Journal of Clinical Hepatology
Diabetes and pancreatic cancer frequently occur together, but the biological effects of high blood glucose on tumour progression remain unclear. This study focused on YAP1, a regulator of cell growth, and COL6A1, a component of the extracellular matrix surrounding cells.
The researchers combined public genomic data, pancreatic cancer cells, a diabetic mouse model and tumour samples from 96 patients. Half of the patients had both pancreatic cancer and diabetes, while the remainder had pancreatic cancer without diabetes.
YAP1 and COL6A1 were both highly expressed in pancreatic cancer and showed a strong positive relationship. Pathway analysis linked them to extracellular matrix interactions, Hippo signalling and PI3K–AKT signalling.
Culturing pancreatic cancer cells under high-glucose conditions increased both RNA and protein expression of YAP1 and COL6A1. Their expression was also elevated in tumours from diabetic mice and in tissue from patients with pancreatic cancer and diabetes.
High expression of either protein was associated with poorer survival. Two-year survival was 6.82% among patients with high YAP1 expression, compared with 25.00% among those with lower expression. YAP1 and COL6A1 remained independently associated with prognosis after adjustment for other clinical factors.
The results suggest one possible mechanism connecting hyperglycaemia with more aggressive pancreatic cancer: elevated glucose may activate growth signalling and alter the extracellular environment through YAP1 and COL6A1.
These proteins could become biomarkers for identifying high-risk patients or targets for future treatments. The findings also support further investigation of glucose control as part of pancreatic cancer care.
However, the clinical analysis included only 96 patients and was observational. Diabetes involves metabolic changes beyond elevated glucose, so the patient data cannot isolate glucose as the cause. The cell and mouse experiments support a biological connection but do not establish that inhibiting either protein will improve patient survival.
Objective: To investigate the changes in the expression levels of Yes-associated protein 1 (YAP1) and human collagen type Ⅵ alpha 1...
