SSAT - The Expression of Putative Pancreatic Stem Cell Marker DCAMKL-1 Is Elevated in Early Stage Pancreatic Adenocarcinoma Patients

The Expression of Putative Pancreatic Stem Cell Marker DCAMKL-1 Is Elevated in Early Stage Pancreatic Adenocarcinoma Patients
Jeremy J. Johnson^*¹, Dongfeng Qu², Sripathi M. Sureban^2,3, Randal May^2,3, Stanley Lightfoot⁵, Lewis a. Hassell⁵, Shubham Pant⁴, Russell G. Postier^1,3, Courtney W. Houchen^2,3
¹Surgery, The University of Oklahoma Health Sciences Center, Oklahoma City, OK; ²Medicine / Gastroenterology, OUHSC, Oklahoma City, OK; ³Veterans Affairs Medical Center, Oklahoma City, OK; ⁴Medicine/Hematology and Oncology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK; ⁵Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK

Background: Pancreatic ductal adenocarcinoma carries a grave prognosis with the majority of patients presenting with locally advanced or metastatic disease. Patients diagnosed with early stage pancreatic cancer are often candidates for surgical resection and have improved overall 5 year survival. Doublecortin and CaM kinase-like-1 (DCAMKL-1), a microtubule-associated kinase, is a putative intestinal and pancreatic stem cell marker. We have previously demonstrated that DCAMKL-1 is upregulated in multiple cancers. The aims of this study are to determine the plasma expression level of DCAMKL-1 in pancreatic cancer patients by stage, and to measure the tissue expression level of DCAMKL-1 in this patient population.
Methods: Purified plasma samples from controls (n = 10) and stage I (n = 9), II (n=15), III (n = 14) and IV (n = 11) pancreatic cancer patients were subjected to Western blot and ELISA analysis. Surgical cancer specimens and normal pancreas (commercial tissue array) were immunostained for DCAMKL-1. An independent pathologist scored the immunohistochemical staining based on intensity and tissue involvement. Samples of tumor and adjacent normal tissue from pancreatic surgical specimens were homogenized. Total RNA isolated from these samples was subjected to real-time PCR to measure mRNA expression levels.
Results: We observed greater than a 2.5-fold increase in plasma DCAMKL-1 in patients with stage I pancreatic cancer compared to controls by Western blot analysis (p<0.05). We also observed increased DCAMKL-1 expression by ELISA: stage I (3.42-fold, p = 0.07); II (4.1-fold, p<0.05); III (2.06-fold, p>0.05) and IV (1.15-fold, p>0.05). There were similar DCAMKL-1 mRNA expression levels in both stage II and III tumor tissues (n = 8). Interestingly, we found that DCAMKL-1 mRNA levels in adjacent tissues are significantly higher than the respective tumor tissues. DCAMKL-1 mRNA levels were higher in the adjacent tissues compared to the respective tumor tissues of stage II (7-fold) and stage III (2.7-fold) patients. Furthermore, we observed increased DCAMKL-1 immunostaining in all stages of cancer compared to controls. Although there were no significant differences between the stages, we observed increased stromal staining compared to the epithelium within the specimens.
Conclusion: These data suggest that DCAMKL-1 is increased in all stages of pancreatic cancer tissues. Additionally, the higher DCAMKL-1 level in the tissue adjacent to the tumor may suggest a premalignant condition in this tissue. Furthermore, DCAMKL-1 is elevated in plasma of stage I and II patients, suggesting that it may potentially be used as a biomarker for the early detection of pancreatic cancer.

Back to Annual Meeting Program