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. 2019 Jun;110(6):2014-2021.
doi: 10.1111/cas.14032. Epub 2019 May 22.

Association between certain non-small cell lung cancer driver mutations and predictive markers for chemotherapy or programmed death-ligand 1 inhibition

Wenhua Liang  1 , Minzhang Guo  1 , Zhenkui Pan  2 , Xiuyu Cai  3 , Caichen Li  1 , Yi Zhao  1 , Hengrui Liang  1 , Haiying Yang  4 , Zhen Wang  4 , Wenting Chen  4 , Chuhong Xu  4 , Xinyun Yang  5 , Jianyu Sun  6 , Ping He  7 , Xia Gu  7 , Weiqiang Yin  1 , Jianxing He  1
Affiliations

Association between certain non-small cell lung cancer driver mutations and predictive markers for chemotherapy or programmed death-ligand 1 inhibition

Wenhua Liang et al. Cancer Sci. 2019 Jun.

Abstract

This study aimed to analyze the association between driver mutations and predictive markers for some anti-tumor agents in non-small cell lung cancer (NSCLC). A cohort of 785 Chinese patients with NSCLC who underwent resection from March 2016 to November 2017 in the First Affiliated Hospital of Guangzhou Medical University was investigated. The specimens were subjected to hybridization capture and sequence of 8 important NSCLC-related driver genes. In addition, the slides were tested for PD-L1, excision repair cross-complementation group 1 (ERCC1), ribonucleotide reductase subunit M1 (RRM1), thymidylate synthase (TS) and β-tubulin III by immunohistochemical staining. A total of 498 (63.4%) patients had at least 1 driver gene alteration. Wild-type, EGFR rare mutation (mut), ALK fusion (fus), RAS mut, RET fus and MET mut had relatively higher proportions of lower ERCC1 expression. EGFR 19del, EGFR L858R, EGFR rare mut, ALK fus, HER2 mut, ROS1 fus and MET mut were more likely to have TS low expression. Wild-type, EGFR L858R, EGFR rare mut and BRAF mut were associated with lower β-tubulin III expression. In addition, wild-type, RAS mut, ROS1 fus, BRAF and MET mut had higher proportion of PD-L1 high expression. As a pilot validation, 21 wild-type patients with advanced NSCLC showed better depth of response and response rate to taxanes compared with pemetrexed/gemcitabine (31.2%/60.0% vs 26.6%/45.5%). Our study may aid in selecting the optimal salvage regimen after targeted therapy failure, or the chemo-regimen where targeted therapy has not been a routine option. Further validation is warranted.

Keywords: chemotherapy; gene mutation; lung cancer; predictive markers; programmed death-ligand 1.

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Figures

Figure 1
Figure 1
The examples representing different expression levels of ERCC1, RRM1, TS, β‐tubulin III and PD‐L1. −~+, ++ and +++ measure the expression of ERCC1, RRM1, TS and β‐tubulin III. 1%, 50% and 100% for PD‐L1
Figure 2
Figure 2
Correlation between driver mutations and predictive markers
See this image and copyright information in PMC

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