LOH analysis of genes around D4S2964 identifies ARD1B as a prognostic predictor of hepatocellular carcinoma.
OBJECTIVE
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).


CONCLUSIONS
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.
Huang
Guo-Liang
GL
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, 651 Dongfeng East Road, Guangzhou, Guangdong Province, China.
Li
Bin-Kui
BK
Zhang
Mei-Yin
MY
Zhang
Hui-Zhong
HZ
Wei
Rong-Rong
RR
Yuan
Yun-Fei
YF
Shi
Ming
M
Chen
Xiao-Qian
XQ
Huang
Long
L
Li
An-Hua
AH
Huang
Bi-Jun
BJ
Li
Hong-Hua
HH
Wang
Hui-Yun
HY
D020727:ADP-Ribosylation Factors / Q000378:metabolism; D000123:Acetyltransferases / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D005260:Female; D005355:Fibrosis / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D019656:Loss of Heterozygosity; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D063209:N-Terminal Acetyltransferase A; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D051116:Receptors, Scavenger / Q000378:metabolism; D058112:Septins
D018797:Cell Cycle Proteins; D051907:Lysosomal Membrane Proteins; D051116:Receptors, Scavenger; C074299:SCARB2 protein, human; D000123:Acetyltransferases; D063209:N-Terminal Acetyltransferase A; C511250:NAA11 protein, human; C116687:ARF3 protein, human; C496549:SEPTIN11 protein, human; D058112:Septins; D020727:ADP-Ribosylation Factors