Overview
- The study, published Thursday in Cancer Discovery, used donated whole human pancreases to compare PanIN precursor lesions, normal pancreas and tumors.
- Researchers applied single-cell RNA sequencing and spatial transcriptomics to isolate rare PanINs and map cells and gene activity at high resolution.
- They found PanIN epithelial cells progressively adopt cancer-like gene programs while the surrounding stroma remains like normal pancreas until later events.
- Progression to invasive cancer coincides with large-scale rearrangement of myeloid and lymphoid cells and the emergence of cancer-specific fibroblasts marked by high SMA, LRRC15, and LEF1.
- Because most PanINs do not become cancer, the team says external stressors such as inflammation, pancreatitis, smoking, age or obesity may trigger stromal reprogramming and represent targets for early diagnosis or interception.