Copyright
©2010 Baishideng. All rights reserved.
LOH analysis of genes around D4S2964 identifies ARD1B as a prognostic predictor of hepatocellular carcinoma
Guo-Liang Huang, Bin-Kui Li, Mei-Yin Zhang, Hui-Zhong Zhang, Rong-Rong Wei, Yun-Fei Yuan, Ming Shi, Xiao-Qian Chen, Long Huang, An-Hua Li, Bi-Jun Huang, Hong-Hua Li, Hui-Yun Wang
Guo-Liang Huang, Mei-Yin Zhang, Rong-Rong Wei, Xiao-Qian Chen, Long Huang, Bi-Jun Huang, Hui-Yun Wang, State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, 651 Dongfeng East Road, Guangzhou 510060, Guangdong Province, China
Bin-Kui Li, Yun-Fei Yuan, Ming Shi, Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-Sen University, 651 Dongfeng East Road, Guangzhou 510060, Guangdong Province, China
Hui-Zhong Zhang, Department of Pathology, Cancer Center, Sun Yat-Sen University, 651 Dongfeng East Road, Guangzhou 510060, Guangdong Province, China
An-Hua Li, Department of Ultrasound and Electrocardiogram, Cancer Center, Sun Yat-Sen University, 651 Dongfeng East Road, Guangzhou 510060, Guangdong Province, China
Hong-Hua Li, Department of Molecular Genetics, Microbiology and Immunology/The Cancer Institute of New Jersey, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854, United States
Author contributions: Huang GL, Zhang MY, Wei RR, Chen XQ and Huang L performed the experiment; Huang GL and Wei RR analyzed the data; Li BK, Yuan YF and Shi M provided samples and clinical information; Zhang HZ pathologically re-diagnosed HCC; Li AH provided ultrasound diagnosis of hepatocirrhosis; Huang BJ and Li HH gave vital comments; Li HH designed the primers and probes of SNP microarray; Huang GL, Li HH and Wang HY wrote the paper; Wang HY designed and guided the research.
Supported by National Natural Science Foundation of China, No. 30772491 to Wang HY; and partially supported by Research Fund of State Key Laboratory of Oncology in South China to Wang HY
Correspondence to: Hui-Yun Wang, MD, PhD, Professor, State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, 651 Dongfeng East Road, Room 617, Guangzhou 510060, Guangdong Province, China. wanghyun@mail.sysu.edu.cn
Telephone: +86-20-87343308 Fax: +86-20-87343308
Received: January 10, 2010
Revised: February 14, 2010
Accepted: February 21, 2010
Published online: April 28, 2010
AIM: To investigate genes around the locus D4S2964 affected by loss of heterozygosity (LOH) and their clinical implications.
METHODS: Four hundred and forty single nucleotide polymorphisms (SNPs) located at 49 genes around D4S2964 were selected from the National Center for Biotechnology Information website for the SNPs microarray fabrication. LOH of SNPs markers in 112 cases of hepatocellular carcinoma (HCC) tissues and paired adjacent liver tissues were investigated by the SNPs microarray. The correlation between allelic losses with clinicopathological features and overall survival was analyzed.
RESULTS: A fine map of LOH of SNPs in genes around D4S2964 was plotted. The average frequency of LOH in genes was 0.39. A correlation between cirrhosis and the FAL index (fractional allelic loss) was found (P = 0.0202). Larger tumor size was found to be significantly associated with LOH in genes ADP-ribosyltransferase 3 (ART3), nucleoporin 54 kDa (NUP54), scavenger receptor class B, member 2 (SCARB2) and coiled-coil domain containing 158 (CCDC158) (P = 0.043, P = 0.019, P = 0.001, P = 0.037, respectively). Kaplan-Meier analysis showed that patients with LOH in ARD1 homolog B (ARD1B) and septin 11 (SEPT11) had a significantly lower survival rate than those with retention (P = 0.021 and P = 0.004, respectively). A Cox regression model suggested that LOH in ARD1B and SEPT11, respectively, were predictors of the overall survival in HCC (P = 0.006 and P = 0.026, respectively).
CONCLUSION: LOH in genes around D4S2964 may play an important role in HCC development and progression. LOH in ARD1B and SEPT11 could serve as novel prognostic predictors in HCC patients.
