The high stromal SPARC expression is independently associated with poor survival of patients with resected pancreatic ductal adenocarcinoma treated with adjuvant gemcitabine in combination with S-1 or adjuvant gemcitabine alone

Pancreatology. 2018 Mar;18(2):191-197. doi: 10.1016/j.pan.2017.12.014. Epub 2017 Dec 26.

Abstract

Background: Although postoperative adjuvant chemotherapy for pancreatic ductal adenocarcinoma (PDAC) improves survival, its efficacy varies among individuals. Identification of biomarkers that can predict the efficacy of adjuvant chemotherapy for PDAC is essential.

Objectives: To investigate the predictive value of secreted protein acidic and rich in cysteine (SPARC) expression in patients with PDAC treated with adjuvant gemcitabine in combination with S-1 (adjuvant GS) or adjuvant gemcitabine alone (adjuvant G alone).

Methods: Stromal SPARC and cytoplasmic SPARC were examined immunohistochemically in 211 PDAC patients treated with adjuvant GS or G alone after resection. The association of SPARC expression with clinicopathological factors, disease-free survival (DFS) and overall survival (OS) were analyzed.

Results: In multivariate analysis, borderline resectable with arterial contact (BR-A) (P = .002), higher preoperative CA 19-9 level (≥91 U/ml) (P = .005), moderately or poorly (P = .003), presence of lymph node metastasis (P = .012) and high stromal SPARC expression (P = .013) were independent predictors of poor DFS. Moreover, BR-A (P = .003), higher preoperative CA 19-9 level (≥91 U/ml) (P = .007) and high stromal SPARC expression (P < .001) were identified as independent predictors of poor OS. In contrast, cytoplasmic SPARC expression did not affect DFS and OS.

Conclusions: High stromal SPARC expression was an independent predictor of poor DFS and OS in patients treated with adjuvant GS or G alone. Stromal SPARC expression could be a relevant biomarker for prediction of prognosis in PDAC patients after resection treated with adjuvant GS or G alone.

Keywords: Gemcitabine; Pancreatic cancer; Secreted protein acidic and rich in cysteine.

MeSH terms

  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Carcinoma, Pancreatic Ductal / mortality*
  • Carcinoma, Pancreatic Ductal / pathology
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Drug Combinations
  • Female
  • Gemcitabine
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Male
  • Osteonectin / genetics
  • Osteonectin / metabolism*
  • Oxonic Acid / administration & dosage
  • Oxonic Acid / therapeutic use*
  • Retrospective Studies
  • Survival Analysis
  • Tegafur / administration & dosage
  • Tegafur / therapeutic use*

Substances

  • Antineoplastic Agents
  • Drug Combinations
  • Osteonectin
  • SPARC protein, human
  • Deoxycytidine
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid
  • Gemcitabine