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Incidence and PD-L1 Expression of MET 14 Skipping in Chinese Population: A Non-Selective NSCLC Cohort Study Using RNA-Based Sequencing

Authors Xu Z, Li H, Dong Y, Cheng P, Luo F, Fu S, Gao M, Kong L, Che N

Received 5 December 2019

Accepted for publication 17 May 2020

Published 30 June 2020 Volume 2020:13 Pages 6245—6253

DOI https://doi.org/10.2147/OTT.S241231

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Takuya Aoki


Ziguang Xu,1,* Hongxia Li,2,* Yujie Dong,3,* Peng Cheng,4 Fang Luo,4 Shijun Fu,5 Min Gao,5 Lingfei Kong,1 Nanying Che3

1Department of Pathology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Pathology, Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Novogene Co., Ltd, Beijing, People’s Republic of China; 5Medical Affairs Department, Pfizer Oncology, Shanghai, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Nanying Che
Department of Pathology, Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, No. 97 Ma Chang, Tongzhou District, Beijing 101149, People’s Republic of China
Email nany_che@126.com
Lingfei Kong
Department of Pathology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, No. 7, Weiwu Road, Zhengzhou, Henan 450003, People’s Republic of China
Email lfkong9@163.com

Background: Mesenchymal–epithelial transition (MET) exon14 skipping mutations represent a clinically unique molecular subtype of NSCLC. The prevalence rates of MET exon 14 skipping in lung adenocarcinoma (ADC) range from 0.9% to 4.0% in Asian populations. Since some somatic variants that do not encompass the MET exon 14 splice sites might also induce MET exon 14 skipping, the RNA-based sequencing is speculated as the most accurate method for detecting exon 14 skipping.
Patients and Methods: A total of 951 NSCLC patients from two hospitals were enrolled in this study. MET exon14 skipping was detected using RNA-based next-generation sequencing (NGS). Also, immunohistochemistry (IHC) was performed in 405 samples simultaneously.
Results: The overall estimated prevalence of MET exon 14 skipping was approximately 1.8% in ADCs and 1.7% in NSCLCs. The detection rate of MET exon 14 skipping from surgical resection specimen was 2.3% in NSCLCs and 2.0% in ADCs. The MET exon 14 skipping was identified in 6.6% of EGFR/KRAS/ALK/ROS1/RET-negative ADCs. Additionally, PD-L1 was found to be highly expressed in NSCLC patients harboring MET exon 14 skipping (P< 0.01).
Conclusion: The prevalence of MET exon14 skipping in lung ADCs in the East Asian population was similar to that of the Western population as assessed by RNA-based NGS. The NSCLC patients with MET exon 14 skipping were older than those with other oncogenic driver mutations, such as EGFR, ALK, and ROS1. In addition, PD-L1 was highly expressed in NSCLC patients with MET exon 14 skipping.

Keywords: non-small cell lung cancer, MET exon14 skipping, next-generation sequencing, PD-L1

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