Human Equilibrative Nucleoside Transporter 1: Novel Biomarker and Prognostic Indicator for Patients with Gemcitabine-Treated Pancreatic Cancer

Aim: This article aimed to find appropriate pancreatic cancer (PC) patients to treat with Gemcitabine with better survival outcomes by detecting hENT1 levels.<br /> Methods: We collected surgical pathological tissues from PC patients who received radical surgery in our hospital from September 2004 to December 2014. A total of 375 PC tissues and paired adjacent nontumor tissues were employed for the construction of 4 tissue microarrays (TMAs). The quality of the 4 TMAs was examined by HE staining. We performed immunohistochemistry analysis to evaluate hENT1 expression in the TMAs. Moreover, we detected hENT1 expression level and proved the role of hENT1 in cell proliferation, drug resistance, migration and invasion in vivo and vitro.<br /> Results: The results indicated that low hENT1 expression indicated a significantly poor outcome in PC patients, including shortened DFS (21.6 +/- 2.8 months versus 36.9 +/- 4.0 months, p< 0.001) and OS (33.6 +/- 3.9 versus 39.6 +/- 3.9, p=0.004). Meanwhile, patients in stage I/II of TNM stage had a longer OS (40.2 +/- 3.4 versus 15.4 +/- 1.7, p=0.002) and DFS (31.0 +/- 3.1 versus 12.4 +/- 1.9, p=0.016) than patients in stage III/IV. Patients in M0 stage had a longer OS (39.7 +/- 3.4 versus 16.2 +/- 1.9, p=0.026) and DFS(30.7 +/- 3.0 versus 11.8 +/- 2.2, p=0.031) than patients in M1 stage, and patients with tumors not invading the capsule had a better DFS than those with tumor invasion into the capsule (30.8 +/- 3.0 versus 12.6 +/- 2.3, p=0.053). Patients with preoperative CA19-9 values <= 467 U/mL have longer DFS than that of patients who had preoperative CA19-9 values > 467 U/mL (37.9 +/- 4.1 versus 22.9 +/- 4.0, p=0.04). In the subgroup analysis, a high hENT1 expression level was related to a longer OS(39.4 +/- 4.0 versus 31.5 +/- 3.9, p=0.001) and DFS(35.7 +/- 4.0 versus 20.6 +/- 2.7; p< 0.0001) in the Gemcitabine subgroup.<br /> Conclusion: PC patients with high hENT1 expression have a better survival outcomes when receiving Gemcitabine. hENT1 expression can be a great prognostic indicator for PC patients to receive Gemcitabine treatment.