Prognostic and Genomic Analysis of Proteasome 20S Subunit Alpha (PSMA) Family Members in Breast Cancer.

Chung-Chieh Chiao,Nam Nhut Phan,Yung-Fu Wu,Gangga Anuraga,Kuen-Haur Lee,Nu Thuy An Ton,Chih-Yang Wang,Vivin Andriani,Purity Sabila Ajiningrum,Do Thi Minh Xuan,Muhammad Athoillah,Yen-Hsi Liu,Hoang Dang Khoa Ta,Elvira Mustikawati Putri Hermanto,Jian-Ying Chuang,Tzu-Jen Kao,Fenny Fitriani

doi:10.3390/diagnostics11122220

Abstract

The complexity of breast cancer includes many interacting biological processes, and proteasome alpha (PSMA) subunits are reported to be involved in many cancerous diseases, although the transcriptomic expression of this gene family in breast cancer still needs to be more thoroughly investigated. Consequently, we used a holistic bioinformatics approach to study the PSMA genes involved in breast cancer by integrating several well-established high-throughput databases and tools, such as cBioPortal, Oncomine, and the Kaplan–Meier plotter. Additionally, correlations of breast cancer patient survival and PSMA messenger RNA expressions were also studied. The results demonstrated that breast cancer tissues had higher expression levels of PSMA genes compared to normal breast tissues. Furthermore, PSMA2, PSMA3, PSMA4, PSMA6, and PSMA7 showed high expression levels, which were correlated with poor survival of breast cancer patients. In contrast, PSMA5 and PSMA8 had high expression levels, which were associated with good prognoses. We also found that PSMA family genes were positively correlated with the cell cycle, ubiquinone metabolism, oxidative stress, and immune response signaling, including antigen presentation by major histocompatibility class, interferon-gamma, and the cluster of differentiation signaling. Collectively, these findings suggest that PSMA genes have the potential to serve as novel biomarkers and therapeutic targets for breast cancer. Nevertheless, the bioinformatic results from the present study would be strengthened with experimental validation in the future by prospective studies on the underlying biological mechanisms of PSMA genes and breast cancer.

Highlights

According to the most up-to-date statistics provided by the World Health Organization (WHO), the progressively increasing estimates of cancer cases and deaths in recent years make it one of the leading causes of premature deaths worldwide [1]
We found that genes coexpressed with PSMA1 were involved in cell cycle-related pathways and networks, such as “Cell cycle_Role of SCF complex in cell cycle regulation”, “Immune response_Antigen presentation by MHC class I, classical pathway”, “Apoptosis and survival_Regulation of apoptosis by mitochondrial proteins”, “Proteolysis_Putative ubiquitin pathway”, and “Ubiquinone metabolism” (Figure 5, Supplementary Table S1)
We recently reported that the high levels of PSMC family members, including PSMC1, PSMC3, PSMC4, PSMC5, and PSMC6, were positively correlated with the poor survival rates of breast cancer (BRCA) patients [45]

Summary

Introduction

According to the most up-to-date statistics provided by the World Health Organization (WHO), the progressively increasing estimates of cancer cases and deaths in recent years make it one of the leading causes of premature deaths worldwide [1]. Lung cancer by far remains the leading killer of both sexes, it was recently displaced by breast cancer (BRCA) in terms of the most frequently diagnosed cases among women. Detection and appropriate treatment are believed to play crucial roles in reducing the immense health and economic burdens imposed and extending the life expectancy for cancer survivors in general and in terms of BRCA due to its invasiveness and aggressiveness. Unremitting efforts have been made to enhance the precision of the prognostic predictions of female BRCA; among these, molecular signatures and targeted therapies have emerged as promising treatment regimens of distinct subtypes [5]

Methods

Results

Discussion

Conclusion