ARHGAP44 gene: a cytoskeleton mobility-related modulator with implications in pan-cancer prognostic risk and immune regulation

Introduction: Rho GTPases have been a well-known family of small G proteins that regulate cellular cytoskeleton dynamics and are involved in multiple critical steps of cancer progression. However, ARHGAP44 gene, a member of GAP proteins that regulate the Rho GTPases cycling between their active GTP-bound and inactive GDP-bound states, remains poorly understood in terms of its role in cancer development. This study aims to analyze the functions of ARHGAP44 gene in a broad spectrum of human cancers, thus aiding in the better understanding of the collaborative network of cytoskeleton-related genes in cancers. Methods: The study 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 a broad spectrum of human cancers. Furthermore, the probable reasons for the aberrant changed expression of ARHGAP44 in cancers compared to corresponding normal control samples were investigated. Moreover, the correlation of ARHGAP44 with multiple critical clinical cancer parameters was performed in succession. Results: The basic genetic physicochemical properties of ARHGAP44 including its amino-acid composition, estimated molecular weight, and protein half-life were investigated. Then, genetic alteration analysis revealed that ARHGAP44 expression varies in human cancers, which was partly due to the modulation by DNA methylation and phosphorylation. Furthermore, ARHGAP44 gene was 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 associated with the sensitivity of several chemotherapy-related drugs. Conclusions: Based on multiple analyses, some valuable strategies to guide the therapeutic orientation concerning the role of ARHGAP44 gene in human cancers were revealed, although more detailed experiments and clinical trials are obligatory to support further clinical medical applications of the gene, especially in each independent cancer type.