Huang Zhijian, Yang Jiasheng, Qiu Wenjing, Huang Jing, Chen Zhirong, Han Yuanyuan, Ye Changsheng
Breast Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Breast Surgical Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China.
Front Oncol. 2022 Feb 25;12:829777. doi: 10.3389/fonc.2022.829777. eCollection 2022.
Breast cancer (BRCA) has become the most frequently appearing, lethal, and aggressive cancer with increasing morbidity and mortality. Previously, it was discovered that the HAUS5 protein is involved in centrosome integrity, spindle assembly, and the completion of the cytoplasmic division process during mitosis. By encouraging chromosome misdivision and aneuploidy, HAUS5 has the potential to cause cancer. The significance of HAUS5 in BRCA and the relationship between its expression and clinical outcomes or immune infiltration remains unclear.
Pan-cancer was analyzed by TIMER2 web and the expression differential of HAUS5 was discovered. The prognostic value of HAUS5 for BRCA was evaluated with KM plotter and confirmed with Gene Expression Omnibus (GEO) dataset. Following that, we looked at the relationship between the high and low expression groups of HAUS5 and breast cancer clinical indications. Signaling pathways linked to HAUS5 expression were discovered using Gene Set Enrichment Analysis (GSEA). The relative immune cell infiltrations of each sample were assessed using the CIBERSORT algorithm and ESTIMATE method. We evaluated the Tumor Mutation Burden (TMB) value between the two sets of samples with high and low HAUS5 expression, as well as the differences in gene mutations between the two groups. The proliferation changes of BRCA cells after knockdown of HAUS5 were evaluated by fluorescence cell counting and colony formation assay.
HAUS5 is strongly expressed in most malignancies, and distinct associations exist between HAUS5 and prognosis in BRCA patients. Upregulated HAUS5 was associated with poor clinicopathological characteristics such as tumor T stage, ER, PR, and HER2 status. mitotic prometaphase, primary immunodeficiency, DNA replication, cell cycle related signaling pathways were all enriched in the presence of elevated HAUS5 expression, according to GSEA analysis. The BRCA microenvironment's core gene, HAUS5, was shown to be related with invading immune cell subtypes and tumor cell stemness. TMB in the HAUS5-low expression group was significantly higher than that in the high expression group. The mutation frequency of 15 genes was substantially different in the high expression group compared to the low expression group. BRCA cells' capacity to proliferate was decreased when HAUS5 was knocked down.
These findings show that HAUS5 is a positive regulator of BRCA progression that contributes to BRCA cells proliferation. As a result, HAUS5 might be a novel prognostic indicator and therapeutic target for BRCA patients.
乳腺癌（BRCA）已成为发病率和死亡率不断上升的最常见、致命且侵袭性强的癌症。此前发现，HAUS5蛋白参与中心体完整性、纺锤体组装以及有丝分裂期间细胞质分裂过程的完成。通过促进染色体错分和非整倍体形成，HAUS5有可能引发癌症。HAUS5在乳腺癌中的意义及其表达与临床结局或免疫浸润之间的关系仍不清楚。
通过TIMER2网站分析泛癌情况并发现HAUS5的表达差异。使用KM plotter评估HAUS5对乳腺癌的预后价值，并通过基因表达综合数据库（GEO）数据集进行确认。随后，我们研究了HAUS5高表达组和低表达组与乳腺癌临床指标之间的关系。使用基因集富集分析（GSEA）发现与HAUS5表达相关的信号通路。使用CIBERSORT算法和ESTIMATE方法评估每个样本的相对免疫细胞浸润情况。我们评估了HAUS5高表达组和低表达组两组样本之间的肿瘤突变负荷（TMB）值以及两组之间基因突变的差异。通过荧光细胞计数和集落形成试验评估敲低HAUS5后乳腺癌细胞的增殖变化。
HAUS5在大多数恶性肿瘤中高表达，且HAUS5与乳腺癌患者的预后存在明显关联。HAUS5上调与不良临床病理特征相关，如肿瘤T分期、雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体2（HER2）状态。根据GSEA分析，有丝分裂前中期、原发性免疫缺陷、DNA复制、细胞周期相关信号通路在HAUS5表达升高时均富集。研究表明，乳腺癌微环境的核心基因HAUS5与侵袭性免疫细胞亚型和肿瘤细胞干性相关。HAUS5低表达组的TMB显著高于高表达组。高表达组与低表达组相比，15个基因的突变频率存在显著差异。敲低HAUS5后，乳腺癌细胞的增殖能力下降。
这些发现表明，HAUS5是乳腺癌进展的正调节因子，有助于乳腺癌细胞增殖。因此，HAUS5可能是乳腺癌患者的一种新型预后指标和治疗靶点。
