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. 2014 Jul 23;9(7):e103021.
doi: 10.1371/journal.pone.0103021. eCollection 2014.

PIK3CA gene mutations and overexpression: implications for prognostic biomarker and therapeutic target in Chinese esophageal squamous cell carcinoma

Lin Wang  1 , Ling Shan  1 , Shaokai Zhang  2 , Jianming Ying  1 , Liyan Xue  1 , Yanling Yuan  1 , Yongqiang Xie  1 , Ning Lu  1
Affiliations

PIK3CA gene mutations and overexpression: implications for prognostic biomarker and therapeutic target in Chinese esophageal squamous cell carcinoma

Lin Wang et al. PLoS One. .

Abstract

Aims: To 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.

Methods: Direct 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.

Results: Thirty 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).

Conclusions: Our results suggest PIK3CA gene mutation and overexpression could act as biomarkers for individualized molecular targeted therapy for Chinese ESCC patients.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Mutational analysis of PIK3CA exons 9 and 20 in ESCC.
Representative chromatograms of the four mutations detected in exon 9 of the PIK3CA gene and the corresponding wild-type region. (A) and (B) Wild-type sequence. (C) Mutant sequence E542Q (A1625G); (D) Mutant sequence E545A (A1634C); (E) Mutant sequence E545Q (G1633A); (F) Mutant sequence E545K (G1633C). The arrows indicate the location of the somatic mutations.
Figure 2
Figure 2. PIK3CA expression in ESCC.
Representative immunohistochemistry images of PIK3CA expression across multiple tumor grades. PIK3CA protein was localized on the cytoplasm of tumor cells. Tumors were scored on a scale from grade 0 to 3+. (A) grade 0, 100×; (B) grade 0, 200×; (C) grade 1+, 100×; (D) grade 1+, 200×; (E) grade 2+, 100×; (F) grade 2+, 200×; (G) grade 3+, 100×; (H) grade 3+, 200×; (I) normal mucosa, 100×; and (J) normal mucosa, 200×.
Figure 3
Figure 3. Kaplan-Meier curves for overall survival in ESCC.
(A) Overall survival according to PIK3CA mutation status (P = 0.251). (B) Overall survival according to PIK3CA expression status (P = 0.054).
See this image and copyright information in PMC

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This study was supported by the grant from the National Natural Science Foundation of China (#81272308). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.