CIBERSORT And Weighted Gene Co?Expression Network Analysis For Identifying Hub Genes In Association With The Infiltration Of M2 Tumor-Associated Macrophages In Prostate Cancer

Objective: The potential mechanism of chemotherapy resistance of docetaxel in prostate cancer is unclear.This study aims to explore the role of M2tumor-associated macrophages in the occurrence and development of chemotherapy resistance in prostate cancer and involve related signaling pathways.Methods and materials: PCa sample data of TCGA was collected and analyzed.The CIBERSORT algorithm was performed to evaluate tumor-infiltrating immune cells based on The Cancer Genome Atlas cohort.It suggests that M2-TAM accounts for a large proportion which was related to the prognosis and clinical pathological stage.Weighted gene co-expression network analysis was conducted to explore the modules related to M2 tumor-associated macrophages and identify the hub genes.Gene Ontology analysis and pathway enrichment analysis were performed for functional annotation and a protein–protein interaction network was built.Samples from TCGA,ICGC database and the Human Protein Atlas database were used as validation sets.PC3 cells were transfected with small interfering RNA to ACSL1 expression and the CCK8 method was used to detect the drug sensitivity of cells to DTX.Results:In tissue samples from 292 cases of PCa,the proportion of M2-TAM was significantly higher than mostofother subtype.Module red revealed the most relevance with M2 tumor-associated macrophages.Functional annotation showed that biological processes and pathways were mainly related to myeloid leukocyte,osteoclast differentiation and the negative regulation of immune system process.Four hub genes were selected: ACSL1,DLGAPS,KIF23 and NCAPG.We found that after knocking down the expression of ACSL1,the sensitivity of prostate cancer cells to DTX increased significantly(P <0.05).Conclusion: In conclusion,bioinformatics analysis shows that M2-TAM is one of the main tumor infiltrating immune cells in PCa.Differential expressions of ACSL1,DLGAPS,KIF23,NCAPG may play an important driving force for M2-TAM infiltration.The identified hub genes facilitate our knowledge of the underlying molecular mechanism of how M2-TAM affect the drug resistance of DTX in PCa.Further validation showed that ACSL1 expression may be involved in the development of prostate cancer and the development of chemotherapy resistance,and it can be used as a potential target for tumor therapy.