Loss of ARHI expression in colon cancer and its clinical significance

AIM OF THE STUDY The Ras-related tumour suppressor gene aplasia Ras homolog member I (ARHI) is downregulated in many types of cancer, including ovarian cancer and hepatocellular carcinoma. In the present study, we explore the expression level and role of ARHI in colon cancer. Moreover, the mechanisms that down-regulate expression of ARHI in colon cancer will be further investigated. MATERIAL AND METHODS ARHI expression levels were evaluated with immunohistochemistry, reverse transcriptase-PCR, and western blot. Loss of heterozygosity (LOH), single strand conformation polymorphism (SSCP), and methylation-specific PCR (MSP) were used to study the mechanisms of ARHI down-regulation. RESULTS Low expression of ARHI was observed in 61.7% (37/60) of colon cancer specimens. Compared with the paired noncancerous tissues, ARHI expression was significantly decreased in colon cancer tissues. Furthermore, low ARHI expression was significantly associated with worse differentiation degree and Dukes' stage (P < 0.05). Methylation-specific PCR assay revealed that the methylation rates of ARHI were 53.3% (16/30) and 46.7% (14/30) in ARHI CpG I and CpG II, respectively. Therefore, methylation of promoter may be involving in down regulation of ARHI expression. CONCLUSIONS These data highlight an important role for ARHI in colon cancer, which could be a therapeutic strategy against this malignancy.