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单细胞与批量RNA测序的综合分析揭示HSD3B7作为ccRCC的预后生物标志物和潜在治疗靶点

Integrated Analysis of Single-Cell and Bulk RNA Sequencing Reveals HSD3B7 as a Prognostic Biomarker and Potential Therapeutic Target in ccRCC.

作者信息

Liu Guicen, Liu Qichen, Zhao Jiawei, Luo Ruyue, Wan Yuan, Luo Zhongli

机构信息

Molecular Medicine and Cancer Research Center, School of Basic Medical Science, Chongqing Medical University, 400016 Chongqing, China.

College of Paediatrics, Chongqing Medical University, 400016 Chongqing, China.

出版信息

Int J Mol Sci. 2024 Dec 1;25(23):12929. doi: 10.3390/ijms252312929.

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common kidney malignancy, with a poor prognosis for advanced-stage patients. Identifying key biomarkers involved in tumor progression is crucial for improving treatment outcomes. In this study, we employed an integrated approach combining single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (bulk RNA-seq) to identify biomarkers associated with ccRCC progression and prognosis. Single-cell transcriptomic data were obtained from publicly available datasets, and genes related to tumor progression were screened using Monocle2. Bulk RNA-seq data for ccRCC were retrieved from The Cancer Genome Atlas (TCGA) and integrated with scRNA-seq data to explore tumor heterogeneity. We identified 3 beta-hydroxy steroid dehydrogenase type 7 (HSD3B7) as a candidate biomarker for ccRCC, associated with poor overall survival, disease-specific survival, and progression-free interval. Elevated HSD3B7 expression correlated with aggressive clinical features such as advanced TNM stages, histologic grades, and metastasis. Functional studies demonstrated that HSD3B7 promotes cell proliferation, migration, and invasion in vitro, while its silencing significantly inhibits tumor growth in vivo. Our findings reveal that HSD3B7 is a novel biomarker for ccRCC, providing insights into its role in tumor progression and potential as a target for therapy. This study highlights the value of integrating scRNA-seq and bulk RNA-seq data to uncover key regulators of tumor biology and lays the foundation for developing personalized therapeutic strategies for ccRCC patients.

摘要

透明细胞肾细胞癌(ccRCC)是最常见的肾脏恶性肿瘤,晚期患者预后较差。识别参与肿瘤进展的关键生物标志物对于改善治疗效果至关重要。在本研究中,我们采用了一种将单细胞RNA测序(scRNA-seq)和批量RNA测序(bulk RNA-seq)相结合的综合方法,以识别与ccRCC进展和预后相关的生物标志物。单细胞转录组数据从公开可用的数据集中获得,并使用Monocle2筛选与肿瘤进展相关的基因。ccRCC的批量RNA-seq数据从癌症基因组图谱(TCGA)中检索,并与scRNA-seq数据整合以探索肿瘤异质性。我们确定3β-羟基类固醇脱氢酶7型(HSD3B7)为ccRCC的候选生物标志物,与总体生存期、疾病特异性生存期和无进展生存期较差相关。HSD3B7表达升高与侵袭性临床特征相关,如晚期TNM分期、组织学分级和转移。功能研究表明,HSD3B7在体外促进细胞增殖、迁移和侵袭,而其沉默在体内显著抑制肿瘤生长。我们的研究结果表明,HSD3B7是ccRCC的一种新型生物标志物,为其在肿瘤进展中的作用及作为治疗靶点的潜力提供了见解。本研究强调了整合scRNA-seq和批量RNA-seq数据以揭示肿瘤生物学关键调节因子的价值,并为开发ccRCC患者的个性化治疗策略奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9cd/11641532/18be5ea91f42/ijms-25-12929-g001.jpg

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