IL-17 signaling pathway in SPP1+ macrophages drives digestive tract cancer progression

IL-17 signaling pathway in SPP1 D macrophages drives digestive tract cancer progressionDigestive tract cancers (DTCs) are cancers that occur in the gastrointestinal tract and related organs, including esophageal, gastric, and colorectal cancer.Since these types of cancer share similar endoderm developmental origins, the genomic and other molecular features can possess many similarities.Therefore, it is urgent to explore the commonalities of molecular characteristics and signaling pathways in the tumor microenvironment among these diseases.To uncover the shared molecular characteristics in DTCs, we obtained the recent RNA sequence profiles from The Cancer Genome Atlas (TCGA) database, encompassing esophageal carcinoma (ESCA), stomach adenocarcinoma (STAD), and colon adenocarcinoma (COAD).Differentially expressed gene (DEG) analysis revealed that ESCA exhibited 376 up-regulated and 626 down-regulated mRNAs, STAD showed 872 up-regulated and 769 down-regulated mRNAs, and COAD had 1123 up-regulated and 939 down-regulated mRNAs (Fig. 1A; Fig. S1A andTable 1).To investigate the existence of co-expression of DEGs in DTCs, we employed Venn diagrams to analyze the overlapping and distinct DEGs in DTCs (Fig. 1B).Subsequently, we explored the relevant signaling pathways associated with these DEGs in the mentioned cancer types using the DAVID tool.Based on the number of genes involved, we prioritized the first eight signal pathways with the highest gene enrichment (Fig. S1B).Additionally, we constructed a proteineprotein interaction network complex involving common DEGs to identify key differentially expressed core genes within these cancer types.As shown in Figure 1C, sixteen core genes were identified, of which seven were up-regulated (including CXCL1/5/6/8), indicating that the CXCL family might play a critical role in DTCs.