Combination of haptoglobin and osteopontin could predict colorectal cancer hepatic metastasis.
OBJECTIVE
This study aimed to identify novel molecular markers for the early detection of colorectal cancer liver metastasis.


METHODS
Genes related to hepatic metastasis were screened from the Oncomine database. The candidate markers were tested by immunohistochemistry, and their predictive accuracy was assessed by the cross-validation method and an independent test set.


RESULTS
We got three datasets containing 2,973 genes that were highly expressed in primary colon cancer tissues compared with non-metastatic colon cancer tissues and identified 7 candidate molecules for immunohistochemical validation. A total of 213 colorectal cancer samples were randomly divided into a training set (113 cases) and a blind testing set (100 cases). In the training set, immunohistochemical analysis showed that HP, OPN, and PTGIS expression were significantly higher in the hepatic metastasis group than in the non-metastasis group. Logistic regression analysis showed that HP and OPN levels in primary tumors and lymph node metastasis status were the only significant (P<0.05) parameters for detecting liver metastasis. The predictive accuracy of markers was assessed by the cross-validation method and an independent test set. In leave-one-out cross-validation, the two markers combined with clinicopathologic features resulted in 91.2% sensitivity and 96.4% specificity for hepatic metastasis detection. In an independent test set, the combination achieved 94.5% sensitivity and 88.9% specificity for predicting the hepatic metastasis of colorectal cancer.


CONCLUSIONS
Our results suggest that combined HP and OPN expression levels are significantly related to liver metastasis and prognosis, and, if this is validated, they could be used as accurate predictors of liver metastasis in colorectal cancer.
State Key Laboratory of Molecular Oncology, Cancer Institute Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China. sunlichao_1980@hotmail.com
Lichao
L
Sun
Jian
J
Pan
Liang
L
Peng
Lv
L
Fang
Xuan
X
Zhao
Lixin
L
Sun
Zhihua
Z
Yang
Yuliang
Y
Ran
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D006242:Haptoglobins / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D053495:Osteopontin / Q000378:metabolism*; D011379:Prognosis; D015996:Survival Rate; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D006242:Haptoglobins; D053495:Osteopontin; D003577:Cytochrome P-450 Enzyme System; C472456:PTGIS protein, human