Expression Landscape of Cancer-Foxp3 and its Prognostic Value in Pancreatic Adenocarcinoma

Abstract

FOXP3, a key identifier of Treg, has also been identified in tumor cells, which is referred to as cancer-FOXP3 (c-FOXP3). Human c-FOXP3 undergoes multiple alternative splicing events, generating several isoforms, like c-FOXP3FL and c-FOXP3Δ3. Previous research on c-FOXP3 often ignore its cellular source (immune or tumor cells) and isoform expression patterns, which may obscure our understanding of its clinical significance. Our immunohistochemistry investigations which conducted across 18 tumors using validated c-FOXP3 antibodies revealed distinct expression landscapes for c-FOXP3 and its variants, with the majority of tumors exhibited a predominantly expression of c-FOXP3Δ3. In pancreatic adenocarcinoma (PAAD), we further discovered a potential link between nuclear c-FOXP3Δ3 in tumor cells and poor prognosis. Overexpression of c-FOXP3Δ3 in tumor cells was associated with metastasis. This work elucidates the expression pattern of c-FOXP3 in pan-cancer and indicates its potential as a prognostic biomarker in clinical settings, offering new perspectives for its clinical application

Note:
Funding declaration: This work was supported by National Science Foundation of China (No. 82125026; 82330081), the Taishan Scholars Program of Shandong Province (No. Ts20190987) and the Major State Basic Research Development Program of Natural Science Foundation of Shandong Province (No. ZR2020ZD11) to H. Ren. The National Science Foundation of China (No. 82303933) to Q. Yu. Natural Science Foundation of Shandong (No. ZR2023QH122) to J. Wang, and Shandong Province Postdoctoral Innovation Talent Program (No.SDBX2022022) to Y. Zhang.

Conflict of Interests: The authors declared no conflict of interest.

Ethical Approval: The usage of these specimens was approved by the Ethics Committee of the Affiliated Hospital of Qingdao University (Permission No. QYFYWZLL28015).

Keywords: cancer-FOXP3, splice variants, antibodies, pan-cancer, prognosis