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Cited by 10Lung Cancer Treatments and MutationsLung Cancer Research StudiesGenetic Associations and Epidemiology

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Role of rs873601 Polymorphisms in Prognosis of Lung Cancer Patients Treated with Platinum-Based Chemotherapy

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Zou, Ting, Liu, Jun-Yan, Qin, Qun, Guo, Jie, Zhou, Wen-Zhi, Li, Xiang-Ping, Zhou, Hong-Hao, Chen, Juan, Liu, Zhao-Qian·2023·Biomedicines
DOI 10.3390/biomedicines11123133PMC PMC10741124

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Abstract

Background: Lung cancer is still the most lethal malignancy in the world, according to the report of Cancer Statistics in 2021. Platinum-based chemotherapy combined with immunotherapy is the first-line treatment in lung cancer patients. However, the 5-year survival rate is always affected by the adverse reactions and drug resistance caused by platinum-based chemotherapy. DNA damage and repair system is one of the important mechanisms that can affect the response to chemotherapy and clinical outcomes in lung cancer patients. Objective: The objective of this study is to find the relationship between the polymorphisms of DNA repair genes with the prognosis of platinum-based chemotherapy in lung cancer patients. Patients and Methods: We performed genotyping in 17 single nucleotide polymorphisms (SNPs) of Excision Repair Cross-Complementation group (ERCC) genes and X-ray Repair Cross-Complementing (XRCC) genes of 345 lung cancer patients via Sequenom MassARRAY. We used Cox proportional hazard models, state, and plink to analyze the associations between SNPs and the prognosis of lung cancer patients. Results: We found that the ERCC5 rs873601 was associated with the overall survival time in lung cancer patients treated with platinum-based chemotherapy (p = 0.031). There were some polymorphisms that were related to the prognosis in specific subgroups of lung cancer. Rs873601 showed a great influence on the prognosis of patients more than 55 years, Small Cell Lung Cancer (SCLC), and smoking patients. Rs2444933 was associated with prognosis in age less than 55 years, SCLC, metastasis, and stage III/IV/ED patients. Rs3740051 played an important role in the prognosis of SCLC and metastasis patients. Rs1869641 was involved in the prognosis of SCLC patients. Rs1051685 was related to the prognosis in non-metastasis patients. Conclusion: The ERCC5 rs873601 (G>A) was a valuable biomarker for predicting the prognosis in lung cancer patients treated with platinum-based chemotherapy.

