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. 2021 Dec 1:14:9181-9191.
doi: 10.2147/IJGM.S343948. eCollection 2021.

Bioinformatic Analysis of Prognostic Value, Genetic Interaction, and Immune Infiltration of Chromobox Family Proteins in Breast Cancer

Guochao Mao  1 , Yi Zheng  1 , Shuai Lin  1 , Li Ma  1 , Zhangjian Zhou  1 , Shuqun Zhang  1
Affiliations

Bioinformatic Analysis of Prognostic Value, Genetic Interaction, and Immune Infiltration of Chromobox Family Proteins in Breast Cancer

Guochao Mao et al. Int J Gen Med. .

Abstract

Introduction: Breast cancer (BC) has become the malignant tumor with the highest incidence worldwide. As a critical components of epigenetic regulation complexes, chromobox (CBX) family members inhibit the transcription of target genes through chromatin modification, leading to the progression of various human diseases and cancers. So far, little is known about the role of different CBX members in BC, especially their association with immune cells.

Methods: We conducted the analysis of differential expression of CBXs using Oncomine and GEPIA, prognostic value of CBXs using GEPIA and Kaplan-Meier, genetic interaction of CBXs using cBioPortal and GeneMANIA, and immune cell infiltration of CBXs in BC patients using TIMER.

Results: The CBX2/3/4/8 expression levels were increased significantly, while the CBX6/7 expression levels were decreased. We found that CBX3 was significantly correlated with clinicopathological staging and short DFS in BC patients. High CBX3/5 expression was correlated with short OS in BC patients, while high expression of CBX4 was correlated with long OS in BC patients. In addition, the functions of CBXs family members mainly focus on methylated histone residue binding and chromatin organization. The CBXs expressions were closely related to the infiltration level of a variety of immune cells, including CD4/8+ T cells, B cells, neutrophils, macrophages and dendritic cells in BC cancers. The correlation between CBXs and immune cell infiltration was more common in Luminal BC than in Basal and Her-2 type.

Conclusion: This study may provide a new understanding for selection of molecular typing, therapeutic and prognostic biomarkers of CBX family in BC.

Keywords: breast cancer; chromobox family members; comprehensive analysis; genetic interaction; immune infiltration; prognosis.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
The mRNA expression of CBX family proteins in different cancers in Oncomine. Red indicates increased expression and blue indicates decreased expression.
Figure 2
Figure 2
The mRNA expression of CBX family proteins in BC in GEPIA. Red indicates increased expression and green indicates decreased expression.
Figure 3
Figure 3
Correlation between CBXs expression and clinicopathological staging of BC in GEPIA. (A–H). Correlation between CBX1 (A), CBX2 (B), CBX3 (C), CBX4 (D), CBX5 (E), CBX6 (F), CBX7 (G), CBX8 (H) and clinicopathological staging of BC determined by GEPIA. CBX2 was highly correlated, followed by CBX1 also has a high correlation, while the remaining six groups were not significantly different.
Figure 4
Figure 4
Prognostic evaluation of CBXs mRNA expression in BC patients (GEPIA). (B). High level of CBX2 mRNA expression in BC patients was significantly correlated with OS. (D). High level of CBX4 mRNA expression in BC patients was significantly correlated with DFS. CBX1 (A), CBX3 (C), CBX5 (E), CBX6 (F), CBX7 (G) and CBX8 (H) mRNA expression in BC patients were not associated with OS or DFS.
Figure 5
Figure 5
Prognostic evaluation of CBXs mRNA expression in BC patients (Kaplan-Meier plotter). High expression of CBX3/5 mRNA was significantly correlated with short OS, and high expression of CBX4/6 and CBX7 were significantly associated with long OS in BC patients.
Figure 6
Figure 6
Gene alteration and interaction of CBXs in BC patients. (A, B) Gene alteration and expression of CBXs in BC patients (cBioPortal). (C, D) Analysis of protein-protein interaction of CBXs (STRING and GeneMANIA).
Figure 7
Figure 7
Correlation between immune cell infiltration and CBXs in BC patients and Luminal BC determined by TIMER.
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