Pancreatic cancer (PC) is still a lethal disease and has a poor prognosis, gemcitabine-based chemotherapy is now the standard regimen in the treatment of pancreatic cancer. Gemcitabine resistance is an important obstacle for effective treatment of patients and improvement in patients’ overall survival (OS) and disease free survival (DFS).
We collected the surgical pathological tissue of pancreatic cancer patients who received radical surgery in our hospital from September 2004 to December 2014 continuously. 375 pancreatic cancer tissues and paired adjacent non-tumor tissues were employed for the construction of 4 tissue microarrays (TMAs). The quality of 4 TMAs was reexamined by HE staining. We did immunohistochemistry analysis to test hENT1 expression. The hENT1 antibody was used to measure hENT1 expression in TMAs by IHC staining according to standard protocols. Statistical analyses were performed using SPSS 22.0. The clinical end points of patients were calculated using Kaplan-Meier analysis and differences compared by log-rank test. Cox regression (proportional hazards model) was applied to determine the prognostic values of multivariate factors on patients’ overall survival (OS) and disease free survival (DFS).
The hENT1 protein expression in tumor tissues was much lower than in normal tissues (80.5±8.8 versus 89.5±8.9, p=0.005). A low hENT1 expression level indicated a significant poor outcome of 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). A high hENT1 expression level was related to longer DFS (35.7±4.0 versus 20.6±2.7; p<0.0001). Similarly, patients with high hENT1 expression in gemcitabine-treated group showed longer overall survival OS compared with low expression group (39.4±4.0 versus 31.5±3.9, p=0.001). In contrast, no significant difference of DFS and OS was found in non-gemcitabine treated group between the expression level of hENT1 and the prognosis of patients (p=0.413 and p=0.152). A low hENT1 expression level in tumor tissues was an independent risk factor for PC recurrence or metastasis(HR 0.53; 95% CI: 0.39-0.72; p<0.001). In addition, a low expression level of hENT1 (HR 0.60; 95%CI: 0.43-0.82; p=0.001) was independent risk factors for overall survival of PC. Low hENT1 expression level predicted worse OS (HR 0.60; 95%CI: 0.43-0.82; p=0.002) and DFS (HR 0.56; 95%CI: 0.41-0.77; p<0.001) .
hENT1 was low expressed in tumor tissues and this decreased expression level indicated a worse outcome (including shortened OS and DFS) in patients who received gemcitabine treatment postoperatively.