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J Cancer 2020; 11(15):4343-4351. doi:10.7150/jca.44410 This issue Cite

Research Paper

Association of variations in platinum resistance-related genes and prognosis in lung cancer patients

Yuan-Kang Zhou^1,2, Xiang-Ping Li³, Ji-Ye Yin^1,2, Ting Zou⁴, Zhan Wang⁵, Ying Wang⁶, Lei Cao³, Juan Chen^3✉, Zhao-Qian Liu^1,2✉

1. Department of Clinical Pharmacology and National Clinical Research Center for Geriatric Disorder, Xiangya Hospital, Central South University, Changsha 410008, China
2. Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China
3. Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China
4. Department of National Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Changsha 410008, China
5. Department of Lung Cancer and Gastroenterology, Hunan Cancer Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, 410013, China
6. Department of the Central Laboratory, Hunan Cancer Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, 410013, China

✉ Corresponding authors: Zhao-Qian Liu, Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008; China; Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078; China. Tel: +86 731 89753845, Fax: +86 731 82354476, E-mail: zqliuedu.cn or Juan Chen, Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008; China. E-mail: cj1028edu.cn More

Abstract

Purpose: We aimed to investigate the association of single-nucleotide polymorphisms (SNPs) in HMGB1, REV3L, and NFE2L2 with prognosis in lung cancer patients with platinum-based chemotherapy.

Methods: We have recruited 348 lung cancer patients treated with platinum. Log-rank test and Cox regression analysis were used to assess overall survival (OS) and progression-free survival (PFS) among SNP genotypes.

Results: The results revealed that patients carrying TC or CC genotype in REV3L rs462779 (HR=0.67, 95% CI=0.51-0.90, P=0.007) and AG or GG genotype in HMGB1 rs1045411 (HR=0.61, 95% CI=0.38-0.99, P=0.046) had a better overall survival. Additionally, carrying TC or TT genotype in rs462779 had a lower risk (OR=0.38, 95% CI=0.17-0.89, P=0.025) of lymph node metastasis, carrying AG or AA genotype in rs1045411 was significantly related to early T stage (OR=0.47, 95% CI=0.29-0.76, P=0.002). In stratified analysis, patients with TC or CC genotype in rs462779 were significantly associated with overall survival in male patients, never-smokers, patients with younger age (≤56), no family history of cancer, adenocarcinoma, advanced stage (stage III or IV), or ECOG PS 0-1. While patients with AG or GG genotype in rs1045411 were significantly associated with overall survival in patients with advanced stage (stage III or IV) or ECOG PS 0-1.

Conclusion: Our results indicate that the TC or CC genotype in rs462779 and AG or GG genotype in rs1045411 are contributed to better overall survival. The REV3L rs462779 and HMGB1 rs1045411 may serve as prognosis markers in lung cancer patients with platinum-based chemotherapy.

Keywords: lung cancer, platinum-based chemotherapy, prognosis, polymorphisms, REV3L, HMGB1

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