application-laparoscopic-programmatic-neurolymphatic-radical

Application of Laparoscopic Programmatic Neurolymphatic Radical Pancreaticoduodenectomy in Pancreatic Head Cancer

Laparoscopic pancreaticoduodenectomy (LPD) has become a widely adopted surgical approach for treating pancreatic head cancer. Traditional open ...

Southern Medical University

Perineural invasion (PNI) is a pivotal prognostic factor in pancreatic cancer, associated with aggressive tumor behavior and adverse patient outcomes. The recognized clinical impact of PNI highlights the need to better understand the molecular mechanisms underlying PNI-induced phenotypes. In this study, we isolated PNI-associated cancer-associated fibroblasts (pCAF), which demonstrated a markedly enhanced capacity to promote neural invasion in pancreatic cancer compared with non-PNI-associated CAFs. Single-cell, high-throughput sequencing and metabolomics data showed a significant upregulation of glycolysis in pCAFs, fostering a high-lactate tumor microenvironment conducive to cancer progression. pCAF-derived lactate was absorbed by tumor cells, facilitating histone H3K18 lactylation. The lactate-induced epigenetic modification activated the transcription of neural invasion-associated genes, such as L1CAM and SLIT1, thereby driving PNI in pancreatic cancer. Further exploration of metabolic reprogramming in pCAFs revealed enhanced acetylation of the glycolytic enzyme GAPDH, which correlated with increased enzymatic activity and glycolytic flux. Targeting GAPDH and lactylation modifications significantly inhibited neural invasion in a genetically engineered mouse model. Clinical data suggested that high levels of H3K18 lactylation correlate with severe PNI and poorer patient prognosis. Together, these findings provide critical insights into the role of CAFs in promoting PNI of pancreatic cancer, highlighting glycolytic reprogramming and lactate-driven histone modifications as potential therapeutic targets for PDAC.

Cancer-Associated Fibroblasts Foster a High-Lactate Microenvironment to Drive Perineural Invasion in Pancreatic Cancer.

Liver diseases are established risk factors for hepatobiliary and pancreatic cancers. This study explores the relationship between liver disease and hepatobiliary-pancreatic cancers, focusing on transaminase levels and genetic susceptibility.

Article	Year
Cancer-Associated Fibroblasts Foster a High-Lactate Microenvironment to Drive Perineural Invasion in Pancreatic Cancer. Cancer research\| PubMed ID: 40138590	2025
Liver diseases, transaminases, and hepatobiliary-pancreatic cancer risk: a cohort and Mendelian randomisation study using data from UK Biobank. BMJ open gastroenterology\| PubMed ID: 40645641	2025

Honghui Jiang

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