Identification of Mutations Associated with Response to Pemetrexed-Based Chemotherapy in Lung Adenocarcinoma Using Next-Generation Sequencing

Tian Qing, Zhao Ming, Chen Siyu, Wang Yuqi, Li Zong Wei and Liu Yang

Department of Thoracic Cancer, PLA General Hospital, China

^*Correspondance to: Liu Yang 

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Abstract:

Purpose: Pemetrexed, an inhibitor of Thymidylate Synthase (TS) and other folate-dependent enzymes, is used as standard of treatment for patients with advanced non-squamous non-small-cell lung cancer. We tried to identify SNPs associated with response to pemetrexed-based chemotherapy in lung adenocarcinoma.
Patients and Methods: We retrospectively reviewed the metastatic lung adenocarcinoma patients who received pemetrexed-based chemotherapy at thoracic surgery department of PLA general hospital between February 2013 and December 2018. The patients with Complete Response (CR) or Partial Response (PR) were sorted to the good response group, while those with Stable Disease (SD)
or Progression Disease (PD) to the no response group. Illumina sequencing system was applied to sequence the genome of tumor tissues.
Results: Of 19 enrolled patients, 14 patients showed PR and were sorted to the good response group, and the 5 patients experienced SD or PD and were regarded as having no response. Eleven SNPs in nine genes are significantly associated with good response to pemetrexed-based chemotherapy, while twenty-two SNPs in fifteen genes with no response. Eleven SNPs in nine genes are significantly associated with good response to pemetrexed-based chemotherapy, while twenty-two SNPs in fifteen genes with no response. Seven SNPs in gene UGT1A5 (UDP glucuronosyltransferase family 1 member A5) were demonstrated to associated with no response simultaneously.
Conclusion: Few mutations were found to be associated with response to pemetrexed-based chemotherapy in lung adenocarcinoma. Perspective clinical research was warranted to obtain the sensitivity and specificity of these mutations as predictive biomarkers.

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Cite the Article:

Qing T, Ming Z, Siyu C, Yuqi W, Wei LZ, Yang L. Identification of Mutations Associated with Response to Pemetrexed-Based Chemotherapy in Lung Adenocarcinoma Using Next-Generation Sequencing. Clin Oncol. 2020;5:1736..