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EGFR-mutant lung adenocarcinoma harboring co-mutational tumor suppressor genes predicts poor prognosis

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Introduction

EGFR mutations occur most frequently in patients with lung adenocarcinoma in East Asia. However, the prognostic and therapeutic impact of co-mutational status of EGFR and tumor suppressor genes is not fully understood. This study aims to provide a deeper understanding of lung adenocarcinoma patients with co-mutation of EGFR and tumor suppressor genes.

Methods

From November 2009 to May 2016, 675 patients with lung adenocarcinoma who underwent complete surgery were included in this study. Samples were collected and pathologically examined. Whole-exome sequencing was performed on 197 samples, while direct sequencing of major driver genes, including EGFR, KRAS, ERBB2 and BRAF and Ion-torrent targeted sequencing of tumor suppressor genes, including TP53, KEAP1, MGA, NF1, RB1, SMARCA4 and STK11, were performed on 478 samples. Tumor mutational burden was calculated and survival analyses were performed.

Results

The frequency of EGFR and TP53 mutation was 409 (60.6%) and 215 (31.9%), respectively. Co-mutation of EGFR and TP53 occured in 151 patients (22.4%), while co-mutation of EGFR and at least one tumor suppressor gene occured in 184 patients (27.3%). Compared with patients with only EGFR mutations, patients with co-mutations of EGFR and TP53 had a higher tumor mutational burden (p = 0.007) and worse recurrence-free survival (p = 0.010), while patients with co-mutations of EGFR and at least one tumor suppressor gene had a higher tumor mutational burden (p = 0.007), worse recurrence-free survival (p = 0.016) and worse overall survival (p = 0.018).

Conclusions

Lung adenocarcinoma patients harboring EGFR and co-mutational tumor suppressor genes should be regarded as a unique subgroup.

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Funding

This work was supported by the National Natural Science Foundation of China (Grant numbers: 81572253 and 81930073); Shanghai Shen Kang Hospital Development Center City Hospital Emerging Cutting-edge Technology Joint Research Project (Grant number: SHDC12017102); Shanghai Municipal Health Commission Key Discipline Project (Grant numbers: 2017ZZ02025 and 2017ZZ01019).

Author information

Author notes

  1. Yue Zhao, Yunjian Pan and Chao Cheng contributed equally to this work and are considered co-first authors.

Authors and Affiliations

  1. Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China

    Yue Zhao, Yunjian Pan, Chao Cheng, Difan Zheng, Yang Zhang, Zhendong Gao, Fangqiu Fu, Hang Li, Shanbo Zheng, Lingdun Zhuge, Hengyu Mao, Muyu Kuang, Xiaoting Tao, Yizhou Peng, Hong Hu, Jiaqing Xiang, Yihua Sun & Haiquan Chen

  2. Institute of Thoracic Oncology, Fudan University, Shanghai, 200032, China

    Yue Zhao, Yunjian Pan, Chao Cheng, Difan Zheng, Yang Zhang, Zhendong Gao, Fangqiu Fu, Hang Li, Shanbo Zheng, Lingdun Zhuge, Hengyu Mao, Muyu Kuang, Xiaoting Tao, Yizhou Peng, Hong Hu, Jiaqing Xiang, Yihua Sun & Haiquan Chen

  3. State Key Laboratory of Engineering, School of Life Sciences, Fudan University, Shanghai, 200433, China

    Yue Zhao, Yunjian Pan, Chao Cheng, Difan Zheng, Yang Zhang, Zhendong Gao, Fangqiu Fu, Hang Li, Shanbo Zheng, Lingdun Zhuge, Hengyu Mao, Muyu Kuang, Xiaoting Tao, Yizhou Peng, Hong Hu, Jiaqing Xiang, Yihua Sun & Haiquan Chen

  4. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    Yue Zhao, Yunjian Pan, Chao Cheng, Difan Zheng, Yang Zhang, Zhendong Gao, Fangqiu Fu, Hang Li, Shanbo Zheng, Lingdun Zhuge, Hengyu Mao, Muyu Kuang, Xiaoting Tao, Yizhou Peng, Hong Hu, Jiaqing Xiang, Yuan Li, Yihua Sun & Haiquan Chen

  5. Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China

    Yuan Li

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  1. Yue Zhao
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  2. Yunjian Pan
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Corresponding author

Correspondence to Haiquan Chen.

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These authors declare no conflicts of interest.

Ethical approval

This study was approved by the Committee for Ethical Review of Research (Fudan University Shanghai Cancer Center IRB# 090977-1).

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Supplementary file1 (DOCX 13 kb)

432_2020_3237_MOESM2_ESM.jpg

Supplementary figure 1. Pie charts showing the co-mutational composition of each driver gene with every tumor suppressor gene in lung adenocarcinoma. Composition of each driver gene is shown in patients with mutations in a) at least one tumor suppressor gene, b) TP53, c) MGA, d) NF1, e) RB1, f) SMARCA4, g) STK11 and h) KEAP1. (JPG 2108 kb)

Supplementary file3 (DOCX 12 kb)

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Zhao, Y., Pan, Y., Cheng, C. et al. EGFR-mutant lung adenocarcinoma harboring co-mutational tumor suppressor genes predicts poor prognosis. J Cancer Res Clin Oncol 146, 1781–1789 (2020). https://doi.org/10.1007/s00432-020-03237-3

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  • DOI: https://doi.org/10.1007/s00432-020-03237-3

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