Prognostic relevance of ribonucleotide reductase small subunit p53R2 in pancreatic cancer

Abstract

e15655 Background: Pancreatic cancer has the worst survival of any solid tumor, with most patients presenting with metastatic disease. Even after surgical resection the median survival is only 20 months suggesting micrometastatic disease. Ribonucleotide reductase is a critical enzyme in DNA synthesis and repair. Previous studies have shown that ribonucleotide reductase M2 (RRM2) subunit is associated with invasion and metastasis. Even though p53R2 has 80% homology to RRM2, its role is quite different. Here we report on the prognostic relevance of p53R2 in pancreatic cancer. Methods: Archived pathology specimens were obtained from 30 patients and immunohistochemistry for p53R2 performed on an IRB approved protocol (#06253). Clinical data was obtained by chart review and log-rank and Cox hazard proportional models were used to analyze overall and disease-free survival. Cell culture analysis was performed to further evaluate the role of p53R2. Utilizing a Matrigel chamber, invasive MiaPaCa-2 cells were collected for comparison to parental cells. Results: The median overall survival (OS) was 13.2 months (p53R2+) vs 8.5 months (p53R2-) (p=0.01). Disease free survival (DFS) was 12.4 vs 8.5 months respectively (p<0.05). By Western analysis, invasive cells have a higher protein level of RRM2 compared to parental cells. Interestingly, the protein level of p53R2 was low in the invasive cells suggesting an opposing role. To confirm this we inhibited p53R2 using siRNA which enhanced the migration ability of Mia PaCa-2 cells. Conclusions: Patients with p53R2 expression have improved disease-free and overall survival suggesting this may be used as a prognostic marker in pancreatic cancer patients. No significant financial relationships to disclose.