Reduced expression of C/EBPα protein in hepatocellular carcinoma is associated with advanced tumor stage and shortened patient survival

被引：34

作者：

Tseng, Hsi-Huang ^{[1
]}

Hwang, Yaw-Huei ^{[1
]}

Yeh, Kun-Tu ^{[2
]}

Chang, Jan-Gowth ^{[3
,4
]}

Chen, Yao-Li ^{[5
]}

Yu, Hsin-Su ^{[6
]}

机构：

[1] Natl Taiwan Univ, Inst Occupat Med & Ind Hyg, Coll Publ Hlth, Taipei 10764, Taiwan

[2] Changhua Christian Hosp, Dept Pathol, Changhua, Taiwan

[3] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Med Res, Kaohsiung, Taiwan

[4] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Lab Med, Kaohsiung, Taiwan

[5] Changhua Christian Hosp, Div Gen Surg, Dept Surg, Changhua, Taiwan

[6] Kaohsiung Med Univ, Dept Dermatol, Fac Med, Kaohsiung, Taiwan

来源：

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY | 2009年 / 135卷 / 02期

关键词：

CCAAT/enhancer binding protein alpha; Immunohistochemistry; Hepatocellular carcinoma; Survival; CCAAT/ENHANCER-BINDING-PROTEIN; ACUTE MYELOID-LEUKEMIA; CELL-PROLIFERATION; DOWN-REGULATION; ANTIPROLIFERATIVE ROLE; CEBPA MUTATIONS; LUNG-CANCER; LIVER; MICE; PATHOGENESIS;

D O I：

10.1007/s00432-008-0448-5

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

CCAAT/enhancer binding protein alpha (C/EBP alpha) is a transcription factor and a tumor suppressor. We aimed to assess its protein expression and prognostic value in human hepatocellular carcinoma (HCC). We conducted a retrospective cohort study on 50 HCC patients and performed immunohistochemistry against C/EBP alpha on tumors and adjacent nontumor specimens. Relationships of C/EBP alpha expression with clinical parameters and patient survival were analyzed. C/EBP alpha expression was not influenced by chronic alcohol exposure, viral hepatitis, or cirrhosis, but was reduced in 60% of HCC. Reduction of C/EBP alpha was associated with advanced tumor stage (P = 0.001). Patients with markedly reduced C/EBP alpha expression had a significantly shorter survival with a hazard ratio of 5.45 (95% confidence interval, 1.93-15.40; P = 0.001). C/EBP alpha may be a potential prognostic marker or therapeutic target in HCC regardless of different etiology.

引用

页码：241 / 247

页数：7

共 38 条

[1]

[Anonymous], 1997, AJCC CANC STAG MAN

[2] Tumor suppressor activity of CCAAT/enhancer binding protein α is epigenetically down-regulated in head and neck squamous cell carcinoma [J].

Bennett, Kristi L. ;

Hackanson, Bjoern ;

Smith, Laura T. ;

Morrison, Carl D. ;

Lang, James C. ;

Schuller, David E. ;

Weber, Frank ;

Eng, Charis ;

Plass, Christoph .

CANCER RESEARCH, 2007, 67 (10) :4657-4664

[3] Primary liver cancer:: Worldwide incidence and trends [J].

Bosch, FX ;

Ribes, J ;

Díaz, M ;

Cléries, R .

GASTROENTEROLOGY, 2004, 127 (05) :S5-S16

[4] Hepcidin is down-regulated in alcoholic liver injury: Implications for the pathogenesis of alcoholic liver disease [J].

Bridle, KR ;

Cheung, TK ;

Murphy, TL ;

Walters, MM ;

Anderson, GJ ;

Crawford, DHG ;

Fletcher, LM .

ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 2006, 30 (01) :106-112

[5] Immunohistochemical analysis of C/EBPα in non-small cell lung cancer reveals frequent down-regulation in stage II and IIIA tumors:: A correlative study of E3590 [J].

Costa, Daniel B. ;

Li, Sigui ;

Kocher, Olivier ;

Feins, Richard H. ;

Keller, Steven M. ;

Schiller, Joan H. ;

Johnson, David H. ;

Tenen, Daniel G. ;

Halmos, Balazs .

LUNG CANCER, 2007, 56 (01) :97-103

[6] The amino terminal and E2F interaction domains are critical for C/EBPα-mediated induction of granulopoietic development of hematopoietic cells [J].

D'Alo, F ;

Johansen, LM ;

Nelson, EA ;

Radomska, HS ;

Evans, EK ;

Zhang, P ;

Nerlov, C ;

Tenen, DG .

BLOOD, 2003, 102 (09) :3163-3171

[7] Metallothionein expression is suppressed in primary human hepatocellular carcinomas and is mediated through inactivation of CCAAT/enhancer binding protein α by phosphatidylinositol 3-kinase signaling cascade [J].

Datta, Jharna ;

Majumder, Sarmila ;

Kutay, Huban ;

Motiwala, Tasneem ;

Frankel, Wendy ;

Costa, Robert ;

Cha, Hyuk C. ;

MacDougald, Ormond A. ;

Jacob, Samson T. ;

Ghoshal, Kalpana .

CANCER RESEARCH, 2007, 67 (06) :2736-2746

[8] Adenovirus-mediated transfer of CCAAT/enhancer-binding protein-alpha identifies a dominant antiproliferative role for this isoform in hepatocytes [J].

Diehl, AM ;

Johns, DC ;

Yang, SQ ;

Lin, HZ ;

Yin, M ;

Matelis, LA ;

Lawrence, JH .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (13) :7343-7350

[9] Hepatocellular carcinoma pathogenesis: from genes to environment [J].

Farazi, Paraskevi A. ;

DePinho, Ronald A. .

NATURE REVIEWS CANCER, 2006, 6 (09) :674-687

[10] Increased hepatic cell proliferation and lung abnormalities in mice deficient in CCAAT/enhancer binding protein alpha [J].

Flodby, P ;

Barlow, C ;

Kylefjord, H ;

Åhrlund-Richter, L ;

Xanthopoulos, KG .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (40) :24753-24760

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