title: Prognostic role of human equilibrative transporter 1 (hENT1) in patients with resected gastric cancer.
abstract: Nucleoside transporter proteins are specialized proteins that mediate the transport of nucleosides and nucleoside analog drugs across the plasma membrane. The human equilibrative nucleoside transporter 1 (hENT1) is a member of these proteins and mediates cellular entry of gemcitabine, cytarabine, and fludarabine. The hENT1 expression has been demonstrated to be related with prognosis and activity of gemcitabine-based therapy in breast, ampullary, lung, and pancreatic cancer. We investigated the immunohistochemical expression of hENT in tumor samples from 111 patients with resected gastric adenocarcinoma, correlating these data with clinical parameters and disease outcomes. None of the patients received chemotherapy or radiation therapy before or after surgery as a part of an adjuvant or neoadjuvant program. On univariate survival analysis, the hENT1 expression was associated with overall survival (OS) and disease free survival (DFS). Specifically, those patients with overexpression of hENT1 showed a shorter OS (P = 0.021) and a shorter DFS (P = 0.033). Considering only the node positive patients, higher hENT levels were associated with significantly shorter median DFS (21.7 months; 95% CI 11.1-32.4) compared with patients with low expression of hENT1. The hENT1 expression was defined, in the lymph-node positive patients, as an independent prognostic factor (P = 0.019). Furthermore, considering only patients with diffuse or mixed tumors and lymph-node positive, the expression of hENT1 was strongly related with DFS and OS. Immunohistochemistry for the hENT1 protein carries prognostic information in patients with resected gastric cancer and holds promise as a predictive factor in chemotherapy decisions.
authors.affiliation: Medical Oncology, University Campus Bio-Medico, Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.forename: Maria Elisabetta
authors.initials: ME
authors.lastname: Fratto
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Perrone
authors.forename: Raymond
authors.initials: R
authors.lastname: Lai
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Catalano
authors.forename: Carol
authors.initials: C
authors.lastname: Cass
authors.forename: Pier Adelchi
authors.initials: PA
authors.lastname: Ruffini
authors.forename: Chiara
authors.initials: C
authors.lastname: Spoto
authors.forename: Pietro
authors.initials: P
authors.lastname: Muretto
authors.forename: Sergio
authors.initials: S
authors.lastname: Rizzo
authors.forename: Andrea Onetti
authors.initials: AO
authors.lastname: Muda
authors.forename: John R
authors.initials: JR
authors.lastname: Mackey
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tonini
authors.forename: Francesco
authors.initials: F
authors.lastname: Graziano
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000378:metabolism / Q000493:pharmacokinetics; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D015331:Cohort Studies; D018450:Disease Progression; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D033721:Equilibrative Nucleoside Transporter 1 / Q000032:analysis / Q000378:metabolism*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000503:physiopathology; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000517:prevention & control; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D033721:Equilibrative Nucleoside Transporter 1; C438649:SLC29A1 protein, human