Osteopontin promoter polymorphisms at locus -443 are associated with metastasis and poor prognosis of human intrahepatic cholangiocarcinoma in Chinese population.
OBJECTIVE
Osteopontin (OPN) is known to be a secreted adhesive glycoprotein. Role of OPN in human intrahepatic cholangiocarcinoma (ICC) has not been well understood. This study explored whether genetic variations in the osteopontin gene are associated with ICC risk, progression and metastasis.


METHODS
260 patients with stages I to IV between 2008 and 2013 were recruited in this study and same number healthy persons were used as control. OPN-66 T/G, -156 G/GG and -443 C/T variants were genotyped using DNA from blood lymphocytes. Chi-square test and a Fisher's exact test were used to analyze the genotype distribution between healthy subjects and patients, and further its distribution among TNM stages and incidence metastasis in patients.


RESULTS
For the variant at nt- 443 (CC), there was a significant difference between the number of patients with stage IV and those with all other stages of ICC (P < 0.01). Patients with -443 (CC) variant had significant higher incidence of lymph and distant metastasis development compared to other genotypes. For the variant at nt- 443 (CT), there was a significant difference between the number of ICC patients with stage III + IV and those with stage I + II (P < 0.01). The survival rates for ICC patients with the C/C genotype were significantly lower than for patients with the other two genotypes (C/T, T/T).


CONCLUSIONS
OPN -443 C/T polymorphism is a potential predictive marker of metastasis and poor prognosis in ICC patients.
Department of Hepatobiliary, PLA General Hospital No. 28 Fu Xing Road, Beijing 100853, China.
Xiang-Qian
XQ
Zhao
Department of Hepatobiliary, PLA General Hospital No. 28 Fu Xing Road, Beijing 100853, China.
Huan-Xian
HX
Ma
Department of Hepatobiliary, PLA General Hospital No. 28 Fu Xing Road, Beijing 100853, China.
Mao-Sheng
MS
Su
Department of Hepatobiliary, PLA General Hospital No. 28 Fu Xing Road, Beijing 100853, China.
Lei
L
He
D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic / Q000473:pathology*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000401:mortality / Q000556:secondary*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D053495:Osteopontin / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D055815:Young Adult
C506895:SPP1 protein, human; D053495:Osteopontin
Osteopontin; genetic variants; intrahepatic cholangiocarcinoma; metastasis