Identification of HOXC Gene Family as Prognostic and Immune-Related Biomarkers in Breast Cancer Through mRNA Transcriptional Profile and Experimental Validation.

IF 2.1 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemical Genetics Pub Date : 2024-07-12 DOI:10.1007/s10528-024-10884-5
Xiongtao Cheng, Jie Luo, Jianxiong Cao
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Abstract

Breast cancer (BC) is the most common malignancy in women worldwide, and more effective biomarkers are urgently needed for the prevention and treatment of BC. Our study aimed to investigate the role of the HOXC gene family (HOXCs) and its relationship with the immune response in BC. The differential expression of HOXCs and its clinical prognostic significance in BC were explored using bioinformatics analysis, and the cBioPortal database was used to evaluate the genetic mutation profile of the HOXCs in BC. The results indicated that the expression levels of HOXC4, 10, 11, 12, and 13 were significantly increased in BC tissues compared with the normal tissues, and expressions of these genes were closely associated with BC stage, among them, high expression levels of HOXC10 and HOXC13 predicted poor outcome in BC patients. In addition, to elucidate the essential role of HOXCs in the tumor microenvironment and immunotherapeutic response of BC, the impact of HOXCs on the regulation of immune infiltration in BC was comprehensively assessed. The result showed that HOXC10 and HOXC13 expressions were significantly positively linked with the infiltration levels of CD8+T cell and M1 macrophage, while they were negatively related to Mast and Natural killer cells, suggesting the important influence of HOXCs on regulating tumor immunity in BC patients. Lastly, the RT-qPCR assay was employed to validate HOXCs expression in samples of BC patients. In conclusion, HOXCs may be a promising prognostic indicator and could regulate the immune infiltration in BC patients, thus being a promising targeted immunotherapy for BC.

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通过 mRNA 转录谱和实验验证鉴定作为乳腺癌预后和免疫相关生物标志物的 HOXC 基因家族
乳腺癌(BC)是全球女性最常见的恶性肿瘤,预防和治疗BC急需更有效的生物标志物。我们的研究旨在探讨HOXC基因家族(HOXCs)在乳腺癌中的作用及其与免疫反应的关系。通过生物信息学分析探讨了HOXCs在BC中的差异表达及其临床预后意义,并利用cBioPortal数据库评估了BC中HOXCs的基因突变情况。结果表明,与正常组织相比,HOXC4、10、11、12和13在BC组织中的表达水平明显升高,且这些基因的表达与BC分期密切相关,其中HOXC10和HOXC13的高表达水平预示着BC患者的不良预后。此外,为了阐明HOXCs在BC肿瘤微环境和免疫治疗反应中的重要作用,研究人员全面评估了HOXCs对BC免疫浸润调控的影响。结果显示,HOXC10和HOXC13的表达与CD8+T细胞和M1巨噬细胞的浸润水平呈显著正相关,而与Mast细胞和自然杀伤细胞呈显著负相关,提示HOXCs对调控BC患者肿瘤免疫具有重要影响。最后,采用RT-qPCR方法验证了HOXCs在BC患者样本中的表达。总之,HOXCs可能是一个很有前景的预后指标,并能调节BC患者的免疫浸润,因此是一种很有前景的BC靶向免疫疗法。
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来源期刊
Biochemical Genetics
Biochemical Genetics 生物-生化与分子生物学
CiteScore
3.90
自引率
0.00%
发文量
133
审稿时长
4.8 months
期刊介绍: Biochemical Genetics welcomes original manuscripts that address and test clear scientific hypotheses, are directed to a broad scientific audience, and clearly contribute to the advancement of the field through the use of sound sampling or experimental design, reliable analytical methodologies and robust statistical analyses. Although studies focusing on particular regions and target organisms are welcome, it is not the journal’s goal to publish essentially descriptive studies that provide results with narrow applicability, or are based on very small samples or pseudoreplication. Rather, Biochemical Genetics welcomes review articles that go beyond summarizing previous publications and create added value through the systematic analysis and critique of the current state of knowledge or by conducting meta-analyses. Methodological articles are also within the scope of Biological Genetics, particularly when new laboratory techniques or computational approaches are fully described and thoroughly compared with the existing benchmark methods. Biochemical Genetics welcomes articles on the following topics: Genomics; Proteomics; Population genetics; Phylogenetics; Metagenomics; Microbial genetics; Genetics and evolution of wild and cultivated plants; Animal genetics and evolution; Human genetics and evolution; Genetic disorders; Genetic markers of diseases; Gene technology and therapy; Experimental and analytical methods; Statistical and computational methods.
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