HGH1 在乳腺癌预后中的作用：一项关于免疫反应和细胞周期的研究

IF 3.4 2区医学 Q2 ONCOLOGY

BMC Cancer Pub Date : 2024-09-09 DOI:10.1186/s12885-024-12879-2

Hailong Li, Yong Xu, Rong Xu, Wei Du

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引用次数: 0

摘要

乳腺癌（BRCA）仍然是全球妇女死于癌症的主要原因之一。据报道，HGH1 同源物（HGH1）与肿瘤免疫有关。然而，HGH1 在 BRCA 中的功能仍不清楚。因此，本研究探讨了HGH1在BRCA中的潜在作用。研究人员利用癌症基因组图谱（TCGA）数据库和基因表达总库（GEO）获得了BRCA的RNA-seq数据。利用人类蛋白质图谱（HPA）确定了HGH1的蛋白质定位，免疫组织化学（IHC）染色显示HGH1在临床BRCA组织中表达上调。利用异种移植小鼠检测肿瘤生长和乳腺癌细胞中HGH1的表达。利用GeneMANIA网站分析了HGH1的蛋白相互作用信息。基于单变量Cox回归和Kaplan-Meier方法，我们评估了HGH1在BRCA预后中的作用。我们使用 GO、KEGG 和 GSEA 分析了与 HGH1 相关的差异表达基因。我们还研究了 HGH1 表达、免疫检查点和免疫浸润之间的关系。我们使用CCK-8、EdU和集落形成试验来测量细胞增殖，并使用Western印迹分析来评估HGH1在BRCA中的作用。IHC结果显示，与正常组织相比，HGH1在BRCA组织中的表达明显上调。高水平的HGH1表达与较差的临床特征和较差的预后有关。在单变量和多变量分析中，HGH1的表达是BRCA预后的独立预测因子。功能方面，Western印迹分析表明，HGH1与细胞周期有关。此外，敲除 HGH1 能显著降低 BRCA 细胞的增殖能力。重要的是，HGH1的表达水平与Th2细胞浸润呈正相关，而与Tcm细胞浸润呈负相关。HGH1等生物标志物可以可靠地预测BRCA患者的预后。

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The role of HGH1 in breast cancer prognosis: a study on immune response and cell cycle

Breast cancer (BRCA) remains to be among the main causes of cancer-associated mortality in women globally. HGH1 homolog (HGH1) has been reported to be associated with tumor immunity. However, the function of HGH1 in BRCA remains unclear. Therefore, the present study examined the potential role of HGH1 in BRCA. The Cancer Genome Atlas (TCGA) databases and Gene Expression Omnibus (GEO) were used to obtain RNA-seq data for BRCA. A protein localization of HGH1 was determined by using the Human Protein Atlas (HPA), and immunohistochemistry (IHC) staining revealed an upregulation in the expression of HGH1 in clinical BRCA tissues. Xenograft mice were used to test tumor growth and HGH1 expression in breast cancer cells. The protein interaction information of HGH1 was analyzed using the GeneMANIA website. Based on univariate Cox regression and Kaplan-Meier methods, we evaluated the role of HGH1 in BRCA prognosis. HGH1-related differentially expressed genes were analyzed using GO, KEGG, and GSEA. We also examined the relationship between HGH1 expression, immune checkpoints, and immune infiltration. CCK-8, EdU, and colony formation assays were used to measure cell proliferation, and western blot analysis was used to evaluate HGH1’s role in BRCA. IHC results showed that the expression of HGH1 was significantly upregulated in BRCA tissues compared to normal tissues. High levels of HGH1 expression was associated with worse clinical features and a worse prognosis. HGH1 expression was an independent predictor of BRCA outcomes in both univariate and multivariate analyses. Functionally, western blot analysis showed that HGH1 is implicated in cell cycle. As well, knocking down HGH1 significantly reduced BRCA cells’ proliferative abilities. Crucially, HGH1 expression levels were positively correlated with Th2 cell infiltration and negatively correlated with Tcm cell infiltration. Biomarkers such as HGH1 can reliably predict prognosis in BRCA patients.

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来源期刊

BMC Cancer 医学-肿瘤学

CiteScore

6.00

自引率

2.60%

发文量

1204

审稿时长

6.8 months

期刊介绍： BMC Cancer is an open access, peer-reviewed journal that considers articles on all aspects of cancer research, including the pathophysiology, prevention, diagnosis and treatment of cancers. The journal welcomes submissions concerning molecular and cellular biology, genetics, epidemiology, and clinical trials.