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Figure 1 The ERCC5 rs873601 polymorphisms are significantly associated with the prognosis in lung cancer patients treated with platinum-based chemotherapy, and the A variant allele of ERCC5 rs873601 are protective allele. Patients who carry the AA or GA genotypes have a longer MST-OS than GG (p = 0.031 *). The dashed line, the overall survival rate is 0.5 or 50%.
Figure 1 The ERCC5 rs873601 polymorphisms are significantly associated with the prognosis in lung cancer patients treated with platinum-based chemotherapy, and the A variant allele of ERCC5 rs873601 are protective allele. Patients who carry the AA or GA genotypes have a longer MST-OS than GG (p = 0.031 *). The dashed line, the overall survival rate is 0.5 or 50%.CC BY · PubMed Central
Figure 2 The polymorphisms of ERCC5 rs873601, PNKY rs2444933, and STIR1 rs1051685 were related to the overall survival (OS) significantly. (A) The ERCC5 rs873601 polymorphisms were significantly associated with the overall survival (OS) in age > 56 and smoking patients. (B) The variants of PNKY rs2444933 were related to the prognosis significantly in age ≤ 56, metastasis, non-smoker, and clinical in III/IV/ED patients. (C) The polymorphisms of STIR1 rs3740051 were significantly associated with the overall survival in SCLC and metastasis patients. Dashed line, merged BETA value. *, p < 0.05.
Figure 2 The polymorphisms of ERCC5 rs873601, PNKY rs2444933, and STIR1 rs1051685 were related to the overall survival (OS) significantly. (A) The ERCC5 rs873601 polymorphisms were significantly associated with the overall survival (OS) in age > 56 and smoking patients. (B) The variants of PNKY rs2444933 were related to the prognosis significantly in age ≤ 56, metastasis, non-smoker, and clinical in III/IV/ED patients. (C) The polymorphisms of STIR1 rs3740051 were significantly associated with the overall survival in SCLC and metastasis patients. Dashed line, merged BETA value. *, p < 0.05.CC BY · PubMed Central
Figure 3 The polymorphisms of ERCC5 rs873601, PNKY rs2444933, rs1849641, and XRCC5 rs1051685 were significant with the progress-free survival (PFS) significantly. (A–C) The ERCC5 rs873601, PNKY rs2444933, and rs1869641 polymorphisms were significantly associated with progression-free survival (PFS) in SCLC patients. (D) The variants of XRCC5 rs1051685 were related to the prognosis significantly in non-metastasis patients. Dashed line, merged BETA value. *, p < 0.05.
Figure 3 The polymorphisms of ERCC5 rs873601, PNKY rs2444933, rs1849641, and XRCC5 rs1051685 were significant with the progress-free survival (PFS) significantly. (A–C) The ERCC5 rs873601, PNKY rs2444933, and rs1869641 polymorphisms were significantly associated with progression-free survival (PFS) in SCLC patients. (D) The variants of XRCC5 rs1051685 were related to the prognosis significantly in non-metastasis patients. Dashed line, merged BETA value. *, p < 0.05.CC BY · PubMed Central
Figure 4 The polymorphisms of ERCC5 rs873601 can affect the prognosis of lung cancer patients. Rs873601 is a mutation located in the 3′UTR of ERCC5, it can affect the mRNA of ERCC5 to translation protein. It can also regulate the RNA-binding protein and the protein-to-protein interaction of ERCC5. These may have an influence on the DNA damage and repair in the NER pathway, which is a vital regulator in the prognosis of lung cancer patients treated with platinum-based chemotherapy.
Figure 4 The polymorphisms of ERCC5 rs873601 can affect the prognosis of lung cancer patients. Rs873601 is a mutation located in the 3′UTR of ERCC5, it can affect the mRNA of ERCC5 to translation protein. It can also regulate the RNA-binding protein and the protein-to-protein interaction of ERCC5. These may have an influence on the DNA damage and repair in the NER pathway, which is a vital regulator in the prognosis of lung cancer patients treated with platinum-based chemotherapy.CC BY · PubMed Central

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Metadata

Authors
Zou, T., Liu, J.-Y., Qin, Q., Guo, J., Zhou, W.-Z., Li, X.-P., Zhou, H.-H., Chen, J., & Liu, Z.-Q.
Affiliations
  • Central South University (CN)
  • Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha 410008, China
  • Department of Pharmacy, National Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Changsha 410008, China
  • Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya Hospital, Central South University, Changsha 410078, China
Corresponding author
Chen, Juan
ORCID
Venue
Biomedicines
Publisher
MDPI AG
Published
2023-11-24
Volume
11
Issue
12
Pages
3133
ISSN
2227-9059 (ISSN-L)
DOI
10.3390/biomedicines11123133
PMC
PMC10741124
OpenAlex
W4388969272
Cited by
10
References
3
Citations by year
2026: 4 · 2025: 1 · 2024: 4 · 2023: 1
FWCI
1.83
Type
journal article
Language
en
Open access
Licence
Locations
  • Biomedicines (publishedVersion, cc-by)
  • Preprints.org (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (82173901, 2021 JC0002, kq2208408, kh2003010)
  • Major Project of Natural Science Foundation of Hunan Province (82173901, 2021 JC0002, kq2208408, kh2003010)
  • Changsha Municipal Natural Science Foundation (82173901, 2021 JC0002, kq2208408, kh2003010)
  • Major Science and Technology Program of Changsha (82173901, 2021 JC0002, kq2208408, kh2003010)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
  • Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
lung cancer, single nucleotide polymorphisms, DNA repair genes, platinum-based chemotherapy, prognosis, small cell lung cancer, smoking, metastasis, prognostic factors

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