PloS one · 2014
PIK3CA gene mutations and overexpression: implications for prognostic biomarker and therapeutic target in Chinese esophageal squamous cell carcinoma.
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Wang Lin, Shan Ling, Zhang Shaokai, Ying Jianming, Xue Liyan, Yuan Yanling, Xie Yongqiang, Lu Ning
Аннотация
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.
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.
Предметные рубрики MeSH
AdultAgedAged, 80 and overBiomarkers, TumorCarcinoma, Squamous CellChinaClass I Phosphatidylinositol 3-KinasesEsophageal NeoplasmsEsophageal Squamous Cell CarcinomaEsophagusExonsFemaleGene Expression Regulation, NeoplasticHumansMaleMiddle AgedPhosphatidylinositol 3-KinasesPoint MutationPrognosisSurvival Analysis