Advanced Science (Feb 2021)

Mutational Profile Evaluates Response and Survival to First‐Line Chemotherapy in Lung Cancer

  • Yayi He,
  • Lele Song,
  • Hao Wang,
  • Peixin Chen,
  • Yu Liu,
  • Hui Sun,
  • Xiaobin Li,
  • Shiying Dang,
  • Guifeng Liu,
  • Xinyi Liu,
  • Shifu Chen,
  • Xiaoni Zhang,
  • Paul Hofman,
  • Junji Uchino,
  • Henry S. Park,
  • Jose M. Pacheco,
  • Fabrizio Tabbò,
  • Mingyan Xu,
  • Jiawei Dai,
  • Kan He,
  • Yang Yang,
  • Caicun Zhou,
  • written on behalf of the AME Lung Cancer Collaborative Group

DOI
https://doi.org/10.1002/advs.202003263
Journal volume & issue
Vol. 8, no. 4
pp. n/a – n/a

Abstract

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Abstract Evaluating the therapeutic response and survival of lung cancer patients receiving first‐line chemotherapy has always been difficult. Limited biomarkers for evaluation exist and as a result histology represents an empiric tool to guide therapeutic decision making. In this study, molecular signatures associated with response and long‐term survival of lung cancer patients receiving first‐line chemotherapy are discovered. Whole‐exome sequencing is performed on pretherapeutic tissue samples of 186 patients [145 non‐small cell lung cancer (NSCLC) and 41 small cell lung cancer (SCLC)]. On the basis of genomic alteration characteristics, NSCLC patients can be classified into four subtypes (C1–C4). The long‐term survival is similar among different subtypes. SCLC patients are also divided into four subtypes and significant difference in their progression free survival is revealed (P < 0.001). NSCLC patients can be divided into three subtypes (S1–S3) based on TMB. A trend of worse survival associated with higher TMB in subtype S3 than in S1+S2 is found. In contrast, no significant correlations between molecular subtype and therapeutic response are observed. In conclusion, this study identifies several molecular signatures associated with response and survival to first‐line chemotherapy in lung cancer.

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