Abstract
BackgroundStromal components of the tumor microenvironment contribute to bladder cancer progression, and Cancer-Associated Fibroblasts (CAFs) were reported to play an important role. Accumulating pieces of evidence indicate that CAFs participate in the crosstalk with tumor cells and have a complex interaction network with immune components. Further studies on the role of CAFs in the bladder cancer microenvironment and searching for possible specific markers are important for a deeper understanding of CAFs in bladder cancer progression and immunomodulation.MethodsIn the present study, we examined the abundance of CAFs in the TCGA and GEO datasets using the MCP-COUNTER algorithm. Additionally, the expression of genes related to CAFs was analyzed through the Weighted Gene Co-expression Network Analysis (WGCNA). The CIBERSORT and ESTIMATE algorithms were used to discuss the correlation of the key CAFs-related gene and the tumor microenvironment components. Immunohistochemistry analysis in clinical samples was used to validate the results of bioinformatics analysis.ResultsThe results showed that CAFs were closely associated with the progression and prognosis of bladder cancer. WGCNA also revealed that CALD1 was a key CAFs-related gene in bladder cancer. Moreover, further in-depth analysis showed that CALD1 significantly affected the progression and prognosis of bladder cancer. The CIBERSORT and ESTIMATE algorithms demonstrated significant correlations between CALD1 and the tumor microenvironment components, including CAFs, macrophages, T cells, and multiple immune checkpoint related genes. Finally, immunohistochemistry results validated the strong association of CALD1 with CAFs and macrophages.ConclusionsIn the present study, we confirmed the cancer-promoting roles of CAFs in bladder cancer. Being a key gene associated with CAFs, CALD1 may promote bladder cancer progression by remodeling the tumor microenvironment. The bioinformatics methods, including the CIBERSORT, MCP-COUNTER and ESTIMATE algorithms, may provide important value for studying the tumor microenvironment.
Highlights
Bladder Cancer (BLCA) is one of the most common malignant tumors of the genitourinary system [1]
Being a key gene associated with Cancer-Associated Fibroblasts (CAFs), Caldesmon 1 (CALD1) may promote bladder cancer progression by remodeling the tumor microenvironment
Abundance of CAFs is a poor prognostic factor associated with the progression of BLCA We first calculated the abundance of CAFs in the The Cancer Genome Atlas (TCGA) cohort using the MCP-COUNTER algorithm
Summary
Bladder Cancer (BLCA) is one of the most common malignant tumors of the genitourinary system [1]. Intravesical instillation of Bacillus Calmette-Guerin (BCG) was first reported to be effective in treating NMIBC by Morales et al in 1976, with complete remission rates up to 70−80 % [3]. This was the earliest application of immunotherapy for the management of BLCA and has been used up to date. BLCA represents a growing number of cancers characterized by the infiltration of a significant number of immune cells in the tumor microenvironment (TME) [4, 5], making it suitable for immunotherapy. Stromal components of the tumor microenvironment contribute to bladder cancer progression, and Cancer-Associated Fibroblasts (CAFs) were reported to play an important role. Further studies on the role of CAFs in the bladder cancer microenvironment and searching for possible specific markers are important for a deeper understanding of CAFs in bladder cancer progression and immunomodulation
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