Possible novel non-invasive biomarker for chronic inflammation induced chronic pancreatitis associated malignancy

Objectives: Pancreatic malignancy is a major public health problem worldwide and recent reports indicated that pancreatic cancer will be second most common cause of cancer-related deaths by the end of 2021. The cause of increasing death rate is due to the nonexistence of detection tools to early diagnose, poor prognosis, resistance to chemotherapy and also lack in understanding the mechanism of PDAC pathogenesis. Circulating tumor cells (CTCs) play a major role in metastatic step of intravasation and presence of these cells are strong prognostic marker for the progression of pancreatic malignancy in chronic pancreatitis (CP). Goal: Identifying the novel CTCs in the chronic inflammation mediated experimental model for the progression of malignancy in CP. Methods: We have performed flow cytometer and immunofluorescence analyses were performed in the lymphoid and lung samples to detect CTCs in the chronic inflammation (Cerulin and Azoxymethane) induced CP mouse model.  Results: We report that induced SOX9 positive cells were observed in the blood, lymph node and spleen samples of cerulein with azoximethane (AOM) treated mice compared to cerulein alone. Further, we provide evidence that early metastasis through the migration and homing of mega merged SOX9⁺ and PDX⁺ ductal stem cells (CTCs) in the lungs of cerulein with AOM treated mice. These identified CTCs in experimentally induced malignant pancreatitis may serve as a novel finding to identify a non-invasive biomarker that needs to be examined in the blood of human pancreatic cancer. Conclusions: Taken together, the presented data of identified mega merged SOX9⁺ and PDX⁺ ductal stem cells (CTCs) may serve a non-invasive biomarker for the early detection of pancreatic malignancy and metastasis.