HAUS5 Is A Potential Prognostic Biomarker With Functional Significance in Breast Cancer

Zhijian Huang; Jiasheng Yang; Wenjing Qiu; Jing Huang; Zhirong Chen; Yuanyuan Han; Changsheng Ye

doi:10.3389/fonc.2022.829777

HAUS5 Is A Potential Prognostic Biomarker With Functional Significance in Breast Cancer

Front Oncol. 2022 Feb 25:12:829777. doi: 10.3389/fonc.2022.829777. eCollection 2022.

Authors

Zhijian Huang^{1

2}, Jiasheng Yang³, Wenjing Qiu³, Jing Huang⁴, Zhirong Chen⁵, Yuanyuan Han⁶, Changsheng Ye¹

Affiliations

¹ Breast Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
² Department of Breast Surgical Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China.
³ School of Electrical and Information Engineering, Anhui University of Technology, Maanshan, China.
⁴ Department of Pharmacy, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China.
⁵ Biomedical Research Center of South China, Fujian Normal University, Fuzhou, China.
⁶ Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.

Abstract

Background: 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.

Methods: 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.

Result: 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.

Conclusion: 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.

Keywords: HAUS5; bioinformatics; biomarker; breast cancer; immune infiltration; prognosis.