cDNA array analysis for prediction of hepatic metastasis of colorectal carcinoma.

PURPOSE

Distant metastasis is a significant prognostic factor of colon carcinoma. Adjuvant chemotherapy has been shown to decrease its recurrence. However, there are no definitive methods for the diagnosis of hepatic recurrence after potentially curative surgery. The aim of this study was to evaluate the accuracy of mRNA expression profiling using samples obtained from primary tumors to predict hepatic recurrence.

METHODS

Patients with stage III colorectal carcinoma without any recurrence for at least 5 years (group A: n = 9) and patients with stage IV carcinoma with hepatic metastasis (group B: n = 10) were included in this study. Tissue samples were collected from the primary tumor and adjacent normal colonic mucosa at the time of surgery in each patient. Total RNA was extracted and the mRNA expression profile was examined using a cDNA macroarray.

RESULTS

A hierarchical clustering analysis revealed a dendrogram in which the patients were divided into two clusters. One cluster consisted of seven patients in group A and two in group B. The other consisted of two patients in group A and eight in group B. Therefore, the positive and negative predictive value of hierarchical clustering analysis for hepatic metastasis was 80.0% and 78.8%, respectively. Fifteen genes were revealed to be upregulated and 12 were downregulated in group B. The upregulated genes included CCNA2, TP53, and MDM2, while the downregulated genes included CDH1, GADD45A, and BCL2L2.

CONCLUSIONS

mRNA expression profiling by a cDNA array analysis of specimens obtained from primary tumors was found to be useful for distinguishing patients with and without hepatic metastasis. This method is expected to contribute to the identification of patients at high risk for hepatic recurrence, while also helping in the administration of intensive adjuvant chemotherapy for such high risk patients.