title: Transcriptome Analysis of WHV/c-myc Transgenic Mice Implicates Cytochrome P450 Enzyme 17A1 as a Promising Biomarker for Hepatocellular Carcinoma.
abstract: Early detection of hepatocellular carcinoma (HCC) is critical for successful treatment and favorable prognosis. To identify novel HCC biomarkers, we used the WHV/c-myc transgenic (Tg) mice, an animal model of hepatocarcinogenesis. By analyzing their gene expression profiling, we investigated differentially expressed genes in livers of wild-type and Tg mice. The cytochrome P450, family 17, subfamily A, polypeptide 1 (CYP17A1), a hepatic P450 enzyme, was revealed to be overexpressed in the liver tissues of Tg mice at both preneoplastic and neoplastic stages. Mouse-to-human validation demonstrated that CYP17A1 mRNA and protein were also significantly increased in human HCC tissues compared with paired nontumor tissues (P = 0.00041 and 0.00011, respectively). Immunohistochemical studies showed that CYP17A1 was overexpressed in 67% (58 of 87) of HCC, and strong staining of CYP17A1 was observed in well-differentiated HCCs. Consistent with this, the median serum levels of CYP17A1 were also significantly higher in patients with HCC (140.2 ng/mL, n = 776) compared with healthy controls (31.4 ng/mL, n = 366) and to those with hepatitis B virus (57.5 ng/mL, n = 160), cirrhosis (46.1 ng/mL, n = 147), lung cancer (27.4 ng/mL, n = 109), and prostate cancer (42.1 ng/mL, n = 130; all P < 0.001). Notably, the elevations were seen in most AFP-negative HCC cases. Altogether, through mouse-to-human search and validation, we found that CYP17A1 is overexpressed in HCCs and it has great potentiality as a noninvasive marker for HCC detection. These results provide a rationale for the future development and clinical application of CYP17A1 measurement to diagnose HCC more precisely. Cancer Prev Res; 9(9); 739-49. ©2016 AACR.
authors.affiliation: Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan Province, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Oncology, The 1st. Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Oncology, The 1st. Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Pu-erh Tea Science of Ministry of Education, Yunnan Agricultural University, Kunming, Yunnan Province, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ma
authors.affiliation: Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Cao
authors.affiliation: Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan Province, China.
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Biological big data, Yunan Agricultural University, Kunming, Yunnan Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan Province, China. College of Biological big data, Yunan Agricultural University, Kunming, Yunnan Province, China. dongyang@dongyang-lab.org.
authors.forename: Yang
authors.initials: Y
authors.lastname: Dong
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000201:enzymology; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D013254:Steroid 17-alpha-Hydroxylase / Q000032:analysis / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase