SOX11 as a potential prognostic biomarker in hepatocellular carcinoma linked to immune infiltration and ferroptosis.

IF 7 2区 医学 Q1 ONCOLOGY Chinese Journal of Cancer Research Pub Date : 2024-08-30 DOI:10.21147/j.issn.1000-9604.2024.04.03
Hongyu Chen, Qiangguo Ao, Yueling Wang, Yue Qian, Qingli Cheng, Wei Zhang
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Abstract

Objective: SOX11 is expressed in numerous malignancies, including hepatocellular carcinomas (HCC), but its oncogenic function has not been elucidated. Here, we performed a comprehensive bioinformatics analysis of the Liver Hepatocellular Carcinoma (LIHC) dataset to investigate the function of SOX11 in tumorgenesis.

Methods: SOX11 expression data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were validated by immunohistochemistry (IHC). Co-expression, differential expression, and functional analyses utilized TCGA-LIHC, Timer 2.0, Metascape, GTEx, and LinkedOmics databases. Associations with immune infiltration, ferroptosis, and immune checkpoint genes were assessed. Genetic changes were explored via CBioPortal. Logistic regression, receiver operating characteristic curve (ROC), Kaplan-Meier analysis, and nomogram modeling evaluated associations with HCC clinicopathological features. SOX11's impact on proliferation and migration was studied in HepG2 and HuH7 cell lines.

Results: SOX11 was significantly elevated in HCC tumors compared to controls. SOX11-associated genes exhibited differential expression in pathways involving extracellular membrane ion channels. Significant associations were found between SOX11 levels, immune infiltration, ferroptosis, and immune checkpoint genes in HCC tissue. SOX11 levels correlated with HCC stage, histologic grade, and tumor status, and independently predicted overall and disease-specific survival. SOX11 expression effectively distinguished between tumor and normal liver tissue. Spearman correlations highlighted a significant relationship between SOX11 and ferroptosis-associated genes. Decreased SOX11 levels in HepG2 and HuH7 cells resulted in reduced proliferation and migration.

Conclusions: SOX11 was found to represent a promising biomarker within HCC diagnosis and prognosis together with being a possible drug-target.

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SOX11作为肝细胞癌潜在的预后生物标志物与免疫浸润和铁变态反应有关。
目的:SOX11在包括肝细胞癌(HCC)在内的多种恶性肿瘤中均有表达,但其致癌功能尚未阐明。在此,我们对肝细胞癌(LIHC)数据集进行了全面的生物信息学分析,以研究SOX11在肿瘤发生中的功能:通过免疫组化(IHC)验证了癌症基因组图谱(TCGA)和基因表达总库(GEO)中的SOX11表达数据。共表达、差异表达和功能分析利用了TCGA-LIHC、Timer 2.0、Metascape、GTEx和LinkedOmics数据库。评估了与免疫浸润、铁突变和免疫检查点基因的关联。通过 CBioPortal 对基因变化进行了研究。逻辑回归、接收者操作特征曲线(ROC)、Kaplan-Meier分析和提名图模型评估了与HCC临床病理特征的关联。在 HepG2 和 HuH7 细胞系中研究了 SOX11 对增殖和迁移的影响:结果:与对照组相比,SOX11在HCC肿瘤中明显升高。SOX11相关基因在涉及细胞外膜离子通道的通路中表现出不同的表达。在 HCC 组织中,SOX11 水平、免疫浸润、铁变态反应和免疫检查点基因之间存在显著关联。SOX11水平与HCC分期、组织学分级和肿瘤状态相关,并能独立预测总生存期和疾病特异性生存期。SOX11 的表达能有效区分肿瘤和正常肝组织。斯皮尔曼相关性强调了SOX11与铁蛋白沉积相关基因之间的重要关系。HepG2和HuH7细胞中SOX11水平的降低导致增殖和迁移能力下降:结论:研究发现 SOX11 是诊断 HCC 和预后的一种有前途的生物标记物,同时也是一种可能的药物靶点。
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来源期刊
自引率
9.80%
发文量
1726
审稿时长
4.5 months
期刊介绍: Chinese Journal of Cancer Research (CJCR; Print ISSN: 1000-9604; Online ISSN:1993-0631) is published by AME Publishing Company in association with Chinese Anti-Cancer Association.It was launched in March 1995 as a quarterly publication and is now published bi-monthly since February 2013. CJCR is published bi-monthly in English, and is an international journal devoted to the life sciences and medical sciences. It publishes peer-reviewed original articles of basic investigations and clinical observations, reviews and brief communications providing a forum for the recent experimental and clinical advances in cancer research. This journal is indexed in Science Citation Index Expanded (SCIE), PubMed/PubMed Central (PMC), Scopus, SciSearch, Chemistry Abstracts (CA), the Excerpta Medica/EMBASE, Chinainfo, CNKI, CSCI, etc.
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