A single-nucleotide polymorphism involved in alternative splicing of PTEN is associated with chemotherapy resistance in breast cancer in Chinese population

Author:

Wang Jing1,Zhang Shasha1,Zhang Zhongliang2,Ma Qinglong1,Chen Xiaohua3,Zhao Dapeng3,Zhao Meie1,Wang Chunwei4,Di Cuixia3,xie xiaodong1

Affiliation:

1. Lanzhou University

2. First People's Hospital of Lanzhou City

3. Chinese Academy of Sciences

4. Gansu Provincial Hospital

Abstract

Abstract Background Chemoresistance is still the main reason for the failure of breast cancer treatment and is the main cause of death of breast cancer patients. Although many studies have shown the association between genetic polymorphisms of PTEN and chemotherapy resistance, the molecular mechanism of breast cancer chemotherapy has not been further studied. This study aims to investigate the potential association between PTEN gene polymorphism and breast chemotherapy resistance in the Chinese population, and explore whether alternative splicing of the PTEN gene is affected by the gene polymorphism. Methods The study included 234 patients with breast cancer chemotherapy, 157 chemotherapy sensitive cases and 77 chemotherapy resistant cases. rs786204926 of the PTEN gene was analysed by Sanger sequence and Sequenom MassArray typing technology. Furthermore, we used silicon analysis to predict whether polymorphism affect the process of alternative splicing and to analyze how it affects. Results In genotyping and allelic analysis, there was a significant association between rs786204926 polymorphism and breast cancer chemotherapy resistance. Carrying the G allele or AG genotype will reduce the risk of breast cancer-based resistance to chemotherapy with anthracyclines. Silicon analysis showed that the mutation of rs786204926 produced a new receptor site, which might affect alternative splicing of PTEN gene. Conclusions We speculate that the mechanism of breast cancer chemotherapy resistance might be caused by a change in the alternative splicing caused by the rs786204926 of the PTEN gene. Thus, our study might provide theoretical guidance for the individualized treatment of clinical breast cancer patients.

Publisher

Research Square Platform LLC

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