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
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
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
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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