Amplification of chromosome 21q22.3 harboring trefoil factor family genes in liver fluke related cholangiocarcinoma is associated with poor prognosis.
OBJECTIVE
To determine allelic imbalance on chromosomal region 21q22-qter including trefoil factor family genes (TFF) in cholangiocarcinoma (CCA) patients and analyze the correlation between allelic imbalances and clinicopathological parameters.


METHODS
Quantitative PCR amplification was performed on four microsatellite markers and trefoil factor family genes (TFF1, TFF2, and TFF3) using a standard curve and SYBR Green I dye method. The relative copy number was determined by DNA copy number of tested locus to reference locus. The relative copy number was interpreted as deletion or amplification by comparison with normal reference range. Associations between allelic imbalance and clinicopathological parameters of CCA patients were evaluated by chi(2)-tests. Kaplan-Meier method was used to analyze survival.


RESULTS
The frequencies of amplification at D21S1890, D21S1893, and TFF3 were 32.5%, 30.0%, and 28.7%, respectively. Patients who had amplification at regions covering D21S1893, D21S1890, and TFF showed poor prognosis, whereas patients who had deletion showed favorable prognosis (mean: 51.7 wk vs 124.82 wk, P = 0.012). Multivariate Cox regression analysis revealed that amplification of D21S1893, D21S1890 and TFF, blood vessel invasion, and staging were associated with poor prognosis.


CONCLUSIONS
D21S1893-D21S1890 region may harbor candidate genes especially TFF and serine protease family, which might be involved in tumor invasion and metastasis contributing to poor survival. The amplification in this region may be used as a prognostic marker in the treatment of CCA patients.
Muenphon
Kanuengnuch
K
Department of Clinical Chemistry, Center for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand.
Limpaiboon
Temduang
T
Jearanaikoon
Patcharee
P
Pairojkul
Chawalit
C
Sripa
Banchob
B
Bhudhisawasdi
Vajarabhongsa
V
D000483:Alleles; D000818:Animals; D001650:Bile Duct Neoplasms / Q000209:etiology / Q000235:genetics* / Q000469:parasitology*; D001653:Bile Ducts, Intrahepatic / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics; D018281:Cholangiocarcinoma / Q000209:etiology / Q000235:genetics* / Q000469:parasitology*; D002874:Chromosome Mapping; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005210:Fasciola hepatica / Q000472:pathogenicity; D005211:Fascioliasis / Q000150:complications / Q000473:pathology; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D010455:Peptides / Q000235:genetics*; D011379:Prognosis; D000071164:Trefoil Factor-2
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D010455:Peptides; C000604007:TFF2 protein, human; D000071164:Trefoil Factor-2