Imaging heterogeneity in the mitochondrial redox state of premalignant pancreas in the pancreas-specific PTEN-null transgenic mouse model

All methods show consistently that the PTEN deficient pancreases (Pdx1-Cre;PTENlox/lox) were significantly more heterogeneous in their mitochondrial redox state compared to the controls (PTENlox/lox). Statistical analysis taking into account the variations of the redox state with tissue depth further shows that PTEN deletion significantly shifted the pancreatic tissue to an overall more oxidized state. Oxidization of the PTEN-null group was not seen when the imaging data were analyzed by global averaging without considering the variation of the redox indices along tissue depth, indicating the importance of taking tissue heterogeneity into account for the statistical analysis of the multi-section imaging data.This study reveals a possible link between the mitochondrial redox state alteration of the pancreas and its malignant transformation and may be further developed for establishing potential metabolic biomarkers for the early diagnosis of pancreatic cancer.Pancreatic cancer ranking the fourth leading cause of cancer-related deaths in the United States has the incidence rate approaching the mortality rate [1,2]. The main reason is that at the time of diagnosis 80-85% patients are already present with locally advanced or metastatic disease that prevents curative surgery [3-5]. The etiology of PC is unclear and more than 90% of PC patients acquire the disease sporadically. The early detection of PC is therefore critical to improving the survival rate and reducing the mortality rate. Currently there is no reliable biomarker available for the early diagnosis of PC. Although the most common biomarker for PC, serum carbohydrate antigen 19-9 (CA 19-9) secreted by the exocrine pancreas cells has up to 90% specificity to symptomatic patients, low positive predictive value in asymptomatic patients, false negative results in Lewis negative phenotype, and increased false positivity in the presence of obstructive jaundice limit its usefulness for the early detection of PC [6].