Association of PTEN Gene SNPs rs2299939 With PFS in Patients With Small Cell Lung Cancer Treated With Early Radiotherapy.

Chunbo Wang,Xiaoqing Zhang,Yu Li,Wenyang Zhou,Lijun Yang,Yiqun Li,Depeng Yang,Huaxin Li,Huan Nie,Xiaohan Zhang,Pingping Wang

doi:10.3389/fgene.2020.00298

Abstract

Lung cancer has higher morbidity and mortality than most cancers. It is common that there are some phenomenons of secondary drug resistance, radiotherapy resistance and poor prognosis during the treatment of small cell lung cancer (SCLC). Recent studies revealed that the single-nucleotide polymorphisms (SNPs) are associated with the curative effect among patients with the same pathological type and stage. Our study analyzed the start time of radiotherapy and the relationship between PTEN gene rs2299939 polymorphisms and survival time among 116 SCLC patients. The results showed that early radiotherapy significantly improved the time of survival in patients compared with late radiotherapy (P = 0.029). Simultaneously, the study found that patients with the rs2299939 AA genotype showed significant sensitivity to both early and late radiotherapy, but early radiotherapy is better. The median survival time of CC genotype patients was 12 months in the early radiotherapy group while it was 9 months in the late radiotherapy group, thus recommending early radiotherapy among these patients. In addition, it was found that rs2299939 could regulate the expression of related genes in peripheral blood and lung tissues by eQTL analysis. This study revealed that the early radiotherapy could prolong the PFS of SCLC and shall be performed in SCLC treatment.

Highlights

Lung cancer is a type of common malignancy with high morbidity and mortality, seriously threatening human health (Torre et al, 2015)
This study analyzed the different timing of radiotherapy start among 116 patients with small cell lung cancer (SCLC) and the polymorphisms of PTEN, which is related to DNA damage repair
Radiotherapy means that radiotherapy begins after the first or second cycle of chemotherapy, while late radiotherapy begins after the third cycle of chemotherapy. van Meerbeeck regarded 90 days as the critical point of length of remission

Summary

INTRODUCTION

Lung cancer is a type of common malignancy with high morbidity and mortality, seriously threatening human health (Torre et al, 2015). PTEN is an inhibitor of the PI3K–AKT– mTOR pathway, and its inactivation leads to accelerating SCLC growth and increasing metastases in a Trp and Rb1-inactivated deleted system (Cui et al, 2014) In this DNA damage repair process, some studies have shown that functional single-nucleotide polymorphisms (SNPs) could affect the expression of DNA damage repair-related genes (Czarny et al, 2017). This study analyzed the different timing of radiotherapy start among 116 patients with SCLC and the polymorphisms of PTEN (rs2299939), which is related to DNA damage repair. The results will increase the understanding of the relation between the polymorphisms of DNA damage repair gene and SCLC, and it will provide new guidance for clinical treatment on SCLC of different genotypes

MATERIALS AND METHODS

RESULTS

DISCUSSION

ETHICS STATEMENT