Retrospective Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 7, 2018; 24(5): 631-640
Published online Feb 7, 2018. doi: 10.3748/wjg.v24.i5.631
PIK3CA and TP53 mutations predict overall survival of stage II/III colorectal cancer patients
A-Jian Li, Hua-Guang Li, Er-Jiang Tang, Wei Wu, Ying Chen, Hui-Hong Jiang, Mou-Bin Lin, Lu Yin
A-Jian Li, Lu Yin, Department of General Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
Hua-Guang Li, Er-Jiang Tang, Ying Chen, Center for Translational Medicine, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China
Wei Wu, Hui-Hong Jiang, Mou-Bin Lin, Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China
Author contributions: Li AJ, Lin MB and Yin L designed the research; Li AJ, Li HG, Chen Y and Jiang HH performed the research; Li AJ, Wu W, Tang EJ and Li HG contributed to the analysis; Lin MB, Chen Y and Yin L supervised the study; Li AJ and Li HG wrote the paper.
Supported by the National Natural Science Foundation of China, No. 81272480; and Science and Technology Commission of Shanghai Municipality, No. 15411969900 and No. 16DZ2342200.
Institutional review board statement: This study was reviewed and approved by the Yangpu Hospital Institutional Review Board.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Lu Yin, PhD, Doctor, Surgeon, Department of General Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, No. 301, Yanchang Road, Shanghai 200072, China. yindalu@tongji.edu.cn
Telephone: +86-21-66301051 Fax: +86-21-66301090
Received: November 13, 2017
Peer-review started: November 13, 2017
First decision: December 3, 2017
Revised: December 13, 2017
Accepted: December 19, 2017
Article in press: December 19, 2017
Published online: February 7, 2018
Processing time: 78 Days and 16.9 Hours
Abstract
AIM

To investigate the predictive value of PIK3CA and TP53 mutation status in colorectal cancer (CRC) patients treated with 5-fluorouracil-based chemotherapy.

METHODS

In this study, a total of 315 patients with histologically proven CRC were enrolled from Yangpu Hospital affiliated to Shanghai Tongji University between 2007 and 2011. Of these patients, 241 with stage II/III CRC received 5-fluorouracil-based adjuvant chemotherapy. Formalin-fixed paraffin-embedded lesion samples of the patients with curatively resected CRC were collected. Next-generation sequencing was performed to identify somatic gene mutations. The correlation of PIK3CA and TP53 mutation status with overall survival (OS) was analyzed using a Cox proportional hazard model and the Kaplan-Meier method.

RESULTS

Among the 241 patients with stage II/III in this cohort, the PIK3CA and/or TP53 mutation was detected in 177 patients, among which 54 patients had PIK3CA and TP53 double mutations. The PIK3CA or TP53 mutation was not significantly correlated with OS in univariate and multivariate analyses. Compared with patients without PIK3CA and TP53 mutations, those with double PIK3CA-TP53 mutations showed a significantly worse survival (univariate HR = 2.21; 95%CI: 1.15-4.24; multivariate HR = 2.02; 95%CI: 1.04-3.91). The PIK3CA mutation located in the kinase domain showed a trend toward a shorter OS compared with wild-type tumors (multivariate HR = 1.56; 95%CI: 1.00-2.44; P = 0.052). The Kaplan-Meier curve showed that patients harboring the PIK3CA mutation located in the kinase domain had a worse clinical outcome than those with wild-type status (Log-rank P = 0.041)

CONCLUSION

Double mutation of PIK3CA and TP53 is correlated with a shorter OS in stage II/III CRC patients treated with 5-fluorouracil-based therapy.

Keywords: Overall survival; Colorectal cancer; PIK3CA; TP53; 5-fluorouracil; Double mutation

Core tip: Targeted next-generation sequencing was used to detect gene mutations rather than mutational hotspots in the present study. This manuscript is by far the first to report the predictive value of the combined mutation status of PIK3CA and TP53 in colorectal cancer patients receiving 5-FU-based adjuvant chemotherapy. Our data revealed that the double mutation of PIK3CA and TP53 is an independent predictive factor for overall survival in stage II/III patients receiving 5-FU-based chemotherapy.