Overexpression of ST8Sia1 inhibits tumor progression by TGF-β1 signaling in rectal adenocarcinoma and promotes the tumoricidal effects of CD8+ T cells by granzyme B and perforin.

Background: Rectal adenocarcinoma (READ) involves the dysregulated expression of alpha 2,8-Sialyltransferase1 (ST8Sia1) although its role during READ's progression is unclear.

Methods: The mRNA level of ST8Sia1 was analyzed based on The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Tumor Immune Estimation Resource (TIMER) 2.0. Furthermore, the prognostic and significance of ST8Sia1 in READ was assessed through Kaplan-Meier curve, univariate, multivariate Cox regression, and receiver operating characteristic (ROC) methods. The role of ST8Sia1 in the READ immune microenvironment was explored using ESTIMATE analysis and TIMER databases. Furthermore, the expression of ST8Sia1 in tissues was analyzed using real-time quantitative polymerase chain reaction (RT-qPCR), western blotting (WB), and immunohistochemistry (IHC). Perforin and Granzyme B secretion by CD8⁺ T cells, as well as tumor cell apoptosis, were detected after co-culturing CD8⁺ T cells with READ tumor cells and ST8Sia1-overexpression (ST8Sia1-OE) tumor cells. Furthermore, we examined the interaction between ST8Sia1 and TGF-β1 in READ cells.

Results: ST8Sia1 exhibited excellent diagnostic capability for READ, with positive correlations to immune response and negative correlations to tumor purity. Increased levels of perforin and Granzyme B from CD8⁺ T cells were observed in vitro, enhancing tumor cell apoptosis. ST8Sia1 interacts with TGF-β1, mediating its inhibitory effects on READ development.

Conclusions: ST8Sia1 is a potential diagnostic biomarker and therapeutic target for READ, enhancing CD8⁺ T cell function and possibly improving patient outcomes through cellular immunotherapy.