Pancreatic cancer (PCA) is one of the most lethal malignancies worldwide with a 5-year survival rate of 9%. Despite the advances in the field, the need for an earlier detection and effective therapies is paramount. PCA high heterogeneity suggests that epigenetic alterations play a key role in tumour development. However, only few epigenetic biomarkers or therapeutic targets have been identified so far. Here we explored the potential of distinct DNA methylation signatures as biomarkers for early detection and prognosis of PCA. PI3K/AKT-related genes differentially expressed in PCA were identified using the Pancreatic Expression Database (n = 153). Methylation data from PCA patients was obtained from The Cancer Genome Atlas (n = 183), crossed with clinical data to evaluate the biomarker potential of the epigenetic signatures identified and validated in independent cohorts. The majority of selected genes presented higher expression and hypomethylation in tumour tissue. The methylation signatures of specific genes in the PI3K/AKT pathway could distinguish normal from malignant tissue at initial disease stages with AUC > 0.8, revealing their potential as PCA diagnostic tools. ITGA4, SFN, ITGA2, and PIK3R1 methylation levels could be independent prognostic indicators of patients’ survival. Methylation status of SFN and PIK3R1 were also associated with disease recurrence. Our study reveals that the methylation levels of PIK3/AKT genes involved in PCA could be used to diagnose and predict patients’ clinical outcome with high sensitivity and specificity. These results provide new evidence of the potential of epigenetic alterations as biomarkers for disease screening and management and highlight possible therapeutic targets.

Pancreatic cystic lesions (PCLs) are a heterogeneous group of lesions with increasing incidence, usually identified incidentally on imaging studies (multidetector computed tomography (MDCT), magnetic resonance imaging (MRI), or endoscopic ultrasound (EUS))

Directed differentiation of hepatocytes from induced pluripotent stem cells (iPSCs) holds promise as source material for treating some liver disorders. The unlimited availability of perfectly differentiated iPSC-derived hepatocytes will dramatically facilitate cell therapies. While systems to manufacture large quantities of iPSC-derived cells have been developed, we have been unable to generate and maintain stable and mature adult liver cells ex vivo. This short review highlights important challenges and possible solutions to the current state of hepatocyte biofabrication for cellular therapies to treat liver diseases. Successful cell transplantation will require optimizing the best cell function, overcoming limitations to cell numbers and safety, as well as a number of other challenges. Collaboration among scientists, clinicians, and industry is critical for generating new autologous stem cell-based therapies to treat liver diseases.