Pan-Cancer Analysis Predicts FOXS1 as a Key Target in Prognosis and Tumor Immunotherapy

Abstract

Purpose Only a few studies have reported the role of FOXS1, a transcriptional factor, in the tumor development process. In this article, we investigate the function of FOXS1 in distinct neoplastic development and the tumor immune microenvironment (TIME). Patients and Methods The latent roles of FOXS1 in various tumors were prospected based on TCGA, GTEx, CCLE, GEPIA2, cBioPortal, TIMER, ImmuCellAI databases, GSVA datasets, GSEA datasets, and R packages. The expression difference, gene alteration, clinical characteristics, prognostic values, biological mechanism, potential pathways, tumor microenvironment, and immune cell infiltration related to FOXS1 were appraised. Results FOXS1 was strongly expressed in pan-cancer, and this gene was associated with low survival rates. FOXS1 was linked to many pathways that are cancer-promoting and immune-related. The expression of this transcriptional factor in cancers was positively related to immune cell infiltration, especially M2-like macrophages and Treg cells. In addition to that, FOXS1 demonstrated a positive relationship with many immune-suppression genes, such as TGFB1 and ARORA2A . Conclusion Our study identified an oncogenic effect of FOXS1, which may play a vital role as a prognosticative biological marker in pan-cancer. Exorbitant expression of FOXS1 is associated with high TAMs and Treg cells infiltration. These cells have an immunosuppressive function and promote the development of the immunosuppressive tumor microenvironment. The research of FOXS1 provided a potential drug target for tumor immunotherapy.

Pan‐cancer analyses reveal multi‐omic signatures and clinical implementations of the forkhead‐box gene family

“…Our study reveals the full omics picture of the FOX gene family and its clinical implications, including survival prediction value and possible therapeutic targets, by conducting an integrated analysis covering multi‐omics and clinical data of the FOX gene family from over 11,000 pan‐cancer patients. In agreement with previous reports in a single FOX gene, 18,19 heterogeneity of FOX gene expression across cancer types was found in our results, and it was partially contributed by genomic or epigenomic changes. Additionally, we discovered previously unreported heterogeneous expression pattern and skewed cancer‐type genomic alteration pattern among the FOX gene family members.…”

“…To date, a limited number of studies have been conducted to investigate the transcriptomic/epigenomic alterations of FOX genes from a multi‐cancer perspective 18–20 . However, the overall picture of the FOX gene family across human cancers is largely elusive due to the studies mainly focused on a single FOX gene or particular molecular data types.…”

Differential regulation of TNFα and IL-6 expression contributes to immune evasion in prostate cancer

“…8 ) and expressed higher levels of ARG1 and FOXS1 which are both associated with M2 macrophage polarization (Fig. 9 ) [ 35 – 38 ].…”

A novel inflammatory response-related signature predicts the prognosis of skin cutaneous melanoma and the effect of anti-tumor drugs

“…The ESTIMATE algorithm in the R language ESTIMATE package was used to estimate the rate of the immune stromal component in TME for each sample, which is reported as three scores: stemnessScore, immuneScore, and stromalScore. Additionally, we employed computational approaches such as ESTIMATE [23], TIMER [24] , MCPcounter [25] , CIBERSORTx [26] , and ssGSEA in the training group to synthesize immunological differences in the risk model using the R language's pheatmap package to visualize the graphs.…”