关键词: Breast cancer DAAM2 Liver cancer Lower grade glioma Prognostic value

Mesh : Humans Female Breast Neoplasms / genetics Prognosis Liver Neoplasms / genetics Carcinoma, Hepatocellular / genetics Glioma Morphogenesis Microfilament Proteins rho GTP-Binding Proteins

来  源:   DOI:10.1007/s12094-023-03111-x

Abstract:
OBJECTIVE: Dishevelled-associated activator of morphogenesis 2 (DAAM2) is a formin protein and has a potential role in the tumor metastasis. The prognostic value of DAAM2 in pan-cancer is investigated in this study.
METHODS: TCGA and GTEx database were downloaded to perform bioinformatics analysis and ROC curves. Then we explored protein-protein interaction and GO-KEGG enrichment to figure out the protein pathways associated with DAAM2 and studied DAAM2-related immune infiltration and methylation. Fifteen pairs of BRCA clinical samples were enrolled to determine the expression and distribution of DAAM2 in BRCA sections by immunohistochemistry. Finally, BRCA cells were transfected with siRNA targeting DAAM2 and subsequently subject to cell proliferation, migration, and invasion assays.
RESULTS: DAAM2 was closely related to the diagnosis and clinical characteristics of lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), and breast cancer (BRCA). Survival curve analysis demonstrated DAAM2 served as a potential prognostic indicator of LGG and LIHC (P = 0.0029 and P = 0.025, respectively). DAAM2 was mainly participated in signaling pathways mediating cytoskeleton regulation and tumor development. The correlation of DAAM2 with tumor-infiltrating immune cells (TIICs) and methylation levels was conducive to the prediction of novel biomarkers of pan-carcinoma. DAAM2 was highly expressed in BRCA tissues than that in paracancerous tissues. The proliferation, invasion, and migration of BRCA cells were inhibited by DAAM2 siRNA.
CONCLUSIONS: DAAM2 had a specific value in foretelling the prognosis of LGG, LIHC, and BRCA. High expression level of DAAM2 has longer survival rates in LGG and LIHC. The knockdown of DAAM2 retards the proliferation, invasion, and migration of BRCA cells. This study provides a novel sight of DAAM2 into the exploration of a potential biomarker in pan-cancer.
摘要:
目的:形态发生相关激活因子2(DAAM2)是一种形式蛋白,在肿瘤转移中具有潜在作用。这项研究调查了DAAM2在泛癌症中的预后价值。
方法:下载TCGA和GTEx数据库进行生物信息学分析和ROC曲线。然后,我们探索了蛋白质-蛋白质相互作用和GO-KEGG富集,以找出与DAAM2相关的蛋白质途径,并研究了DAAM2相关的免疫浸润和甲基化。纳入15对BRCA临床样本,通过免疫组织化学确定DAAM2在BRCA切片中的表达和分布。最后,用靶向DAAM2的siRNA转染BRCA细胞,随后进行细胞增殖,迁移,和入侵检测。
结果:DAAM2与低级别胶质瘤(LGG)的诊断和临床特征密切相关,肝细胞癌(LIHC),乳腺癌(BRCA)。生存曲线分析表明DAAM2是LGG和LIHC的潜在预后指标(分别为P=0.0029和P=0.025)。DAAM2主要参与介导细胞骨架调控和肿瘤发生发展的信号通路。DAAM2与肿瘤浸润免疫细胞(TIIC)和甲基化水平的相关性有助于预测泛癌的新型生物标志物。DAAM2在BRCA组织中比癌旁组织高表达。扩散,入侵,DAAM2siRNA抑制BRCA细胞的迁移。
结论:DAAM2在预测LGG的预后方面具有特定的价值,LIHC,BRCA。DAAM2的高表达水平在LGG和LIHC中具有更长的存活率。DAAM2的击倒延缓了扩散,入侵,和BRCA细胞的迁移。这项研究为DAAM2探索泛癌症中潜在的生物标志物提供了新的视角。
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