Role of ARRB1 in prognosis and immunotherapy: A Pan-Cancer analysis

Abstract

Background: β-arrestin1 (ARRB1), was originally identified as a multifunctional adaptor protein. Although ARRB1 has recently been shown to also play an important role in tumor growth, metastasis, inflammation, and immunity, its relationship with distinct tumor types and the tumor immune microenvironment remains unclear.Methods: We analyzed the ARRB1 expression profile and clinical characteristics in 33 cancer types using datasets from The Cancer Genome Atlas (TCGA) database. Clinical parameters such as patient survival, tumor stage, age, and gender were used to assess the prognostic value of ARRB1. The Human Protein Atlas (HPA) database was used to explore ARRB1 protein expression data. ESTIMATE and CIBERSORT algorithms were performed to assess immune infiltration. Furthermore, putative correlations between ARRB1 and tumor-infiltrating immune cells, the signatures of T-cell subtypes, immunomodulators, the tumor mutation burden (TMB), Programmed cell death ligand 1 (PD-L1), and microsatellite instability (MSI) were also explored. Gene functional enrichment was determined using GSEA. GSE40435 and GSE13213 cohorts were used to validate the correlation of ARRB1 with KIRC and LUAD clinicopathological parameters. Finally, the relationship between ARRB1 and immunotherapeutic responses was assessed using three independent immunotherapy cohorts, namely, GSE67501, GSE168204, and IMvigor210.Results: We found that ARRB1 expression levels were lower in 17 tumor tissues than in the corresponding normal tissues. We further found that ARRB1 expression was significantly correlated with tumor stage in BRCA, ESCA, KIRC, TGCT, and THCA, while in some tumors, particularly KIRC and LUAD, ARRB1 expression was associated with better prognosis. ARRB1 expression was also positively correlated with the stromal score or the immune score in some tumors. Regarding immune cell infiltration, ARRB1 expression in DLBC was positively correlated with M1 macrophage content and negatively correlated with B-cell infiltration. Additionally, there was a broad correlation between ARRB1 expression and three classes of immunomodulators. Furthermore, high ARRB1 expression levels were significantly correlated with some tumor immune-related pathways. Finally, ARRB1 expression was significantly associated with MSI, PD-L1, and TMB in some tumors and with the efficacy of immune checkpoint inhibitors (ICIs) in melanoma.Conclusion: ARRB1 has prognostic value in malignant tumors, especially in KIRC and LUAD. At the same time, ARRB1 was closely correlated with the tumor immune microenvironment and indicators of immunotherapy efficacy, indicating its great potential as a reliable marker for predicting the efficacy of immunotherapy.

CHMP4C as a novel marker regulates prostate cancer progression through cycle pathways and contributes to immunotherapy

“…In the clinical prediction of different treatment regimens for prostate cancer anti-PD1 and anti-CTLA4, the low CHMP4C expression group always showed better response compared to the high CHMP4C expression group. GSE67501 has been used as an independent cohort for immunotherapy (PD-1/PD-L1) to predict the value of target genes in immunotherapy ( 40 ) ( 41 ). In the GSE67501 cohort, the low expression CHMP4C group was also more sensitive to immunotherapy, which is consistent with our findings.…”

Identification of Proteins and Genes Associated with Hedgehog Signaling Pathway Involved in Neoplasm Formation Using Text-Mining Approach

“…They revealed that Rest1 antagonizes Gli1 by regulating Arrb1 which is an inhibitor of Gli1. Also, Arrb1 is associated with gastric cancer: it was shown that a knockdown of the Arrb1 gene led to impaired cell proliferation [98] . Unidirectional changes in the expression of the Arrb1 gene may lead to divergent prognoses in different types of cancer [99] .…”

Targeted therapies in bladder cancer: signaling pathways, applications, and challenges

“…ARRB was initially identified as a multifunctional adaptor protein that plays a key role in tumor growth, metastasis, inflammation, and immunity 236 . ARRBs regulate stem cell markers and BC characteristics.…”

“…ARRB was initially identified as a multifunctional adaptor protein that plays a key role in tumor growth, metastasis, inflammation, and immunity. 236 ARRBs regulate stem cell markers and BC characteristics. ARRB1 and ARRB2 possess contradictory functions in regulating the stem cell characteristics of BC.…”