Ann Hepatobiliary Pancreat Surg.  2020 May;24(2):127-136. 10.14701/ahbps.2020.24.2.127.

Human equilibrative nucleoside transporter-1 (hENT1) and ribonucleotide reductase regulatory subunit M1 (RRM1) expression; do they have survival impact to pancreatic cancer?

• Hwang DW
• Shin E
• Cho JY
• Han HS
• Yoon YS

• KMID: 2500772
• DOI: http://doi.org/10.14701/ahbps.2020.24.2.127

Abstract

Backgrounds/Aims
Gemcitabine is still one of adjuvant options in chemotherapeutic agent for pancreatic ductal adenocarcinoma (PDAC). Integral membrane transporter protein and intracellular enzymes including human equilibrative nucleoside transporter 1 (hENT1), deoxycytidine kinase (dCK), ribonucleotide reductase (RR) M1, and M2 are known as important factors for chemosensitivity of gemcitabine. We aimed to investigate the correlation between these key molecules and 5-year actual survival in PDAC patients.
Methods
The expression of intratumoral hENT1, dCK, RRM1, and RRM2 was assessed immunohistochemically in 160 PDAC patients underwent surgical resection. Association between clininopathologic factors, immunohistochemical results, and overall survival were analyzed.
Results
Adjuvant chemotherapy including concurrent chemoradiotherapy was not associated with overall survival (HR, 0.92; 95% CI, 0.65-1.31; p=0.658). High hENT1 expression group did not show statistical survival difference, compared with all others (HR, 1.16; 95% CI, 0.82-1.65, p=0.396). Gemcitabine therapy and high hENT1 group was compared with all other patients, and no difference in overall survival was identified (HR, 0.99; 95% CI, 0.68-1.42; p=0.940). And, gemcitabine therapy and high hENT1 group did not differ statistically from gemcitabine therapy and low hENT1 expression (HR, 0.92; 95% CI, 0.55-1.56; p=0.764). The intensity of dCK, RRM1, and RRM2 expression was not associated with overall survival (p=0.413, p=0.138 and p=0.061) in univariate analysis.
Conclusions
The expression of hENT1, dCK, RRM1 and RRM2 may not be associated with overall survival for patients with pancreatic cancer on gemcitabine adjuvant therapy. These proteins and other factors that may interact with or confound these results should be investigated in the near future.

Keyword

Pancreatic ductal adenocarcinoma; Adjuvant chemotherapy; Gemcitabine; hENT1; Overall survival; Surgery

Figure

• 

  Fig. 1 Kaplan-Meier survival curves. (A) Comparison of overall survival based on intensity of intratumoral hENT1 expression. There was no significant difference in overall survival. (B) High hENT1 expression group was compared with low hENT1 expression group, there was no statistical survival difference (HR, 1.16; 95% CI, 0.82-1.65, p=0.396). (C) When the group with gemcitabine therapy and high hENT1 expression was compared with all other patients, and no difference in overall survival was identified (HR, 0.99; 95% CI, 0.68-1.42; p=0.940).

• 

  Fig. 2 Kaplan-Meier survival curves. The association between intratumoral hENT1 expression and overall survival according to adjuvant chemotherapeutic agent. (A) Overall survival between the intensity of hENT1 expression within patients with gemcitabine therapy (HR, 0.92; 95% CI, 0.55-1.56; p=0.764). (B) The comparison between gemcitabine with high hENT1 expression group and other chemotherapy with low hENT1 did not show significant survival difference (HR, 0.81; 95% CI, 0.49-1.32; p=0.394).

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