AKAP7 is a prognostic biomarker involved in immune infiltration of bladder urothelial carcinoma and correlated with ferroptosis

AKAP7是一种预后生物标志物,参与膀胱尿路上皮癌的免疫浸润,并与铁死亡相关。

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Abstract

BACKGROUND: Bladder urothelial carcinoma (BLCA) is a common urinary malignancy, and the identification of appropriate biomarkers remains a significant challenge. AKAP7 is a molecular scaffolding protein that plays a crucial role in spatially regulating cyclic adenosine monophosphate (cAMP) signaling through its ability to anchor protein kinase A (PKA) to the cytoskeleton. This study aims to explore the expression level, prognostic implications and immune characteristics of AKAP7 in BLCA. METHODS: Based on numerous databases, including CCLE, HPA, Harmonizome, TCGA, GEO, GEPIA2, Kaplan-Meier plotters, GENT2, cBioPortal and the COSMIC databases, we explored the expression pattern, prognostic value and gene alteration and mutation of AKAP7. The potential molecular mechanisms of AKAP7 were analyzed via the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Furthermore, using single-cell RNA-seq datasets, we investigated the distribution of AKAP7 in tumor microenvironments (TME). We utilized the TISIDB database to analyze the association between AKAP7 and immune characteristics. Additionally, we explored the correlation between AKAP7 expression and ferroptosis using TCGA and GEO data sets. Finally, we verified the expression level of AKAP7 in clinical samples of BLCA as well as BLCA cell lines. RESULTS: Compared with normal tissues, we observed a decreased expression level of AKAP7 in BLCA tissues. BLCA patients with low AKAP7 expression showed poor prognosis. The expression of AKAP7 had a significant positive correlation with the infiltration of T helper cells, Tcm, Eosinopoils, TFH, Th17 and CD8 T cells. The TCGA and GEO datasets suggested that the expression of AKAP7 was closely associated with a ferroptosis-related gene Acyl-CoA synthetase long-chain family member 4 (ACSL4). CONCLUSION: AKAP7 may play a critical role in the prognosis and immune regulation of BLCA prognosis. Besides, it is related to ferroptosis. AKAP7 is an effective biomarker in BLCA.

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