A multi-omics machine learning framework in predicting the recurrence and metastasis of patients with pancreatic adenocarcinoma.

Local recurrence and distant metastasis are the main causes of death in patients with pancreatic adenocarcinoma (PDAC). Microbial content in PDAC metastasis is still not well-characterized. Here, the tissue microbiome was comprehensively compared between metastatic and non-metastatic PDAC patients. We found that the pancreatic tissue microbiome of metastatic patients was significantly different from that of non-metastatic patients. Further, 10 potential bacterial biomarkers (Kurthia, Gulbenkiania, Acetobacterium and Planctomyces etc.) were identified by differential analysis. Meanwhile, significant differences in expression patterns across multiple omics (lncRNA, miRNA, and mRNA) of PDAC patients were found. The highest accuracy was achieved when these 10 bacterial biomarkers were used as features to predict recurrence or metastasis in PDAC patients, with an AUC of 0.815. Finally, the recurrence and metastasis in PDAC patients were associated with reduced survival and this association was potentially driven by the 10 biomarkers we identified. Our studies highlight the association between the tissue microbiome and recurrence or metastasis of pancreatic adenocarcioma patients, as well as the survival of patients.

ZNF655 accelerates progression of pancreatic cancer by promoting the binding of E2F1 and CDK1.

Pancreatic cancer has an extremely terrible prognosis and is a common cause of cancer death. In this study, the clinic value, biological function and underlying mechanisms of Zinc finger protein 655 (ZNF655) in human pancreatic cancer were evaluated. The expression level of ZNF655 in pancreatic cancer was determined by immunohistochemistry (IHC) staining. The biological effects of ZNF655 in pancreatic cancer cells was investigated by loss/gain-of-function assays in vitro and in vivo. The downstream molecular mechanism of ZNF655 was explored using co-immunoprecipitation (Co-IP), dual-luciferase reporter and chromatin immunoprecipitation (Ch-IP). ZNF655 expression was significantly elevated in human pancreatic cancer and possessed clinical value in predicting poor prognosis. Functionally, ZNF655 knockdown inhibited the biological progression of pancreatic cancer cells, which was characterized by weaken proliferation, enhanced apoptosis, arrested cell cycle in G2, impeded migration, and suppressed tumor growth. Mechanistically, ZNF655 played an important role in promoting the binding of E2F transcription factor 1 (E2F1) to the cyclin-dependent kinase 1 (CDK1) promoter. Furthermore, knockdown of CDK1 alleviated the promoting effects of ZNF655 overexpression in pancreatic cancer cells. The promotive role of ZNF655 in pancreatic cancer via CDK1 was determined, which drew further interest regarding its clinical application as a promising therapeutic target.