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<p>Abstract</p> <p>Background</p> <p>CpG island methylator phenotype (CIMP), in which multiple genes concordantly methylated, has been demonstrated to be associated with progression, recurrence, as well as overall survival in some types of cancer.</p> <p>Methods</p> <p>We examined the promoter methylation status of seven genes including <it>P16, CDH1, GSTP1, DAPK, XAF1, SOCS1 </it>and <it>SYK </it>in 65 cases of HCC treated with LT by methylation-specific PCR. CIMP+ was defined as having three or more genes that are concordantly methylated. The relationship between CIMP status and clinicopathological parameters, as well as tumor recurrence was further analyzed.</p> <p>Results</p> <p>CIMP+ was more frequent in HCC with AFP > 400 ng/ml than those with AFP ≤ 400 ng/ml (<it>P </it>= 0.017). In addition, patients with CIMP+ were prone to have multiple tumor numbers than those with CIMP- (<it>P </it>= 0.007). Patients with CIMP+ tumors had significantly worse recurrence-free survival (RFS) than patients with CIMP-tumors by Kaplan-Meier estimates (<it>P </it>= 0.004). Multivariate analysis also revealed that CIMP status might be a novel independent prognostic factor of RFS for HCC patients treated with LT (HR: 3.581; 95% CI: 1.473-8.710, <it>P </it>= 0.005).</p> <p>Conclusion</p> <p>Our results suggested that CIMP could serve as a new prognostic biomarker to predict the risk of tumor recurrence in HCC after transplantation.</p>