Integrated multi-omics and experimental approaches identify fascin actin-bundling protein 1 as an unfavorable prognostic biomarker in adrenocortical carcinoma.

IF 3.3 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Pingkaiqi He, Yihao Chen, Ming Xi, Shanshan Mo, Jiahong Chen, Chuanfan Zhong, Fengping Liu, Weide Zhong, Le Zhang, Junhong Deng, Jianming Lu, Chao Cai
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Abstract

Adrenocortical carcinoma (ACC) is a rare epithelial tumor originating from adrenal cortical cells, notable for its high degree of malignancy and poor prognosis. Owing to heterogeneity, patient outcomes vary significantly. Current biomarkers for ACC risk stratification have notable limitations. However, with the advancement of multi-omics sequencing technology, we can utilize multi-omics data to explore the heterogeneity of ACC, thereby identifying novel biomarkers. In this study, we establish multicenter transcriptomics and ATAC-seq data from the TCGA and GEO databases to perform weighted gene coexpression network analysis (WGCNA) clustering and conduct comprehensive analyses of various ACC samples. These findings are integrated with univariate Cox regression, receiver operating characteristic (ROC) curve analysis, and survival analysis to identify potential biomarkers. We establish FSCN1 as an independent risk factor associated with poor ACC prognosis. ATAC-seq data demonstrate higher chromatin accessibility of FSCN1 in ACC patients with progressive disease. Immunohistochemical analysis confirms the expression of FSCN1 at the protein level, while functional cell assays reveal its role in promoting tumor invasion and proliferation. Functional enrichment analyses highlight the biological characteristics of FSCN1, and estimation of TME-infiltrating cells suggests that FSCN1 expression contributes to poor prognosis by inhibiting CD8 + T-cell infiltration within the ACC microenvironment. Finally, multi-omics analyses elucidate the role of FSCN1 at the mutation level. Taken together, our findings highlight FSCN1 as a promising novel biomarker and potential therapeutic target, underscoring its value in guiding the strategic management of ACC.

综合多组学和实验方法确定了筋膜蛋白肌动蛋白捆绑蛋白1是肾上腺皮质癌的不利预后生物标志物。
肾上腺皮质癌(Adrenocortical carcinoma, ACC)是一种起源于肾上腺皮质细胞的罕见上皮性肿瘤,其恶性程度高,预后差。由于异质性,患者的预后差异很大。目前用于ACC风险分层的生物标志物有明显的局限性。然而,随着多组学测序技术的进步,我们可以利用多组学数据来探索ACC的异质性,从而发现新的生物标志物。在本研究中,我们从TCGA和GEO数据库中建立多中心转录组学和ATAC-seq数据,对各种ACC样本进行加权基因共表达网络分析(WGCNA)聚类,并进行综合分析。这些发现与单变量Cox回归、受试者工作特征(ROC)曲线分析和生存分析相结合,以确定潜在的生物标志物。我们确定FSCN1是与ACC预后不良相关的独立危险因素。ATAC-seq数据显示,在ACC进行性疾病患者中,FSCN1的染色质可及性更高。免疫组化分析证实了FSCN1在蛋白水平上的表达,而功能细胞分析则揭示了其在促进肿瘤侵袭和增殖中的作用。功能富集分析强调了FSCN1的生物学特性,对tme浸润细胞的估计表明,FSCN1表达通过抑制ACC微环境中CD8 + t细胞的浸润而导致预后不良。最后,多组学分析阐明了FSCN1在突变水平上的作用。综上所述,我们的研究结果突出了FSCN1作为一种有前景的新型生物标志物和潜在的治疗靶点,强调了其在指导ACC战略管理方面的价值。
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来源期刊
Acta biochimica et biophysica Sinica
Acta biochimica et biophysica Sinica 生物-生化与分子生物学
CiteScore
5.00
自引率
5.40%
发文量
170
审稿时长
3 months
期刊介绍: Acta Biochimica et Biophysica Sinica (ABBS) is an internationally peer-reviewed journal sponsored by the Shanghai Institute of Biochemistry and Cell Biology (CAS). ABBS aims to publish original research articles and review articles in diverse fields of biochemical research including Protein Science, Nucleic Acids, Molecular Biology, Cell Biology, Biophysics, Immunology, and Signal Transduction, etc.
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