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

• Published in: Medical oncology (Northwood, London, England) London, England), 2017-08, Vol.34 (8), p.136-136, Article 136
• Main Authors: Arqueros, Cristina, Salazar, Juliana, Arranz, M. J., Sebio, Ana, Mora, Josefina, Sullivan, Ivana, Tobeña, María, Martín-Richard, Marta, Barnadas, Agustí, Baiget, Montserrat, Páez, David
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adenocarcinoma - therapy; Aged; Carcinoma, Pancreatic Ductal - genetics; Carcinoma, Pancreatic Ductal - mortality; Carcinoma, Pancreatic Ductal - therapy; Computer Simulation; Female; Gene Frequency; Haplotypes; Hematology; Humans; Internal Medicine; Male; Medicine; Medicine & Public Health; Metastasis; Multivariate Analysis; Oncology; Original Paper; Osteonectin - genetics; Pancreatic cancer; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - therapy; Pathology; Polymorphism; Polymorphism, Single Nucleotide; Survival Analysis; Treatment Outcome
• ISSN: 1357-0560; 1559-131X
• DOI: 10.1007/s12032-017-0993-3

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.