Serine protease PRSS23 drives gastric cancer by enhancing tumor associated macrophage infiltration via FGF2

Abstract

Serine proteases has been considered to be closely associated with the inflammatory response and tumor progression. As a novel serine protease, the biological function of PRSS23 is rarely studied in cancers. In this study, the prognostic significance of PRSS23 was analyzed in two-independent gastric cancer (GC) cohorts. PRSS23 overexpression was clinically correlated with poor prognosis and macrophage infiltration of GC patients. Loss-of-function study verified that PRSS23 plays oncogenic role in GC. RNA-seq, qRT-PCR, western blotting and ELISA assay confirmed that serine protease PRSS23 positively regulated FGF2 expression and secretion. Single-cell analysis and gene expression correlation analysis showed that PRSS23 and FGF2 were high expressed in fibroblasts, and highly co-expressed with the biomarkers of tumor associated macrophages (TAMs), cancer-associated fibroblasts (CAFs) and mesenchymal cells. Functional analysis confirmed PRSS23/FGF2 was required for TAM infiltration. Rescue assay further verified that PRSS23 promotes GC progression and TAM infiltration through FGF2. Survival analysis showed that high infiltration of M1-macrophage predicted favorable prognosis, while high infiltration level of M2-macrophage predicted poor prognosis in GC. Our finding highlights that PRSS23 promotes TAM infiltration through regulating FGF2 expression and secretion, thereby resulting in a poor prognosis.

Cancer-associated fibroblast-secreted IGFBP7 promotes gastric cancer by enhancing tumor associated macrophage infiltration via FGF2/FGFR1/PI3K/AKT axis

“…6B ). Previous studies have reported that FGF2 plays critical roles in macrophage infiltration and polarization [ 22 , 27 – 31 ]. Thus, we analyzed the correlation between IGFBP7 expression and immune infiltration using two methods, including CIBERSORT and TIMER.…”

“…Takase et al reported that FGF2 promotes TAM infiltration and tumor progression in esophageal squamous cell carcinomas through FGF2/FGFR1 axis [ 21 ]. Similarly, Qin and colleagues found that serine protease PRSS23 promotes GC progression by positively regulating FGF2 secretion to enhance TAM infiltration [ 22 ]. In this study, we identified a novel role of IGFBP7 in regulating TAM infiltration by enhancing FGF2 secretion and activating FGF2/FGFR1/PI3K/AKT signaling.…”

Genome-wide association studies identify miRNA-194 as a prognostic biomarker for gastrointestinal cancer by targeting ATP6V1F, PPP1R14B, BTF3L4 and SLC7A5

“…The western blotting assay was performed as previously described ( 46 ). After 72h transfected with miRNA, GIC cells were lysed in RIPA buffer added 1 mM PMSF.…”

Identification of cellular heterogeneity and key signaling pathways associated with vascular remodeling and calcification in young and old primate aortas based on single-cell analysis

“…Statistical analysis was performed with default method in Seurat package. As we previously described [56][57][58][59], the P values for gene expression analysis in different groups were estimated using Wilcoxon Rank Sum test. As for cell communication analysis, statistical analysis was also performed with default method in CellChat package, and default method of "triMean" was used for computing the average gene expression per cell group.…”