Abstract
Colon cancer represents a global health challenge. The 3'-phosphoadenosine 5'-phosphosulfate (PAPS) synthase 2 (PAPSS2) is the key enzyme to generate PAPS, which is the universal sulfonate donor for all sulfation reactions. However, the correlation between PAPSS2 and diagnosis, prognosis, and immune cell infiltration in colon adenocarcinoma (COAD) has rarely been mentioned. We analyzed PAPSS2 expression levels in pan-cancer from The Cancer Genome Atlas (TCGA) database; and validated it in the Gene Expression Omnibus (GEO) database. RNA-seq data were analyzed using the R package to identify differentially expressed genes (DEGs) between COAD tissues with high and low PAPSS2 expression from multiple databases. The ssGSEA algorithm was used to analyze the correlation between PAPSS2 and immune cell infiltration in COAD. Tumor tissues and normal tissues were classified and assayed at the single-cell level to analyze differences in PAPSS2 expression. CCK8 and EdU assays were used to validate proliferative capacity; wound healing assays to validate migratory capacity; and Transwell assays to examine changes in invasive capacity. The PAPSS2 expression level was significantly lower in the tumor tissues and associated with worse clinical parameters and prognosis in COAD patients. And we constructed a transcriptional regulatory network involving FLI1 and hsa-miR-152-3p targeting PAPSS2 to support the role of PAPSS2.Enrichment analysis revealed that PAPSS2 is involved in O-glycan biosynthesis, TP53 pathway and extracellular matrix formation. PAPSS2 was found to be positively associated with the infiltration of numerous immune cells, immunomodulatory factors and chemokines. Cytological experiments demonstrated that PAPSS2 knockdown enhanced the proliferation, migration, and invasion of HCT116 and HT-29 cells. Our study suggests that PAPSS2 acts as a promising diagnostic and prognostic biomarker, which facilitates malignant progression in part through its regulation of the p53 signaling pathway.