Association between CHFR methylation and chemosensitivity of paclitaxel in advanced gastric cancer

Abstract

Aberrant methylation of CHFR (Checkpoint with forkhead associated and ring finger) gene was frequently happened in cancer and had been reported to be associated with the sensitivity of microtubule inhibitors in several cancer cells containing gastric cancer cells in vitro experiments [1]. However, the clinical significance of CHFR methylation and chemosensitivity of microtubule inhibitors (paclitaxel or docetaxel) in gastric cancer patients was investigated only in few studies with limited samples, and the conclusion was controversial [2, 3]. In this study, we aimed to investigate the association between CHFR methylation and the sensitivity of paclitaxel in Chinese advanced gastric cancer (AGC) patients to identify the potential predictor of paclitaxel. Tumor or matched non-tumor biopsies prior chemotherapy from 117 AGC patients receiving paclitaxel plus capecitabine (cohort 1, n = 59) or cisplatin plus capecitabine (cohort 2, n = 58) were retrospectively collected and analyzed for CHFR methylation status by MethyLight assay. We further investigated the association between CHFR methylation and the sensitivity of paclitaxel in AGC patients to identify its predictive significance. This study was approved by the Ethics Committee of Peking University Cancer Hospital and was performed according to the Declaration of Helsinki Principles. The median age of patients was 59 years with all patients had been evaluable for clinical response. The percentage of responders and non-responders was 36.8 and 63.2 %, respectively. Among all 117 patients, 46 patients had tumor tissues and matched non-tumor tissues. CHFR methylation occurred frequently in gastric cancer tissues (35/117, 29.9 %) compared to nontumor tissues (0/46, 0 %; P\ 0.001). For all patients, no significant differences were found between CHFR methylation and age, gender, histological differentiation, Lauren classification, metastasis, or HER2 status (all P[ 0.05). We analyzed the correlation between CHFR methylation and chemosensitivity of paclitaxel in clinical cohorts. However, no significant differences were seen between CHFR methylation and clinical response in all patients or any clinical cohort (P[ 0.05) as shown in Table 1. Up to August 2013, the median PFS and OS for all patients were 143 and 288 days, respectively. There were no differences of PFS or OS between patients with positive and negative methylation of CHFR in all patients (Table 1). For cohort 1, the median PFS and OS in patients with positive methylation of CHFR were 165 and 283 days, which had no difference with those (154 and 335 days) in patients with negative methylation of CHFR (Table 1). Also, the same results were seen in cohort 2 (Table 1). This study demonstrated that CHFR methylation was frequent and specific in gastric cancer tissues, while absent in non-tumor tissues. Our results verified that no correlation was found between CHFR methylation and paclitaxel chemosensitivity in clinical cohorts, which helped to disabuse the inconclusive results. The correlation between CHFR methylation and prognosis of patients needed to be further validated in large samples. M. Wang L. Shen (&) Department of GI Oncology, Peking University Cancer Hospital and Institute, No. 52, Fucheng Road, Haidian District, Beijing 100142, China e-mail: lin100@medmail.com.cn