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

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

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

Open access
Zou, Ting, Liu, Jun Yan, Qin, Qun, Guo, Jie, Zhou, Wen Zhi, Li, Xiang Ping, Zhou, Honghao, Chen, Juan, Liu, Zhao Qian·2023·Biomedicines
DOI 10.20944/preprints202310.0897.v1PMC PMC10741124

Preprint — published as 10.3390/biomedicines11123133 · Paper page

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Abstract

Background: Lung cancer is still the most lethal malignancy in the world from the report of Cancer Statistics in 2021. Platinum-based chemotherapy combined immunotherapy is the first-line treatment in lung cancer patients. However, the 5-year survival rate always affected by the adverse reaction and drug resistance caused by platinum-based chemotherapy. DNA damage and repair system is one of the important mechanisms which can affect the response to chemotherapy and clinical outcome 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 in 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 by 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 treat by platinum-based chemotherapy (p=0.031*). We also discovered that the polymorphisms in rs873601 was significantly associated with the prognosis in age more than 55 years, Small Cell Lung Cancer (SCLC) and smoking patients, Long Intergenic Non-protein Coding RNA (PNKY) rs2444933 in age less than 55 years, SCLC, metastasis and stage III/IV/ED patients, Short Tau Inversion Recovery (STIR1) rs3740051 in SCLC and metastasis patients, PNKY rs1869641 in SCLC patients, XRCC5 rs1051685 in non-metastasis patients, respectively. Conclusion: The ERCC5 rs873601(G>A) maybe a valuable biomarker for predicting the prognosis in lung cancer patients treated with platinum-based chemotherapy. Statements and Declarations: The authors declare that they have no conflict of interest.

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Figures

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., Chen, J., & Liu, Z. Q.
Affiliations
Central South University (CN)
Corresponding author
Chen, Juan
ORCID
Venue
Biomedicines
Publisher
MDPI AG
Published
2023-10-13
Volume
11
Issue
12
Pages
3133-3133
ISSN
2227-9059 (ISSN-L)
DOI
10.20944/preprints202310.0897.v1
PMC
PMC10741124
OpenAlex
W4388969272
Cited by
10
References
1
Citations by year
2026: 4 · 2025: 1 · 2024: 4 · 2023: 1
FWCI
1.84
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 (2021 JC0002, 82173901, kh2003010, kq2208408)
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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