DOI: 10.1177/11795549261473797 ISSN: 1179-5549
CXCL12
Expression and Clinicopathological Features at the Invasive Front of Pancreatic Cancer
Shunsuke Imamura, Takeshi Uehara, Mai Iwaya, Shiho Asaka, Shinsuke Sugenoya, Hiroshi Sawaguchi, Takahiro Yoshizawa, Yasuhiro Kuraishi, Tomoyuki Nakajima, Shotaro Komamura, Akira Nakamura, Yugo Iwaya, Akira Shimizu, Yuji Soejima, Hiroyoshi Ota, Tadanobu Nagaya
Background
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.
Methods
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)
.
Results
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.
Conclusion
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.