5740

PTGIS

prostaglandin I2 (prostacyclin) synthase;PTGIS;prostaglandin I2 (prostacyclin) synthase

cytochrome P450, family 8, subfamily A, polypeptide 1|prostacyclin synthase|prostaglandin I2 synthase

20q13.13

protein-coding

The purpose of this study was to evaluate the predictive ability of PTGIS for liver metastasis. Protein expression of PTGIS was analyzed on tissue microarray consisting of 117 CRC cases with liver metastasis (M1) and 104 cases of CRC without liver metastasis at least 5 years after resection of primary CRC (M0) by immunohistochemistry. expression of PTGIS in 147 of 221 of primary lesions exhibited positive staining. Moreover, the PTGIS expression was significantly higher in CRC-M1 than CRC-M0 group. More importantly, the 87% (20/23) heterochronous metastatic cases showed positive staining for PTGIS. Collecting the primary and liver metastatic tumor samples from the same colon cancer patients, we tested the expression of PTGIS and revealed that the expression level of PTGIS in the hepatic metastases was noticeably higher than in the matched primary colon cancer tissues from the same patient in 9 out of 16 cases examined. Logistic regression analysis indicated that the expression of PTGIS and lymph node involvement were risk factors in colon cancer liver metastasis independent of the other variables. In leave-one-out validation model, the combination of PTGIS and lymph node involvement yielded the 89.7% satisfactory sensitivity and 83% specificity for detection of hepatic metastasis. Kaplan-Meier survival analysis revealed a correlation between higher PTGIS expression levels and shorter overall survival times. In conclusion, our results suggest that PTGIS combined with lymph node involvement may be used as accurate predictors of liver metastasis in colorectal cancer.

PURPOSE: 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.