Abstract 4769: CHFR methylation is an independent prognostic marker of poor prognosis in gastric cancer
Authors: Sugimoto Kiichi , Hulbert Alicia , Lu Zhihao , Chen Chen , Ito Tomoaki , Komiyama Hiromitsu , Kojima Yutaka , Goto Michitoshi , Tomiki Yuichi , Orita Hajime , Sakamoto Kazuhiro , Sato Koichi , Brock Malcolm V. 
Published: August 2015

Introduction : Although primary gastric cancer (PGC) is the leading cause of cancer-related death in Asia, remnant gastric cancer (RGC), a cancer deloping after a subtotal gastrectomy in the part of the stomach not excised, is rare but equally lethal. In PGC, aberrant gene methylation has been reported to be correlated with carcinogenesis and development. However, few reports describe the process of molecular carcinogenesis in RGC. CHFR is a mitotic checkpoint- and tumor suppressor gene in a diverse number of solid malignancies. CHFR is most frequently inactivated by promoter CpG island methylation and has shown to be a marker of poor prognosis and increased sensitivity to treatment with taxanes. We hypothesized that the mathylation status in CHFR could be correlated with clinicopathological factors and prognosis in RGC. We retrospectively investigated the methylation status in RGC and the correlation between the methylation status, clinicopathological factors and prognosis.

Methods : Sixty nine PGC patients and 22 RGC patients who underwent curative surgery were enrolled in the present study. We investigated the mathylation status of CHFR using quantitative methylation specific PCR. Using ROC curve, we defined a methylation rate of ≥ 5.5% as high group.

Results : There was no significant difference in CHFR methylation rate between PGC and RGC lesions (P = 0.72). There were 17 PGC patients (24.6%) and 5 RGC patients (22.7%) with the CHFR methylation high group (P = 1.00). There was a trend towards a higher proportion of undifferentiated histology and higher clinical stage in the CHFR methylation high group, compared with the low group. On multivariate analyses, the CHFR methylation high group was found to be a significant independent prognostic factor (Hazard ratio = 3.39, 95% CI 1.14-10.11, P = 0.03).

Conclusion : CHFR methylation rate was not significantly different between primary and remnant gastric cancers. But, CHFR methylation rate may be a significant independent prognostic factor in patients with gastric cancer.

Univariate and multivariate analyses according to the clinicopathological factorsClinicopathological factorsVariablesUnivariate analysisMaltivariate analysisP-valueHazard ratio95%CIP-valueAge≥ 700.63GenderMale0.30TypeRemnant0.85DifferentiationUndifferentiated0.38Invasion depthT40.0042.350.66 - 9.420.19LN metastasisN(+)0.0083.460.76 - 19.290.10StageIII0.0020.920.18 - 4.620.92CHFR methylation rateHigh group0.0083.391.14 - 10.110.03

Citation Format: Kiichi Sugimoto, Alicia Hulbert, Zhihao Lu, Chen Chen, Tomoaki Ito, Hiromitsu Komiyama, Yutaka Kojima, Michitoshi Goto, Yuichi Tomiki, Hajime Orita, Kazuhiro Sakamoto, Koichi Sato, Malcolm V. Brock. CHFR methylation is an independent prognostic marker of poor prognosis in gastric cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4769. doi:10.1158/1538-7445.AM2015-4769