Human equilibrative nucleoside transporter 1 (hENT1) levels predict response to gemcitabine in patients with biliary tract cancer (BTC).
OBJECTIVE
Translational data suggest that nucleoside transporters, in particular human equilibrative nucleoside transporter 1 (hENT1), play an important role in predicting clinical outcome after gemcitabine chemotherapy for several types of cancer. The aim of this study was to retrospectively determine patients' outcome according to the expression of hENT1 in tumoral cells of patients receiving gemcitabine-based therapy.


METHODS
The immunohistochemistry analysis was performed on samples from thirty-one patients with unresectable biliary tract cancer (BTC) consecutively treated with first line gemcitabine-based regimens.


RESULTS
Positive hENT1 staining patients were 21 (67.7%); negative hENT1 staining patients were 10 (32.3%). Statistical analysis revealed no association between baseline characteristics, toxicities and tumor response to gemcitabine and hENT1 levels. In the univariate analysis, HENT1 expression was significantly correlated with time to progression (TTP) (p=0.0394; HR 2.902, 95%CI 1.053-7.996). The median TTP was 6.33 versus 2.83 months, respectively in patients with positive versus negative hENT1 staining. Moreover, patients with positive hENT1 expression showed a longer median overall survival when compared with patients with low hENT1 expression (14 versus 7 months, respectively), but this difference did not reach the statistical significance (p=0.128).


CONCLUSIONS
Therefore, hENT1 may be a relevant predictive marker of benefit from gemcitabine-based therapies in patients with advanced BTC.
Santini
Daniele
D
Medical Oncology, University Campus Bio-Medico, Rome, Italy. d.santini@unicampus.it
Schiavon
Gaia
G
Vincenzi
Bruno
B
Cass
Carol E
CE
Vasile
Enrico
E
Manazza
Andrea D
AD
Catalano
Vincenzo
V
Baldi
Giacomo Giulio
GG
Lai
Raymond
R
Rizzo
Sergio
S
Giacobino
Alice
A
Chiusa
Luigi
L
Caraglia
Michele
M
Russo
Antonio
A
Mackey
John
J
Falcone
Alfredo
A
Tonini
Giuseppe
G
D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D033721:Equilibrative Nucleoside Transporter 1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D033721:Equilibrative Nucleoside Transporter 1; C438649:SLC29A1 protein, human; D003841:Deoxycytidine; D000093542:Gemcitabine