Pan-cancer Analysis of a Cytoskeleton Mobility related ARHGAP44 gene with Potential Implications in Cancer Prognosis Risk Prediction and Immune Landscape Modulation

Abstract Background Rho GTPases has been a well known family of small G proteins that regulate cellular cytoskeleton dynamics and involve in multiple critical steps of cancer progression. However, ARHGAP44 gene which is a member of GAP proteins that regulates the Rho GTPases cycling between their active GTP-bound and inactive GDP-bound state, its role in cancer development is still lack of understanding. The study is to analyze the function of ARHGAP44 gene in broad spectrum human cancers, thus aiding better understanding of the collaborative network of cytoskeleton related genes in cancers. Methods In the study, we started with the analysis of the genetic characteristics of ARHGAP44 gene, followed by its expression patterns, frequent alterations as well as survival prediction value in broad spectrum human cancers. Further, the probable reasons for the aberrant changed expression of ARHGAP44 in cancers comparing to corresponding normal control samples were investigated. Moreover, the correlation of ARHGAP44 with multiple critical clinical cancer parameters were in succession performed. Results Firstly, basic genetic physicochemical properties of ARHGAP44 were investigated including its aminoacid composition, estimated molecular weight and protein half life. Then, genetic alteration analysis revealed that ARHGAP44 expression various in human cancers, which was partly due to the modulation by DNA methylation and phosphorylation. Further, ARHGAP44 gene was indicated to be associated with multiple critical cancer traits including cancer stemness, cytoskeleton dynamics as well as immune infiltration in different human cancer types. Moreover, ARHGAP44 gene was also supported to be associated with the sensitivity of several chemotherapy related drugs. Conclusions Based on multiple bioinformatic analysis and TCGA pan-cancer data as well as certain local hospital samples, we revealed some valuable strategies to guide the therapeutic orientation concerning the role of ARHGAP44 gene in human cancers, although more detailed experiments and clinical trials are obligatory to support further clinical medical application of the gene, especially in each type of independent cancer.