CXCL12 Expression and Clinicopathological Features at the Invasive Front of Pancreatic Cancer

The clinical significance of CXC ligand 12 (CXCL12) expression at the invasive front of pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study examined the expression of stromal CXCL12 using RNAscope for direct visualization of RNA localization and compared expression profiles with clinicopathological findings.

This retrospective investigation analyzed CXCL12 expression in 66 PDAC tissue samples, specifically where the cancer had infiltrated the peripancreatic fatty tissue, using RNAscope. RNA expression was quantified and categorized into high and low groups for evaluating associations with clinicopathological data. Single-cell RNA sequencing (scRNA-seq) was employed to elucidate cellular expression patterns of CXCL12 and its receptor, C-X-C motif chemokine receptor 4 (CXCR4).

CXCL12-positive staining was found in 88% of samples, with expression predominantly in the stroma rather than in tumor cells. Venous invasion was significantly less in the high CXCL12 expression group (P = 0.019). We observed no significant difference in overall survival between the high and low CXCL12 expression groups (P = 0.233), although relapse-free survival showed a trend toward being longer in the high CXCL12 expression group (P = 0.0673). scRNA-seq revealed that CXCL12 was predominantly produced by fibroblasts and endothelial cells, while its CXCR4 receptor was expressed mainly on T cells, B cells, and myeloid cells.

RNAscope findings revealed that stromal CXCL12 expression was associated with reduced PDAC progression and may represent a marker of favorable prognosis. Further studies are needed to confirm its role and prognostic value.