High polymerase ε expression associated with increased CD8+T cells improves survival in patients with non-small cell lung cancer

被引:5
|
作者
Min, Kyueng-Whan [1 ]
Kim, Wan-Seop [2 ]
Kim, Dong-Hoon [3 ]
Son, Byoung Kwan [4 ]
Oh, Young Ha [1 ]
Kwon, Mi Jung [5 ]
Lee, Hye Seung [2 ]
Lee, Seung Eun [2 ]
Kim, In Ae [6 ]
Moon, Ji-Yong [7 ]
Kim, Kyoung-Yeon [8 ]
Park, Jung-Hoon [8 ]
机构
[1] Hanyang Univ, Coll Med, Guri Hosp, Dept Pathol, Guri, Gyeonggi Do, South Korea
[2] Konkuk Univ, Sch Med, Med Ctr, Dept Pathol, Seoul, South Korea
[3] Sungkyunkwan Univ, Sch Med, Kangbuk Samsung Hosp, Dept Pathol, Seoul, South Korea
[4] Eulji Univ, Sch Med, Eulji Hosp, Dept Internal Med, Seoul, South Korea
[5] Hallym Univ, Coll Med, Sacred Heart Hosp, Dept Pathol, Anyang, Gyeonggi Do, South Korea
[6] Konkuk Univ, Med Ctr, Sch Med, Dept Internal Med, Seoul, South Korea
[7] Hanyang Univ, Coll Med, Guri Hosp, Dept Internal Med, Guri, Gyeonggi Do, South Korea
[8] Macrogen Inc, Seoul, South Korea
来源
PLOS ONE | 2020年 / 15卷 / 05期
关键词
MUTATIONS; PATHWAY; RECOMMENDATIONS; SENSITIVITY; DASATINIB; LANDSCAPE; PATTERNS; PD-1;
D O I
10.1371/journal.pone.0233066
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
DNA replicase polymerase epsilon (POLE) is critical in proofreading and correcting errors of DNA replication. Low POLE expression plays a pivotal role in accumulation of mutations and onset of cancer, contributing to development and growth of tumor cells. The aim of this study is to reveal the survival, alternative genes and antitumoral immune activities in non-small cell lung cancer (NSCLC) patients with low POLE expression and provide treatment strategies that can increase their survival rates. This study investigated the clinicopathologic parameters, various tumor-infiltrating lymphocytes (TILs), endogenous retrovirus, molecular interactions and in vitro drug screen according to POLE mutation/expression in 168 and 1,019 NSCLC patients from the Konkuk University Medical Center (KUMC) and the Cancer Genome Atlas, respectively. We identified mutations of 75 genes in the sequencing panels, with POLE frame shift p.V1446fs being the most frequent (56.8%) in KUMC based on 170 targeted sequencing panels. Mutant and high expression of POLE correlated with favorable prognosis with increased TILs and tumor mutation burden, compared with wild type and low expression of POLE. We found specific molecular interactions associated with cell cycle and antigen presentation. An in vitro drug screen identified dasatinib that inhibited growth of the NSCLC cell line with low POLE expression. POLE could contribute to the future development of anticancer drugs for patients with NSCLC.
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页数:12
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