Combined Analyses of hENT1, TS, and DPD Predict Outcomes of Borderline-resectable Pancreatic Cancer

Anticancer Res. 2017 May;37(5):2465-2476. doi: 10.21873/anticanres.11587.

Abstract

Background: Predicting chemosensitivity to neoadjuvant chemoradiotherapy (NACRT) in pancreatic cancer is desired. The present study aimed to examine the relationship between intratumoral expression of human equilibrative nucleoside transporter 1 (hENT1), thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD) and the outcomes of NACRT with gemcitabine (GEM) combined with S-1 in patients with borderline-resectable pancreatic cancer (BRPC).

Materials and methods: Forty-seven patients who underwent NACRT with GEM plus S-1, following curative surgery, were recruited in our Institution between 2009 and 2012. Immunohistochemical expressions of hENT1, TS, and DPD in fine-needle aspiration (FNA) biopsies and resected specimens were examined. The correlation between these enzyme expressions and long-term outcome was analyzed.

Results: In 21 FNA specimens, no relationship between clinical responses to NACRT and long-term survival was found. However, in 47 resected specimens, patients were classified according to the number of favorable hENT1, TS, and DPD expression factors (hENT1 positive/TS negative/DPD negative). The presence of three favorable factors was strongly associated with improved partial response rates to NACRT (p=0.002). Patients with 2 or more favorable factors showed a significantly longer overall survival than the other patients (p=0.002).

Conclusion: Combined expression analyses of hENT1, TS, and DPD may predict long-term outcomes in patients with BRPC after NACRT.

Keywords: DPD; NACRT; TS; borderline-resectable pancreatic cancer; hENT1.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / therapeutic use
  • Biomarkers, Tumor / metabolism*
  • Biopsy, Fine-Needle
  • Chemoradiotherapy
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Dihydrouracil Dehydrogenase (NADP) / metabolism*
  • Drug Combinations
  • Equilibrative Nucleoside Transporter 1 / metabolism*
  • Female
  • Gemcitabine
  • Humans
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Oxonic Acid / therapeutic use
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / surgery
  • Pancreatic Neoplasms / therapy
  • Tegafur / therapeutic use
  • Thymidylate Synthase / metabolism*

Substances

  • Antimetabolites, Antineoplastic
  • Biomarkers, Tumor
  • Drug Combinations
  • Equilibrative Nucleoside Transporter 1
  • SLC29A1 protein, human
  • Deoxycytidine
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid
  • Dihydrouracil Dehydrogenase (NADP)
  • Thymidylate Synthase
  • Gemcitabine