Peng Li1, Shuyu Che2, Yingxue Qi3,4,5, Ningning Luo3,4,5, Qiuju Lin6, Xiaofeng Zhu3,4,5, Yunpeng Xuan1, Mengmeng Li3,4,5, Jinlong Li1, Minghui Ge3,4,5, Tingting Sun3,4,5, Chuang Qi3,4,5, Yongjie Wang7. 1. Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, No. 59, Haier Road, Laoshan District, Qingdao, 266000, China. 2. Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China. 3. The Medical Department, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing, China. 4. Nanjing Simcere Medical Laboratory Science Co., Ltd., Nanjing, China. 5. The State Key Laboratory of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing, China. 6. Department of Oncology, Qingdao Central Medical Group, Qingdao, China. 7. Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, No. 59, Haier Road, Laoshan District, Qingdao, 266000, China. wangyongjie@qduhospital.cn.
Abstract
BACKGROUND: The incidence of lung cancer tends to be younger, and adenocarcinoma is the main histological type. Even patients with the same tumor type may have significant differences in clinical features, tumor microenvironment and genomic background at different ages. Immune checkpoint inhibitors (ICIs) have been shown to improve clinical outcomes in patients with lung adenocarcinoma (LUAD). However, differences in ICI efficacy between older and younger patients are unknown. Our study aimed to explore the relationship between age and immunotherapy in LUAD. METHODS: In our study, 1313 resected LUAD patients in our hospital were divided into young (age ≤ 50) and old groups (age > 50), and the clinical characteristic differences between them were analyzed. Of these, next-generation sequencing (NGS) was performed on the 311 cases. In addition, immune-related signatures of 508 LUAD patients were analyzed by TCGA RNA expression data. Then, we validated genomic and clinical information of 270 LUAD samples in the MSKCC cohort. RESULTS: ERBB2 and EGFR gene mutations were significantly different between the two groups, and the gene mutation number in the old group was significantly higher than that in the young group. In addition, immune-related signatures of LUAD patients were analyzed by TCGA RNA expression data, which indicated that the patients in the old group might have a better immune microenvironment. Then, we validated the MSKCC cohort and found that the TMB of the old group was significantly higher than that of the young group, and the OS of immunotherapy was longer in the old group. CONCLUSION: Our study was the first to analyze the differences in the genomic landscape and immune-related biomarkers between the young and old groups of LUAD patients and found that the old group had a better efficacy of immunotherapy, providing a reference for the study design and treatment of patients with LUAD.
BACKGROUND: The incidence of lung cancer tends to be younger, and adenocarcinoma is the main histological type. Even patients with the same tumor type may have significant differences in clinical features, tumor microenvironment and genomic background at different ages. Immune checkpoint inhibitors (ICIs) have been shown to improve clinical outcomes in patients with lung adenocarcinoma (LUAD). However, differences in ICI efficacy between older and younger patients are unknown. Our study aimed to explore the relationship between age and immunotherapy in LUAD. METHODS: In our study, 1313 resected LUAD patients in our hospital were divided into young (age ≤ 50) and old groups (age > 50), and the clinical characteristic differences between them were analyzed. Of these, next-generation sequencing (NGS) was performed on the 311 cases. In addition, immune-related signatures of 508 LUAD patients were analyzed by TCGA RNA expression data. Then, we validated genomic and clinical information of 270 LUAD samples in the MSKCC cohort. RESULTS: ERBB2 and EGFR gene mutations were significantly different between the two groups, and the gene mutation number in the old group was significantly higher than that in the young group. In addition, immune-related signatures of LUAD patients were analyzed by TCGA RNA expression data, which indicated that the patients in the old group might have a better immune microenvironment. Then, we validated the MSKCC cohort and found that the TMB of the old group was significantly higher than that of the young group, and the OS of immunotherapy was longer in the old group. CONCLUSION: Our study was the first to analyze the differences in the genomic landscape and immune-related biomarkers between the young and old groups of LUAD patients and found that the old group had a better efficacy of immunotherapy, providing a reference for the study design and treatment of patients with LUAD.
Authors: David P Carbone; Martin Reck; Luis Paz-Ares; Benjamin Creelan; Leora Horn; Martin Steins; Enriqueta Felip; Michel M van den Heuvel; Tudor-Eliade Ciuleanu; Firas Badin; Neal Ready; T Jeroen N Hiltermann; Suresh Nair; Rosalyn Juergens; Solange Peters; Elisa Minenza; John M Wrangle; Delvys Rodriguez-Abreu; Hossein Borghaei; George R Blumenschein; Liza C Villaruz; Libor Havel; Jana Krejci; Jesus Corral Jaime; Han Chang; William J Geese; Prabhu Bhagavatheeswaran; Allen C Chen; Mark A Socinski Journal: N Engl J Med Date: 2017-06-22 Impact factor: 91.245
Authors: Brian N Arnold; Daniel C Thomas; Joshua E Rosen; Michelle C Salazar; Justin D Blasberg; Daniel J Boffa; Frank C Detterbeck; Anthony W Kim Journal: J Thorac Oncol Date: 2016-04-19 Impact factor: 15.609
Authors: Reinhard Büttner; John R Gosney; Birgit Guldhammer Skov; Julien Adam; Noriko Motoi; Kenneth J Bloom; Manfred Dietel; John W Longshore; Fernando López-Ríos; Frédérique Penault-Llorca; Giuseppe Viale; Andrew C Wotherspoon; Keith M Kerr; Ming-Sound Tsao Journal: J Clin Oncol Date: 2017-10-20 Impact factor: 44.544