Original Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Nov 7, 2011; 17(41): 4563-4571
Published online Nov 7, 2011. doi: 10.3748/wjg.v17.i41.4563
Elevated serum alpha fetoprotein levels promote pathological progression of hepatocellular carcinoma
Peng Li, Shan-Shan Wang, Hui Liu, Ning Li, Michael A McNutt, Gang Li, Hui-Guo Ding
Peng Li, Ning Li, Hui-Guo Ding, Department of Hepatology and Gastroenterology, Beijing You’an Hospital, Beijing 100069, China
Shan-Shan Wang, Gang Li, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China
Hui Liu, Department of Pathology, Beijing You’an Hospital, Beijing 100069, China
Michael A McNutt, Department of Pathology, Peking University Health Science Center, Beijing 100191, China
Author contributions: Li P and Wang SS contributed equally to this study; Liu H did immunohistochemical analysis; Li N performed the statistical analysis; McNutt MA revised the manuscript; Li G and Ding HG conceived and designed the study.
Supported by The National Natural Science Foundation of China, No. 30671856, 30772536 and 81072710; Beijing Natural Science Foundation, No. 7101006; the state key project for infectious diseases, 2008ZX10002-015, 2008ZX10002-005-3; Beijing Science and Technology Commission, Z111107058811067; and High-Level Talent Academic Leader Training Program, (2011-2-09)
Correspondence to: Gang Li, MD, Professor, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China. ligang55@bjmu.edu.cn
Telephone: +86-10-82802891 Fax: +86-10-82802891
Received: June 21, 2011
Revised: July 28, 2011
Accepted: August 4, 2011
Published online: November 7, 2011
Abstract

AIM: To investigate the biological role of alpha fetoprotein (AFP) and its clinical significance in carcinogenesis of hepatocellular carcinoma (HCC).

METHODS: Clinical analysis of HCC patients and immunohistochemical examination were conducted to evaluate the relationship between serum AFP level and patient mortality. Confocal microscopy, Western blotting, dimethylthiahzolyl-2,5-diphenyl-tetrazolium bromide, Cell Counting Kit-8 assays and flow cytometry were performed to explore the possible mechanism.

RESULTS: Among the 160 HCC patients enrolled in this study, 130 patients survived 2 years (81.25%), with a survival rate of 86.8% in AFP < 2 0 μg/L group, 88.9% in AFP 20-250 μg/L group, and 69.6% in AFP > 250 μg/L group, demonstrating a higher mortality rate in HCC patients with higher AFP levels. Surgical treatment was beneficial only in patients with low AFP levels. The mortality rate of HCC patients with high AFP levels who were treated surgically was apparently higher than those treated with conservative management. The results of immunohistochemistry showed that AFP and AFP receptor were merely expressed in tissues of HCC patients with positive serum AFP. Consistently, in vitro analysis showed that AFP and AFPS were expressed in HepG2 but not in HLE cells. AFP showed a capability to promote cell growth, and this was more apparent in HepG2 cells, in which the proliferation was increased by 3.5 folds. Cell cycle analysis showed that the percentage of HepG2 cells in S phase after exposure to AFP was modestly increased.

CONCLUSION: HCC patients with higher AFP levels show a higher mortality rate, which appears to be attributable to the growth promoting properties of AFP.

Keywords: Alpha fetoprotein; Receptor; Hepatocellular carcinoma; Mortality; Survival