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A novel mutation panel for predicting etoposide resistance in small-cell lung cancer

Authors Qiu Z, Lin A, Li K, Lin W, Wang Q, Wei T, Zhu W, Luo P, Zhang J

Received 16 February 2019

Accepted for publication 31 May 2019

Published 21 June 2019 Volume 2019:13 Pages 2021—2041

DOI https://doi.org/10.2147/DDDT.S205633

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Dr Anastasios Lymperopoulos


Zhengang Qiu,1,2,* Anqi Lin,1,* Kun Li,1,* Weiyin Lin,1,* Qiongyao Wang,1 Ting Wei,1 Weiliang Zhu,1 Peng Luo,1 Jian Zhang1

1Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, People’s Republic of China; 2Department of Oncology, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, People’s Republic of China

*These authors contributed equally to this work

Purpose: Platinum-based chemotherapy, consisting of etoposide and cisplatin (EP), has been the cornerstone of therapy for extensive-stage small-cell lung cancer (ES-SCLC) for decades. Despite the marked initial sensitivity of SCLC to chemotherapy, EP regimens cannot avoid the emergence of drug resistance in clinical practice. With the rise of new chemotherapy regimens in recent years and the primary resistance or insensitivity of ES-SCLC to EP regimens, it is desirable to be able to identify patients with resistant or insensitive ES-SCLC.
Methods: The sequencing and drug sensitivity data of SCLC cell lines were provided by The Genomics of Drug Sensitivity in Cancer Project (GDSC). The data regarding sensitivity to etoposide of 54 SCLC cell lines were analyzed, and etoposide-sensitive cell lines and etoposide-resistant cell lines were differentiated according to the IC50 values defined by the GDSC. ROC curve analysis was performed on all mutations and combinations of mutations to select the optimal panel to predict resistance to etoposide.
Results: ROC analysis of etoposide resistance revealed that the most significant single gene mutation indicating resistance to etoposide was CSMD3, and the accuracy of predicting resistance to etoposide proved to be the highest when there was any mutation in CSMD3/PCLO/RYR1/EPB41L3, area under the curve =0.804 (95% confidence interval: 0.679–0.930,P<0.001).
Conclusion: This study found that a panel with four genes (CSMD3, EPB41L3, PCLO, and RYR1) can accurately predict sensitivity to etoposide. These findings provide new insights into the overall treatment for patients with ES-SCLC that is resistant or insensitive to etoposide.

Keywords: small-cell lung carcinoma, etoposide, EP regimens, IP regimens, gene mutation





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