PIK3CA Gene Mutations and Overexpression: Implications for Prognostic Biomarker and Therapeutic Target in Chinese Esophageal Squamous Cell Carcinoma

Lin Wang,Liyan Xue,Jianming Ying,Yanling Yuan,Ling Shan,Shaokai Zhang,Ning Lu,Yongqiang Xie,Hiromu Suzuki

doi:10.1371/journal.pone.0103021

Abstract

AimsTo evaluate PIK3CA gene mutations and PIK3CA expression status in Chinese esophageal squamous cell carcinoma (ESCC) patients, and their correlation with clinicopathological characteristics and clinical outcomes.MethodsDirect sequencing was applied to investigate mutations in exons 9 and 20 of PIK3CA in 406 Chinese ESCC patients. PIK3CA expression was evaluated using immunohistochemistry analysis. The associations of PIK3CA gene mutations and PIK3CA expression with clinicopathological characteristics and clinical outcome were examined.ResultsThirty somatic point mutations (30/406, 7.4%) were identified in exon 9 whereas no mutations were detected in exon 20. PIK3CA mutations were not correlated with clinicopathological characteristics or clinical outcomes. However in the ESCC patients with family cancer history, PIK3CA mutations were independently correlated with worse overall survival (multivariate hazard ratio (HR) = 10.493, 95% CI: 2.432–45.267, P = 0.002). Compared to normal esophageal tissue, PIK3CA was significantly overexpressed in cancer tissue (P<0.001). PIK3CA overexpression was independently associated with higher risk of local recurrence (multivariate HR = 1.435, 95% CI: 1.040–1.979, P = 0.028). In female ESCC patients, PIK3CA overexpression was independently correlated with worse overall survival (multivariate HR = 2.341, 95% CI: 1.073–5.108, P = 0.033).ConclusionsOur results suggest PIK3CA gene mutation and overexpression could act as biomarkers for individualized molecular targeted therapy for Chinese ESCC patients.

Highlights

Esophageal squamous cell carcinoma (ESCC) is the predominant histological subtype of esophageal cancer in East Asian countries [1], accounting for more than 90% of the total esophageal cancer cases [1]
The 5-year survival rates of ESCC were between 11.1% and 56.5% depending on the clinical stage at the time of diagnosis [4]
PIK3CA mutations were not correlated with clinicopathological characteristics, including age, gender, tobacco use, alcohol use, family cancer history, tumor location, pathologic stage, differentiation, lymph node metastasis, tumor embolus, local recurrence, and prognosis

Summary

Introduction

Esophageal squamous cell carcinoma (ESCC) is the predominant histological subtype of esophageal cancer in East Asian countries [1], accounting for more than 90% of the total esophageal cancer cases [1]. Epidemiologic studies have reported that alcohol and tobacco use as well as low consumption of fruits and vegetables are risk factors of ESCC worldwide [2]. In some regions of north and central China, the incidence of ESCC exceeds 100/100,000 cases per year [3]. Despite the development of various therapeutic strategies for ESCC, including surgery, chemotherapy, radiotherapy, and combination therapy, the prognosis for ESCC patients remains unfavorable. The 5-year survival rates of ESCC were between 11.1% and 56.5% depending on the clinical stage at the time of diagnosis [4]. New therapeutic targets for ESCC treatment are urgently needed

Methods

Results

Conclusion