CHST11‐mediated microenvironment events contribute to pulmonary fibrosis and cancer progression

Abstract

The Carbohydrate sulfotransferase (CHST) family is essential for Chondroitin Sulfate synthesis and is associated with cancer progression. Comparing all CHST families, we found that CHST11 has prognostic value than other families. CHST11 is related to the overall survival rate in the pan‐cancer profile, among which lung adenocarcinoma is the most significant. From pulmonary fibrosis to lung cancer, the expression of CHST11 showed a linear increase. We analyzed the CHST11 interactome, and the results indicated that CHST11 contributes to diverse canonical pathways, including immune microenvironment, fibrosis, and cancer progression. Based on the prediction results of Ingenuity Pathway Analysis (IPA), we speculate that CHST11 can secrete IL1B and IL6 signals to activate the upstream regulator IRF8. This is also the key to the fact that IRF8 has contributed to cystic fibrosis and lung cancer progression. In addition, IRF8 can also transactivate CD80 and CD86 to reform the tumor microenvironments and immune response. By reversing the CHST11‐IL6/IL1B‐IRF8‐CD80/CD86 mediated axis, we confirmed that VE821 and LY2603618 have the value of drug repurposing. Our study proves novel insight into how CHST11 contributes to cystic fibrosis and lung cancer by reprogramming the immune microenvironment.