Open Access

Clinicopathological and molecular characteristics of patients with hypermutant lung cancer: A retrospective cohort study

  • Authors:
    • Hongbin Zhang
    • Yuan Wang
    • Qiaoxia Ji
    • Hongmei Cai
    • Xiangcun Liang
    • Jiong Xie
    • Hua Li
    • Jun Wang
    • Guiyun Zhu
    • Erpeng Tian
    • Lingling Zhu
    • Mingming Yuan
    • Rongrong Chen
    • Min Zhao
  • View Affiliations

  • Published online on: February 25, 2021     https://doi.org/10.3892/ol.2021.12590
  • Article Number: 329
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Tumor mutation burden (TMB) is an independent indicator used to select patients sensitive to immunotherapy. The present study aimed to investigate the clinicopathological and molecular characteristics of patients with hypermutant lung cancer to identify an economical, simple and complementary method for predicting TMB and immunotherapy responses. In total, 1,000 patients with lung cancer were randomly selected, and their samples were submitted to next‑generation sequencing, with their TMB status reviewed. The threshold of hypermutation was set to 17.24 mutations (muts)/Mb. The proportion of smokers was higher in the hypermutant cohort (n=67) compared with in the non‑hypermutant cohort (n=933; 85.1 vs. 46.6%; P<0.0001). Compared with in the non‑hypermutant cohort, the proportion of squamous cell carcinoma cases and small cell lung cancer cases was higher in the hypermutant cohort (22.4 vs. 13.1% and 6.0 vs. 2.6%, respectively). In addition, compared with in the non‑hypermutant cohort, mutations in the low‑density lipoprotein receptor‑related protein 1B were more frequently observed in the hypermutant cohort (67.2 vs. 14.3%; P<0.0001). A similar trend was obtained for all genes tested, except for the EGFR gene. Furthermore, in the hypermutant cohort, the prevalence of microsatellite instability was extremely high (9.0%). The mutation frequency in DNA damage response (DDR) genes was notably higher in the hypermutant cohort, where several DDR‑associated genes were enriched, compared with in the non‑hypermutant cohort. The enrichment analysis revealed a strong association between mutations in Notch signaling and high TMB. To the best of our knowledge, the present study is the first to comprehensively investigate the clinical and genetic characteristics of patients with hypermutant lung cancer in a Chinese population. The results of the current study suggested that hypermutant lung cancer exerted distinctive clinical and genetic features, which may be used as complementary indicators for screening patients sensitive to immunotherapy.
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April-2021
Volume 21 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Zhang H, Wang Y, Ji Q, Cai H, Liang X, Xie J, Li H, Wang J, Zhu G, Tian E, Tian E, et al: Clinicopathological and molecular characteristics of patients with hypermutant lung cancer: A retrospective cohort study. Oncol Lett 21: 329, 2021
APA
Zhang, H., Wang, Y., Ji, Q., Cai, H., Liang, X., Xie, J. ... Zhao, M. (2021). Clinicopathological and molecular characteristics of patients with hypermutant lung cancer: A retrospective cohort study. Oncology Letters, 21, 329. https://doi.org/10.3892/ol.2021.12590
MLA
Zhang, H., Wang, Y., Ji, Q., Cai, H., Liang, X., Xie, J., Li, H., Wang, J., Zhu, G., Tian, E., Zhu, L., Yuan, M., Chen, R., Zhao, M."Clinicopathological and molecular characteristics of patients with hypermutant lung cancer: A retrospective cohort study". Oncology Letters 21.4 (2021): 329.
Chicago
Zhang, H., Wang, Y., Ji, Q., Cai, H., Liang, X., Xie, J., Li, H., Wang, J., Zhu, G., Tian, E., Zhu, L., Yuan, M., Chen, R., Zhao, M."Clinicopathological and molecular characteristics of patients with hypermutant lung cancer: A retrospective cohort study". Oncology Letters 21, no. 4 (2021): 329. https://doi.org/10.3892/ol.2021.12590