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Association between polymorphisms of BAG-1 and XPD and chemotherapy sensitivity in advanced non-small-cell lung cancer patients treated with vinorelbine combined cisplatin regimen

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Tumor Biology

Abstract

BCL-2 Associated athanogene 1 (BAG-1) and Xeroderma pigmentosum group D (XPD) are involved in the nucleotide excision repair pathway and DNA repair. We aimed to investigate whether polymorphisms in BAG-1 and XPD have effects on chemotherapy sensitivity and survival in patients with advanced non-small-cell lung cancer (NSCLC) treated with vinorelbine combined cisplatin (NP) regimen. A total of 142 patients with diagnosed advanced NSCLC were recruited in the current study. NP regimen was applied for all eligible patients. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for BAG-1 (codon 324) and XPD (codons 312 and 751) genotyping. The treatment response was evaluated according to the RECIST guidelines. Progression-free survival (PFS) and overall survival (OS) were record as median and end point, respectively. As for BAG-1 codon 324, the chemotherapy sensitivity in NSCLC patients with CT genotype was 0.383 times of those with CC genotype (P < 0.05). With respect to XPD codon 751, the chemotherapy sensitivity in NSCLC patients with Lys/Gln genotype was 0.400 times of those with Lys/Lys genotype (P < 0.05). In addition, NSCLC patients carrying combined C/C genotype at codon 324 in BAG-1, Asp/Asp of XPD codon 312, and Lys/Lys of XPD codon 751 produced a higher efficacy of NP chemotherapy compared to those carrying mutation genotypes (all P < 0.05). Further, there were significant differences in PFS between patients with combined C/C genotype of BAG-1 codon 324, Lys/Lys genotype of XPD codon 751, and Asp/Asp genotype of XPD codon 312 and patients carrying BAG-1 codon 324 C/T genotype, XPD codon751 Lys/Gln genotype, and XPD codon312 Asp/Asn genotype (P < 0.05). Multivariate Cox regression analysis indicated that the combined wild-type of codon 324 XPD, codon 751 XPD, and codon 312 BAG-1 is the protective factor for OS and PFS, and clinical stages is the risk factor for OS and PFS. In conclusion, our research demonstrated the combined effects of BAG-1 and XPD polymorphisms on chemotherapy sensitivity and survival in patients with advanced NSCLC, which might be the important predictive markers for platinum-based chemotherapy efficacy.

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Acknowledgments

We would like to acknowledge the helpful comments on this paper received from our reviewers.

Conflicts of interest

We declare that we have no conflicts of interest.

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    Authors and Affiliations

    1. Department of Oncology, The First Affiliated Hospital of Liaoning Medical University, Five Section of Renmin Street No. 2, Guta District, Jinzhou, 121000, People’s Republic of China

      Ping Li & Min-Wen Ha

    2. Department of Oncology, The Third Affiliated Hospital of Liaoning Medical University, Jinzhou, 121000, People’s Republic of China

      Ya-Di Wang

    3. Department of Oncology, Binzhou Medical University Hospital, Binzhou, 256603, People’s Republic of China

      Jian Cheng

    4. Department of Thoracic Surgery, Hubei Rongjun Hospital, Wuhan, 430079, People’s Republic of China

      Jun-Chen Chen

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    1. Ping Li
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    Correspondence to Min-Wen Ha.

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    Ping Li and Ya-Di Wang contributed equally to this work.

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    Li, P., Wang, YD., Cheng, J. et al. Association between polymorphisms of BAG-1 and XPD and chemotherapy sensitivity in advanced non-small-cell lung cancer patients treated with vinorelbine combined cisplatin regimen. Tumor Biol. 36, 9465–9473 (2015). https://doi.org/10.1007/s13277-015-3672-z

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