Clinical and Translational Research
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Aug 24, 2022; 13(8): 675-687
Published online Aug 24, 2022. doi: 10.5306/wjco.v13.i8.675
Eight hub genes as potential biomarkers for breast cancer diagnosis and prognosis: A TCGA-based study
Nan Liu, Guo-Duo Zhang, Ping Bai, Li Su, Hao Tian, Miao He
Nan Liu, Guo-Duo Zhang, Ping Bai, Li Su, Miao He, Department of Hematology and Oncology, Chongqing Traditional Chinese Medicine Hospital, Chengdu University of Traditional Chinese Medicine, Chongqing 400011, China
Hao Tian, Department of Breast and Thyroid Surgery, Southwest Hospital, Army Medical University, Chongqing 400038, China
Author contributions: Liu N performed the experiment and wrote the paper; Liu N, Zhang GD, and Bai P contributed to the bioinformatics analysis and figure preparation; Tian H and Su L modified the structure and language of the manuscript; He M and Tian H contributed to the conception and design of the study and the revisions of the manuscript; All authors have read and approved the final manuscript.
Institutional review board statement: Not applicable.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Miao He, MS, Department of Hematology and Oncology, Chongqing Traditional Chinese Medicine Hospital, Chengdu University of Traditional Chinese Medicine, Daomenkou 40, Chongqing 400011, China.
Received: August 2, 2021
Peer-review started: August 2, 2021
First decision: November 6, 2021
Revised: December 23, 2021
Accepted: July 26, 2022
Article in press: July 26, 2022
Published online: August 24, 2022

Breast cancer (BC) is the most common malignant tumor in women.


To investigate BC-associated hub genes to obtain a better understanding of BC tumorigenesis.


In total, 1203 BC samples were downloaded from The Cancer Genome Atlas database, which included 113 normal samples and 1090 tumor samples. The limma package of R software was used to analyze the differentially expressed genes (DEGs) in tumor tissues compared with normal tissues. The cluster Profiler package was used to perform Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of upregulated and downregulated genes. Univariate Cox regression was conducted to explore the DEGs with statistical significance. Protein-protein interaction (PPI) network analysis was employed to investigate the hub genes using the CytoHubba plug-in of Cytoscape software. Survival analyses of the hub genes were carried out using the Kaplan-Meier method. The expression level of these hub genes was validated in the Gene Expression Profiling Interactive Analysis database and Human Protein Atlas database.


A total of 1317 DEGs (fold change > 2; P < 0.01) were confirmed through bioinformatics analysis, which included 744 upregulated and 573 downregulated genes in BC samples. KEGG enrichment analysis indicated that the upregulated genes were mainly enriched in the cytokine-cytokine receptor interaction, cell cycle, and the p53 signaling pathway (P < 0.01); and the downregulated genes were mainly enriched in the cytokine-cytokine receptor interaction, peroxisome proliferator-activated receptor signaling pathway, and AMP-activated protein kinase signaling pathway (P < 0.01).


In view of the results of PPI analysis, which were verified by survival and expression analyses, we conclude that MAD2L1, PLK1, SAA1, CCNB1, SHCBP1, KIF4A, ANLN, and ERCC6L may act as biomarkers for the diagnosis and prognosis in BC patients.

Keywords: Breast cancer, Bioinformatics, Hub gene, The Cancer Genome Atlas, Protein-protein interaction

Core Tip: This study identified 1317 DEGs related to the occurrence and development of breast cancer (BC), 165 DEGs related to prognosis, and 8 hub genes (MAD2L1, PLK1, SAA1, CCNB1, SHCBP1, KIF4A, ANLN, and ERCC6L). Each of these eight hub genes has different expression levels in BC and is significantly related to prognosis. The results of this study indicate that studying these DEGs may help provide a full understanding of the molecular mechanisms underlying BC pathogenesis and progression. Moreover, these hub genes may serve as potential prognostic markers and therapeutic targets, which provide a reference for more in-depth and extensive prospective clinical research.