di bawah kondisi penggunaan dan penyimpanan biasa, meskipun ia menjadi gelap pada pajanan terhadap udara atau cahaya. Perak Sulfat (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) mengalami interaksi molekul dalam pelarut Air. Berat molekul senyawa ini yaitu 311,799 gr/mol dengan tampilan kristal tidak berwarna.…”

“…Kelarutannya dalam air 0,79 gr/100 mL (20 o C) dan dapat larut juga dalam pelarut asam nitrat. Secara termokimia, perak sulfat (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) memiliki entalpi pembentukan standar, ΔfHo298 -715 kJ/mol dan entropi molar standar, So298 16,74 kJ/mol. Perak sulfat (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) tidak mudah terbakar.Perak Sulfat (Ag2SO4) (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) memiliki konduktivitas (1)(2)(3)(4)(5)(6)(7)(8)(9)(10) .…”