TY - JOUR
T1 - Gene expression signature of the gross morphology in hepatocellular carcinoma
AU - Murakata, Ayano
AU - Tanaka, Shinji
AU - Mogushi, Kaoru
AU - Yasen, Mahmut
AU - Noguchi, Norio
AU - Irie, Takumi
AU - Kudo, Atsushi
AU - Nakamura, Noriaki
AU - Tanaka, Hiroshi
AU - Arii, Shigeki
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2011/1
Y1 - 2011/1
N2 - Objective: To evaluate the gene expression signature of hepatocellular carcinoma (HCC) in relation to the gross morphology. Background: Eggel's nodular type of HCC is morphologically subclassified into the single nodular (SN) type, the single nodular type with extranodular growth (SNEG), and the confluent multinodular (CM) type, but their biomolecular differences remain unclear. Methods: The clinicopathological characteristics and genome-wide gene expressions were analyzed in 275 patients with nodular-type HCC (124 SN-type, 91 SNEG-type, and 60 CM-type) who received curative hepatectomy. Results: Significantly poor prognosis was recognized in CM types in overall survival (P = 0.0020) and recurrence-free survival (P = 0.0066). Analysis of the genome-wide expression patterns revealed significant difference of CM-type HCC from either SN-or SNEG-type HCC. In particular, a stem cell marker EpCAM was dominantly expressed in CM-type HCC. Immunohistochemical studies confirmed the specific expression of EpCAM in HCC cancer cells of CM type. In multivariate analysis, the gross morphology of CM type was significantly associated with EpCAM expression (P = 0.0092), α-fetoprotein (P = 0.0424), "lens culinaris agglutinin-reactive fraction of α-fetoprotein" level (P = 0.0288), and the portal vein invasion (P = 0.0150). Furthermore, EpCAM was predictive for poor prognosis in overall and recurrence-free survivals of patients with CM-type HCC (P = 0.0082 and P = 0.0043, respectively). Conclusion: Our studies suggest that the distinct signature of gene expression is closely related to morphological progression in HCC. Especially, EpCAM might play a critical role in the aggressiveness of CM-type HCC.
AB - Objective: To evaluate the gene expression signature of hepatocellular carcinoma (HCC) in relation to the gross morphology. Background: Eggel's nodular type of HCC is morphologically subclassified into the single nodular (SN) type, the single nodular type with extranodular growth (SNEG), and the confluent multinodular (CM) type, but their biomolecular differences remain unclear. Methods: The clinicopathological characteristics and genome-wide gene expressions were analyzed in 275 patients with nodular-type HCC (124 SN-type, 91 SNEG-type, and 60 CM-type) who received curative hepatectomy. Results: Significantly poor prognosis was recognized in CM types in overall survival (P = 0.0020) and recurrence-free survival (P = 0.0066). Analysis of the genome-wide expression patterns revealed significant difference of CM-type HCC from either SN-or SNEG-type HCC. In particular, a stem cell marker EpCAM was dominantly expressed in CM-type HCC. Immunohistochemical studies confirmed the specific expression of EpCAM in HCC cancer cells of CM type. In multivariate analysis, the gross morphology of CM type was significantly associated with EpCAM expression (P = 0.0092), α-fetoprotein (P = 0.0424), "lens culinaris agglutinin-reactive fraction of α-fetoprotein" level (P = 0.0288), and the portal vein invasion (P = 0.0150). Furthermore, EpCAM was predictive for poor prognosis in overall and recurrence-free survivals of patients with CM-type HCC (P = 0.0082 and P = 0.0043, respectively). Conclusion: Our studies suggest that the distinct signature of gene expression is closely related to morphological progression in HCC. Especially, EpCAM might play a critical role in the aggressiveness of CM-type HCC.
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U2 - 10.1097/SLA.0b013e3181f9bc00
DO - 10.1097/SLA.0b013e3181f9bc00
M3 - Article
C2 - 21233610
AN - SCOPUS:78751603857
VL - 253
SP - 94
EP - 100
JO - Annals of Surgery
JF - Annals of Surgery
SN - 0003-4932
IS - 1
ER -