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CpG Island Methylator Phenotype Associated with Tumor Recurrence in Tumor–Node–Metastasis Stage I Hepatocellular Carcinoma

  • Translational Research and Biomarkers
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Abstract

Background

CpG island methylator phenotype (CIMP), characterized by simultaneous methylation of multiple tumor suppressor genes (TSGs), has been reported to be associated with biological malignancy in many cancers. Whether CIMP is potentially predictive of clinical outcome in hepatocellular carcinoma (HCC) remains unknown.

Methods

We investigated the methylation status of ten TSGs and CIMP in 115 samples of HCC and 48 samples of corresponding nonneoplastic liver tissues using a methylation-specific polymerase chain reaction.

Results

The methylation frequencies of the ten genes examined in HCC were 40.0% for p14 ARF, 60.9% for p15 INK4b, 70.4% for p16 INK4a, 34.8% for p73, 70.4% for GSTP1, 64.3% for MGMT, 13.0% for hMLH1, 59.1% for RARβ, 82.6% for SOCS-1, and 80.9% for OPCML. CIMP+ (with six or more methylated genes) was detected in 68 (59.1%) of 115 HCCs and none of 48 nonneoplastic liver tissues. On stratified univariate analysis, patients with tumor–node–metastasis (TNM) stage I HCC with CIMP+ had significantly shorter overall survival (OS) (P = 0.002) and recurrence-free survival (RFS) (P = 0.042) than those with CIMP−. Furthermore, multivariate analysis revealed CIMP+ as an independent prognostic factor for both OS [hazard ratio (HR), 12.266; P = 0.015] and RFS (HR, 2.275; P = 0.032) in TNM stage I patients.

Conclusions

CIMP+ may specifically define a subgroup of patients with unfavorable outcome in TNM stage I HCC. Examination of CIMP status may be useful for stratifying prognosis of patients with early-stage HCC and identifying patients who are at higher risk for recurrence.

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Acknowledgment

This work was supported by the grant of China Medical Board of New York, Inc. (98-677) and the National Natural Science Foundation of China (30872489 and 30972916). The authors declare that there are no conflicts of interest or financial disclosures.

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Authors and Affiliations

  1. State Key Laboratory of Oncology in South China/Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China

    Binkui Li MD, Wenji Liu MD, Li Wang MD, Meixiang Li MD, Liang Huang MD, Pinzhu Huang MD & Yunfei Yuan MD

  2. Department of Radiation Oncology, Chenzhou No.1 People’s Hospital, Chenzhou, Hunan, China

    Wenji Liu MD

  3. Department of Clinical Oncology, Shenzhen No.2 People’s Hospital, Shenzhen, Guangdong, China

    Meixiang Li MD

  4. Department of Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China

    Jianping Wang MD, PhD

  5. Department of Surgery, The Second Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China

    Liang Huang MD

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  1. Binkui Li MD
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  2. Wenji Liu MD
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  3. Li Wang MD
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Correspondence to Yunfei Yuan MD.

Additional information

Binkui Li and Wenji Liu contributed equally to this work.

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Li, B., Liu, W., Wang, L. et al. CpG Island Methylator Phenotype Associated with Tumor Recurrence in Tumor–Node–Metastasis Stage I Hepatocellular Carcinoma. Ann Surg Oncol 17, 1917–1926 (2010). https://doi.org/10.1245/s10434-010-0921-7

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  • DOI: https://doi.org/10.1245/s10434-010-0921-7

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