PIK3CA mutation and methylation influences the outcome of colorectal cancer

Iida,Satoru; Kato,Shunsuke; Ishiguro,Megumi; Matsuyama,Takatoshi; Ishikawa,Toshiaki; Kobayashi,Hirotoshi; Higuchi,Tetsuro; Uetake,Hiroyuki; Enomoto,Masayuki; Sugihara,Kenichi

doi:10.3892/ol.2011.544

PIK3CA mutation and methylation influences the outcome of colorectal cancer

Authors:
- Satoru Iida
- Shunsuke Kato
- Megumi Ishiguro
- Takatoshi Matsuyama
- Toshiaki Ishikawa
- Hirotoshi Kobayashi
- Tetsuro Higuchi
- Hiroyuki Uetake
- Masayuki Enomoto
- Kenichi Sugihara
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Affiliations: Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, 113-8519, Japan, Graduate Education Program for Cancer Treatment Specialists, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, 113-8519, Japan, Department of Translational Oncology, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, 113-8519, Japan, Minimally Invasive Surgery Center, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, 113-8519, Japan
Published online on: December 29, 2011 https://doi.org/10.3892/ol.2011.544
Pages: 565-570

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Abstract

Colorectal cancer (CRC) occurs through the accumulation of genetic and epigenetic alterations. The epigenetic abnormalities, in cooperation with genetic alterations, are capable of causing aberrant gene function that results in cancer. In the present study, we examined mutations and methylation status in 164 CRCs to determine whether the combination of genetic and epigenetic alterations may be used to classify CRC patients in relation to their clinicopathological characteristics and outcomes. Mutation analyses for the KRAS and PIK3CA genes were performed using direct sequencing, and the MethyLight method was used to determine the methylation status of BNIP3, p16 and hMLH1. The combination of the KRAS mutation with methylation status did not have any association with clinicopathological characteristics and outcomes. However, patients with the PIK3CA mutation and/or high methylation (2 or 3 methylated genes) had significantly poorer outcomes in disease-specific survival (DSS) compared with those with wild-type PIK3CA and 0 or 1 methylated genes (P=0.0059). Additionally, multivariate analysis revealed that the PIK3CA mutation and/or a high level of methylation predicts a poor DSS independently of clinicopathological characteristics. Our results suggest that a combination of genetic and epigenetic alterations is a potent biomarker for predicting the prognosis of CRC.

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