title: Downregulation of betaine homocysteine methyltransferase (BHMT) in hepatocellular carcinoma associates with poor prognosis.
abstract: Betaine homocysteine methyltransferase (BHMT) catalyzes the synthesis of methionine using betaine and homocysteine (Hcy), which is restricted to the liver and kidney. Impaired BHMT pathway has been associated with hepatocellular carcinogenesis in Bhmt-/- mice model, and decreased BHMT was observed in a small sample of human hepatocellular carcinoma (HCC) patients. However, the prognostic significance of BHMT in HCC has not been elucidated. This study aimed to examine the expression of BHMT in HCC and investigate the relationship between its expression and prognosis of HCC patients. BHMT expression was analyzed in 68 paired HCC samples (HCC tissues vs matched adjacent non-cancerous liver tissues), 115 paraffin-embedded HCC sections (primary cohort), and 65 paraffin-embedded HCC sections (validation cohort) using immunohistochemistry (IHC). The results of IHC analysis showed that BHMT was decreased in tumorous tissues in 85.2 % (58/68) of cases compared to the corresponding adjacent non-tumorous liver tissues. Further correlation analyses indicated that the decreased BHMT expression was closely correlated with serum α-fetoprotein (AFP) (p = 0.011), tumor size (p = 0.039), and vascular invasion (p = 0.017). Moreover, HCC patients with low BHMT expression had shorter overall survival (OS) and time to recurrence (TTR) than those with high BHMT expression in both primary cohort (p < 0.0001) and validation cohort (p < 0.05) assessed by the Kaplan-Meier method. In addition, multivariate analysis showed that BHMT was an independent prognostic factor for OS and TTR in the two cohorts (all p < 0.005). Collectively, our study demonstrated that BHMT could be served as a potential prognostic marker for HCC patients.
authors.affiliation: Department of General Surgery, Qilu Hospital of Shandong University, Jinan, 250012, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Jin
authors.affiliation: Department of General Surgery, Qilu Hospital of Shandong University, Jinan, 250012, China.|Department of General Surgery, The Qingzhou City People's hospital, Qingzhou, 262500, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Gong
authors.affiliation: Department of General Surgery, The people's Hospital of LingCheng, Dezhou, 253500, China.
authors.forename: Nongguo
authors.initials: N
authors.lastname: Yang
authors.affiliation: Department of Pathology, Affiliated hospital of Guilin Medical University, Guilin, 541001, Guangxi, People's Republic of China.
authors.forename: Zhaoquan
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Pathology, Affiliated hospital of Guilin Medical University, Guilin, 541001, Guangxi, People's Republic of China.
authors.forename: Sien
authors.initials: S
authors.lastname: Zeng
authors.affiliation: Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, Guilin, 541001, Guangxi, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Qilu Hospital of Shandong University, Jinan, 250012, China. syhu1962@163.com.
authors.forename: Sanyuan
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Hepatobiliary Surgery, The people's hospital of Liuzhou, Liuzhou, 545001, Guangxi, People's Republic of China.
authors.forename: Guangdong
authors.initials: G
authors.lastname: Pan
mesh_terms: D000328:Adult; D000368:Aged; D050940:Betaine-Homocysteine S-Methyltransferase / Q000235:genetics* / Q000378:metabolism*; D014408:Biomarkers, Tumor; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D050940:Betaine-Homocysteine S-Methyltransferase
keywords: BHMT; Hepatocellular carcinoma; IHC; Prognosis