Background: Environmental pollution was a global problem that caused great damage to human health. Perfluorodecanoic acid (PFDA) and perfluorooctane sulfonic acid (PFOS), as members of perfluoroalkyl and polyfluoroalkyl substances (PFASs), were considered as “permanent environmental pollutants,” and have been reported to be risk factors in cancer. Research has reported that the exposure to PFASs increased the risk of developing glioma, and PFDA and PFOS promoted glioblastoma (GBM) cells proliferation. However, research linking PFASs exposure to GBM prognosis is lacking. Methods: This study utilized network toxicology and bioinformatics analysis to elucidate the potential mechanism of PFDA and PFOS on GBM. Functional experiments were conducted to verify the biological function of PFDA/PFOS target genes on GBM. Results: Seven target genes of PFDA/PFOS were identified as being specifically and abnormally expressed in GBM, with AUC values reaching 0.95 for CTSB, 0.95 for CHI3L1, 0.84 for VEGFA, 0.95 for MMP2, 0.96 for FAM83D, 0.98 for MMP9, and 0.97 for HOXD10 in TCGA cohort. PFDA/PFOS exposure related GBM prognosis model based on XGBoost algorithm, with the highest C-index reaching 0.84, uncovering that PFDA/PFOS may affect the prognosis via FN1, CHI3L1 and HOXD10. Molecular docking results verified the interactions between PFDA/PFOS and the identified genes. The VinaScore was −7.4 kcal/mol between FN1 and PFOS, −8.1 kcal/mol between CHI3L1 and PFOS, and −6.2 kcal/mol between HOXD10 and PFDA. In vitro experiments proved the roles that the prognostic genes contributed to the maligant behaviors of GBM. Conclusions: This study combined bioinformatics and network toxicology analysis strategies to identified hub genes potentially mediating the effects of PFDA/PFOS, providing evidences that PFDA/PFOS exposure have a potential association with GBM prognosis. Our study emphasized the need for further epidemiological and clinical studies.
Chen et al. (Wed,) studied this question.