FLG Gene Mutation Up-regulates the Abnormal Tumor Immune Response and Promotes the Progression of Prostate Cancer

Abstract

Background: Prostate Cancer (PCa) ranks sixth with regard to the cause of cancerinduced male diseases worldwide, and inflammation is closely associated with its morbidity, deterioration, and prognosis. Tumor Mutation Burden (TMB) is identified to be the most common biomarker for the prediction of immunotherapy. But it is still unclear about the relationship of gene mutations in PCa with TMB and immune response.

Objectives: To study the relationship between gene mutation and anti-tumor immune response in the prostate cancer tumor microenvironment.

Methods: In the present work, the PCa somatic mutation data were collected from the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) datasets.

Results: As a result, 8 genes with high mutation frequency, including TP53, PTEN, TTN, FLG, CTNNB1, SPOP, MUC16, and KMT2C, were discovered to be covered by 4 cohorts from the United States, Canada, the United Kingdom, and China. Overall, the FLG mutation was related to a greater TMB, which predicted the dismal prognostic outcome. Besides, the CIBERSORT algorithm and Gene Set Enrichment Analysis (GSEA) were adopted for analysis, which revealed that FLG mutation remarkably promoted immune response in the context of PCa and accelerated cancer development. To sum up, FLG shows a high mutation frequency in PCa, and is related to the increase in TMB, up-regulation of abnormal immune responses in tumors, and promotion of tumor progression.

Conclusion: Therefore, it may be used as a biomarker to predict the abnormal immune responses and provide a therapeutic target for immunotherapy in the treatment of PCa.

Keywords: FLG; ICGC; TCGA; cibersort; prostate cancer; tumor immunity; tumor infiltrating immune cells; tumor mutation burden.