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SPARC gene variants predict clinical outcome in locally advanced and metastatic pancreatic cancer patients

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Abstract

Secreted protein acidic and rich in cysteine (SPARC) is a glycoprotein of the extracellular matrix whose expression can be altered in malignant pancreatic cells and in the adjacent stromal fibroblasts. We evaluated the possible role of SPARC gene variants as prognostic markers for locally advanced and metastatic pancreatic cancer. We analyzed eight tagging single-nucleotide polymorphisms (TagSNPs) in the SPARC gene in 74 patients with pancreatic ductal adenocarcinoma treated with chemotherapy alone or combined with radiotherapy. TagSNPs were chosen using the HapMap genome browser and Haploview software 4.2 based on two predefined criteria: (1) coefficient cutoff of 0.80 and (2) minor allele frequency (MAF) ≥ 0.10. Univariate analyses revealed significant associations between four SNPs (rs17718347, rs2347128, rs3210714, and rs967527) and PFS. The rs3210714 genetic variant was also associated with OS. In the multivariate analyses, rs17718347 (HR 0.4; 95% CI 0.2–0.8; p = 0.013) and rs2347128 (HR 0.5; 95% CI 0.3–0.9; p = 0.049) remained statistically associated with PFS. In addition, patients harboring the T-A-G haplotype (rs17718347, rs1978707, rs2347128) had a better PFS (p = 0.002). Our findings suggest that SPARC polymorphisms may be useful in predicting outcome in patients with locally advanced and metastatic pancreatic cancer.

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Acknowledgements

The authors thank Carolyn Newey for English language editing.

Funding

Ana Sebio is the recipient of a Juan Rodes contract from the Instituto de Salud Carlos III (JR/00006).

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Author notes

  1. Cristina Arqueros and Juliana Salazar contributed equally to this study.

Authors and Affiliations

  1. Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, C/Sant Quintí, 89, 08026, Barcelona, Spain

    Cristina Arqueros, Ana Sebio, Ivana Sullivan, María Tobeña, Marta Martín-Richard, Agustí Barnadas & David Páez

  2. Department of Genetics, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain

    Juliana Salazar & Montserrat Baiget

  3. CIBERER U-705, Barcelona, Spain

    Juliana Salazar

  4. Fundació Docència i Recerca Mútua Terrassa, Terrassa, Spain

    M. J. Arranz

  5. Department of Biochemistry, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain

    Josefina Mora

Authors
  1. Cristina Arqueros
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  2. Juliana Salazar
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  4. Ana Sebio
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Correspondence to David Páez.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study before tumor tissue and peripheral blood samples were obtained.

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Arqueros, C., Salazar, J., Arranz, M.J. et al. SPARC gene variants predict clinical outcome in locally advanced and metastatic pancreatic cancer patients. Med Oncol 34, 136 (2017). https://doi.org/10.1007/s12032-017-0993-3

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  • DOI: https://doi.org/10.1007/s12032-017-0993-3

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