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Original Study|Articles in Press

Comprehensive Analysis of the Expression and Prognosis of chromobox Family Members in Breast Cancer

  • Lu Wang
    Affiliations
    Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province 710061, China
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  • Lin Zhao
    Affiliations
    Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province 710061, China
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  • Yujiao Zhang
    Affiliations
    Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province 710061, China
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  • Shan Shao
    Affiliations
    Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province 710061, China
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  • Qian Ning
    Affiliations
    Department of Respiratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province 710061, China
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  • Xinhan Zhao
    Correspondence
    Address for correspondence: Xinhan Zhao, MD, Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xian Jiao tong University, Xi'an, Shaanxi Province 710061, China
    Affiliations
    Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province 710061, China
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  • Minna Luo
    Correspondence
    Address for correspondence: Minna Luo, MD, Department of Hematology, The First Affiliated Hospital of Xi'an Jiaotong University, Xian Jiao tong University, Xi'an, Shaanxi Province 710061, China
    Affiliations
    Department of Hematology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province 710061, China
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Published:February 15, 2023DOI:https://doi.org/10.1016/j.clbc.2023.02.007

      Highlights

      • The expression of chromobox (CBX) family members was varied in breast cancer and several members of CBX family were associated with molecular subclasses, tumor stages, lymph node status and TP53 mutational status.
      • Higher expression of CBX2/3 was associated with worse overall survival, postprogression survival, relapse-free survival, and distant metastasis-free survival, which indicated a poor prognosis while higher levels of CBX 6/7 may represent a better prognosis.
      • CBX family may serve as an important regulator in breast cancer and its functional role is worthy of further study.

      Abstract

      Background: Chromobox proteins are canonical components of the Polycomb group family and play pivotal roles in several cancers. However, little is known about the function, prognostic value and drug sensitivity of CBX family members in breast cancer.Methods: In this study we investigated the expression, prognosis value and drug sensitivity of CBX family in breast cancer using the ONCOMINE, GEPIA, Human Protein Atlas and Kaplan-Meier Plotter databases, etc. and preliminary verified the expression of CBX family in breast cancer cell lines by RT-qPCR.Results: We found that the expression levels of CBX1/2/3/4/8 members were elevated in breast cancer tissues compared to adjacent normal breast tissues, while the expression levels of CBX6/7 genes were reduced in breast cancer tissue. In vitro qRT-PCR validated the expression differences of CBX1/2/3/4/8 in breast cancer cell lines. Further analysis showed expression of CBX family members was remarkably correlated with cancer subgroups. As nodal metastasis status increased, the mRNA expression of CBX1/2/3/4/8 members tended to be higher, while CBX6/7 tended to be lower. The expression of CBX1/2/3 was higher in patients with TP53 mutation and CBX6/7 expression tended to be lower in patients with TP53 mutation groups. High transcription levels of CBX2/3 were significantly associated with shorter overall survival in breast cancer patients, while lower expression of CBX4/5/6/7 members was associated with unfavorable overall survival. Moreover, a high mutation rate of CBX gene members (43%) was observed in breast cancer patients, and genetic alterations in CBX genes was associated with poor prognosis.Conclusion: Taken together, our results indicated that CBX2/3/6/7/8 could be considered prognostic and therapeutic biomarkers of breast cancer and are worthy of further study.

      Keywords

      Abbreviations:

      CBX (Chromobox), ER (estrogen receptor), PR (progesterone receptor), Her2 (human epidermal receptor 2), TNBC (triple-negative breast cancer), FC (fold-change), TCGA (The Cancer Genome Atlas), GO (Gene Ontology), KEGG (Kyoto Encyclopedia of Genes and Genomes), PPI (protein-protein interaction), OS (overall survival relapse-free survival), PPS (postprogression survival), RFS (relapse-free survival), DMFS (distant metastasis-free survival)
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