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Diaphanous-related formin subfamily: Novel prognostic biomarkers and tumor microenvironment regulators for pancreatic adenocarcinoma.

ABSTRACT: The diaphanous-related formin subfamily includes diaphanous homolog 1 (DIAPH1), DIAPH2, and DIAPH3. DIAPHs play a role in the regulation of actin nucleation and polymerization and in microtubule stability. DIAPH3 also regulates the assembly and bipolarity of mitotic spindles. Accumulating evidence has shown that DIAPHs are anomalously regulated during malignancy. In this study, we reviewed The Cancer Genome Atlas database and found that DIAPHs are abundantly expressed in pancreatic adenocarcinoma (PAAD). Furthermore, we analyzed the gene alteration profiles, protein expression, prognosis, and immune reactivity of DIAPHs in PAAD using data from several well-established databases. In addition, we conducted gene set enrichment analysis to investigate the potential mechanisms underlying the roles of DIAPHs in the carcinogenesis of PAAD. Finally, we performed the experimental validation of DIAPHs expression in several pancreatic cancer cell lines and tissues of patients. This study demonstrated significant correlations between DIAPHs expression and clinical prognosis, oncogenic signature gene sets, T helper 2 cell infiltration, plasmacytoid dendritic cell infiltration, myeloid-derived suppressor cell infiltration, ImmunoScore, and immune checkpoints in PAAD. These data may provide important information regarding the role and mechanisms of DIAPHs in tumorigenesis and PAAD immunotherapy.

SUBMITTER: Zhang B

PROVIDER: S-EPMC9797685 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Diaphanous-related formin subfamily: Novel prognostic biomarkers and tumor microenvironment regulators for pancreatic adenocarcinoma.

Zhang Bixi B Hu Qing Q Li Yanchun Y Xu Canxia C Xie Xiaoran X Liu Peng P Xu Meihua M Gong Siming S Wu Hao H

Frontiers in molecular biosciences 20221215

The diaphanous-related formin subfamily includes diaphanous homolog 1 (DIAPH1), DIAPH2, and DIAPH3. DIAPHs play a role in the regulation of actin nucleation and polymerization and in microtubule stability. DIAPH3 also regulates the assembly and bipolarity of mitotic spindles. Accumulating evidence has shown that DIAPHs are anomalously regulated during malignancy. In this study, we reviewed The Cancer Genome Atlas database and found that DIAPHs are abundantly expressed in pancreatic adenocarcinom ...[more]

PMID: 36589226

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Project description:BackgroundTumor microenvironment (TME) plays an essential role in lung adenocarcinoma (LUAD) development and metastasis. With the development of TME research, it has been proved that differences in tumor-infiltrating immune cells (TICs) and gene expression profile are related to the prognosis of cancer. The aim of our study was to identify key genes affecting immune state in TME of LUAD.MethodsThe RNA-seq data and clinical characteristics of 594 LUAD patients were downloaded from the TCGA database. ImmuneScore, StromalScore and ESTIMATEScore of each LUAD sample were calculated using ESTIMATE algorithm. Based on the median of different scores, LUAD samples were divided into high and low score groups. Differentially expressed genes (DEGs) between groups were obtained, and univariate Cox regression analysis and protein-protein interaction (PPI) network were used to screen the shared DEGs generating in the intersection analysis. Finally, the CIBORSORT algorithm was performed to calculate the relative contents of TICs for each LUAD sample, and the correlation analysis between TICs and key genes was used to determine the influence of key genes to the TME.ResultsIn the presented study, we found that three different scores were positively correlated with the prognosis of LUAD patients, and correlation analysis showed the different scores were closely related to tumor progression and metastasis. After performing the intersection analysis, a total of 585 up-regulated and 107 down-regulated DEGs between the high and low score groups were obtained, all of which were enriched in immune-related functions. Having used univariate COX regression analysis and PPI network, the key genes, CCR2 and PTPRC, affecting the immune status of TME and the prognosis of LUAD were acquired. Analysis based on the CIBERSORT algorithm suggested that CCR2 and PTPRC were correlated with a variety of TICs, and closely related to the clinical characteristics of the LUAD patients.ConclusionsOur research showed that CCR2 and PTPRC may be potential prognostic markers in LUAD, which may affect the function of γδT cells and other immune cells by participating in the regulation of TME immune state.

Dataset Information

Diaphanous-related formin subfamily: Novel prognostic biomarkers and tumor microenvironment regulators for pancreatic adenocarcinoma.

Publications

Diaphanous-related formin subfamily: Novel prognostic biomarkers and tumor microenvironment regulators for pancreatic adenocarcinoma.

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