Activation of lipogenic pathway correlates with cell proliferation and poor prognosis in hepatocellular carcinoma.
OBJECTIVE
Metabolic dysregulation is one of the risk factors for the development of hepatocellular carcinoma (HCC). We investigated the activated metabolic pathway in HCC to identify its role in HCC growth and mortality.


METHODS
Gene expression profiles of HCC tissues and non-cancerous liver tissues were obtained by serial analysis of gene expression. Pathway analysis was performed to characterize the metabolic pathway activated in HCC. Suppression of the activated pathway by RNA interference was used to evaluate its role in HCC in vitro. Relation of the pathway activation and prognosis was statistically examined.


RESULTS
A total of 289 transcripts were up- or down-regulated in HCC compared with non-cancerous liver (P<0.005). Pathway analysis revealed that the lipogenic pathway regulated by sterol regulatory element binding factor 1 (SREBF1) was activated in HCC, which was validated by real-time RT-PCR. Suppression of SREBF1 induced growth arrest and apoptosis whereas overexpression of SREBF1 enhanced cell proliferation in human HCC cell lines. SREBF1 protein expression was evaluated in 54 HCC samples by immunohistochemistry, and Kaplan-Meier survival analysis indicated that SREBF1-high HCC correlated with high mortality.


CONCLUSIONS
The lipogenic pathway is activated in a subset of HCC and contributes to cell proliferation and prognosis.
Yamashita
Taro
T
Department of Gastroenterology, Kanazawa University Graduate School of Medical Science, 13-1 Takara-Machi, Kanazawa 920-8641, Japan.
Honda
Masao
M
Takatori
Hajime
H
Nishino
Ryuhei
R
Minato
Hiroshi
H
Takamura
Hiroyuki
H
Ohta
Tetsuo
T
Kaneko
Shuichi
S
D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D006801:Humans; D053208:Kaplan-Meier Estimate; D050356:Lipid Metabolism / Q000502:physiology; D050155:Lipogenesis / Q000502:physiology*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012307:Risk Factors; D015398:Signal Transduction / Q000502:physiology; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism
C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1