J Cancer 2022; 13(15):3701-3709. doi:10.7150/jca.78498 This issue Cite

Research Paper

Exonuclease 1 genetic variant is associated with clinical outcomes of pemetrexed chemotherapy in lung adenocarcinoma

Mi Jeong Hong1,2*, Ji Eun Park3*, Shin Yup Lee3✉, Jang Hyuck Lee1,2, Jin Eun Choi1,2, Hyo-Gyoung Kang1,2, Sook Kyung Do1,2, Ji Yun Jeong5, Kyung Min Shin6, Won Ki Lee7, Yangki Seok8, Sun Ha Choi3, Yong Hoon Lee3, Hyewon Seo3, Seung Soo Yoo3, Jaehee Lee3, Seung Ick Cha3, Chang Ho Kim3, Jae Yong Park1,2,3,4✉

1. Department of Biochemistry, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
2. Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea.
3. Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
4. BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Korea.
5. Department of Pathology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
6. Department of Radiology School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
7. Medical Research Collaboration Center in Kyungpook National University Hospital and School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
8. Department of Thoracic Surgery, Soonchunhyang University Gumi Hospital, Gumi, Korea.
*These authors contributed equally to this work.

Citation:
Hong MJ, Park JE, Lee SY, Lee JH, Choi JE, Kang HG, Do SK, Jeong JY, Shin KM, Lee WK, Seok Y, Choi SH, Lee YH, Seo H, Yoo SS, Lee J, Cha SI, Kim CH, Park JY. Exonuclease 1 genetic variant is associated with clinical outcomes of pemetrexed chemotherapy in lung adenocarcinoma. J Cancer 2022; 13(15):3701-3709. doi:10.7150/jca.78498. https://www.jcancer.org/v13p3701.htm
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Abstract

Graphic abstract

Pemetrexed is an anti-folate agent which is one of the most frequently used chemotherapy agents for non-squamous non-small cell lung cancer (NSCLC) patients. However, clinical response to pemetrexed chemotherapy and survival outcome of patients varies significantly. We evaluated whether the genetic variants in miRNA target sites may affect the treatment outcome of pemetrexed chemotherapy in lung adenocarcinoma patients. One hundred SNPs in miRNA binding regions in cancer-related genes were obtained from the crosslinking, ligation, and sequencing of hybrids (CLASH) and CancerGenes database, and the associations with the response to pemetrexed chemotherapy and survival outcomes were investigated in 314 lung adenocarcinoma patients. Two polymorphisms, EXO1 rs1047840G>A and CAMKK2 rs1653586G>T, were significantly associated with worse chemotherapy response (adjusted odds ratio [aOR] = 0.41, 95% CI = 0.24-0.68, P = 0.001, under dominant model; and aOR = 0.33, 95% CI = 0.16-0.67, P = 0.002, under dominant model, respectively) and worse OS (adjusted hazard ratio [aHR] = 1.34, 95% CI = 1.01-1.77, P = 0.04, under dominant model; and aHR = 1.50, 95% CI = 1.06-2.13, P = 0.02, under dominant model, respectively) in multivariate analyses. Significantly increased luciferase activity was noted in EXO1 rs1047840 A allele compared to G allele. In conclusion, two SNPs in miRNA binding sites, especially EXO1 rs1047840G>A, were associated with the chemotherapy response and survival outcome in lung adenocarcinoma patients treated with pemetrexed.

Keywords: lung adenocarcinoma, miRNA target sites, genetic variants, chemotherapy, response, survival


Citation styles

APA
Hong, M.J., Park, J.E., Lee, S.Y., Lee, J.H., Choi, J.E., Kang, H.G., Do, S.K., Jeong, J.Y., Shin, K.M., Lee, W.K., Seok, Y., Choi, S.H., Lee, Y.H., Seo, H., Yoo, S.S., Lee, J., Cha, S.I., Kim, C.H., Park, J.Y. (2022). Exonuclease 1 genetic variant is associated with clinical outcomes of pemetrexed chemotherapy in lung adenocarcinoma. Journal of Cancer, 13(15), 3701-3709. https://doi.org/10.7150/jca.78498.

ACS
Hong, M.J.; Park, J.E.; Lee, S.Y.; Lee, J.H.; Choi, J.E.; Kang, H.G.; Do, S.K.; Jeong, J.Y.; Shin, K.M.; Lee, W.K.; Seok, Y.; Choi, S.H.; Lee, Y.H.; Seo, H.; Yoo, S.S.; Lee, J.; Cha, S.I.; Kim, C.H.; Park, J.Y. Exonuclease 1 genetic variant is associated with clinical outcomes of pemetrexed chemotherapy in lung adenocarcinoma. J. Cancer 2022, 13 (15), 3701-3709. DOI: 10.7150/jca.78498.

NLM
Hong MJ, Park JE, Lee SY, Lee JH, Choi JE, Kang HG, Do SK, Jeong JY, Shin KM, Lee WK, Seok Y, Choi SH, Lee YH, Seo H, Yoo SS, Lee J, Cha SI, Kim CH, Park JY. Exonuclease 1 genetic variant is associated with clinical outcomes of pemetrexed chemotherapy in lung adenocarcinoma. J Cancer 2022; 13(15):3701-3709. doi:10.7150/jca.78498. https://www.jcancer.org/v13p3701.htm

CSE
Hong MJ, Park JE, Lee SY, Lee JH, Choi JE, Kang HG, Do SK, Jeong JY, Shin KM, Lee WK, Seok Y, Choi SH, Lee YH, Seo H, Yoo SS, Lee J, Cha SI, Kim CH, Park JY. 2022. Exonuclease 1 genetic variant is associated with clinical outcomes of pemetrexed chemotherapy in lung adenocarcinoma. J Cancer. 13(15):3701-3709.

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