Bioinformatic analysis of the expression and prognostic value of chromobox family proteins in human breast cancer

Li, Xiaomin; Gou, Junhe; Li, Hongjiang; Yang, Xiaoqin

doi:10.1038/s41598-020-74792-5

Cited by 26 publications

(27 citation statements)

References 40 publications

(53 reference statements)

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“…Downregulated expression levels in cancer tissues have consistently been reported for SENP2 [52][53][54][55][56][57] and PIAS2 [58][59][60]. The prognostic value of a single SUMO machinery component can also vary between cancer (sub)types, and, e.g., the value for PC2 [61,62] and PIAS4 [63,64] as prognostic biomarkers in breast cancer and for PIAS3 [65,66] in mesothelioma remains ambiguous (Table 1). Bioinformatic analyses of the SUMO machinery protein and mRNA levels, and their association with prognosis, utilizing datasets from various databases are generally well in line with the other published analyses of often smaller sample sizes [67][68][69] (and Supplementary Table S1).…”

Section: Altered Expression and Prognostic Significance Of Sumo Pathway In Cancermentioning

confidence: 99%

Therapeutic Potential of Targeting the SUMO Pathway in Cancer

Kukkula

Ojala

Mendez

et al. 2021

Cancers

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SUMOylation is a dynamic and reversible post-translational modification, characterized more than 20 years ago, that regulates protein function at multiple levels. Key oncoproteins and tumor suppressors are SUMO substrates. In addition to alterations in SUMO pathway activity due to conditions typically present in cancer, such as hypoxia, the SUMO machinery components are deregulated at the genomic level in cancer. The delicate balance between SUMOylation and deSUMOylation is regulated by SENP enzymes possessing SUMO-deconjugation activity. Dysregulation of SUMO machinery components can disrupt the balance of SUMOylation, contributing to the tumorigenesis and drug resistance of various cancers in a context-dependent manner. Many molecular mechanisms relevant to the pathogenesis of specific cancers involve SUMO, highlighting the potential relevance of SUMO machinery components as therapeutic targets. Recent advances in the development of inhibitors targeting SUMOylation and deSUMOylation permit evaluation of the therapeutic potential of targeting the SUMO pathway in cancer. Finally, the first drug inhibiting SUMO pathway, TAK-981, is currently also being evaluated in clinical trials in cancer patients. Intriguingly, the inhibition of SUMOylation may also have the potential to activate the anti-tumor immune response. Here, we comprehensively and systematically review the recent developments in understanding the role of SUMOylation in cancer and specifically focus on elaborating the scientific rationale of targeting the SUMO pathway in different cancers.

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Section: Altered Expression and Prognostic Significance Of Sumo Pathway In Cancermentioning

confidence: 99%

Therapeutic Potential of Targeting the SUMO Pathway in Cancer

Kukkula

Ojala

Mendez

et al. 2021

Cancers

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“…The CBX family of genes is thought to represent vital elements in a variety of tumors (14)(15)(16). However, the association between CBXs and sarcoma has not been extensively reported.…”

Section: Discussionmentioning

confidence: 99%

“…found that HP1- α/β/γ (CBX1/3/5) and CBX2/4/6/7 exerted an effect on breast cancer, thus indicating that CBX2 is expressed at high levels in basal-like and HER-2 subtypes ( 14 ). In addition, CBX4/7 is highly expressed in Luminal A and Luminal B subtypes of breast cancer ( 14 , 15 ). The increased mRNA expression of HP1- β/γ (CBX1/3) and CBX2 has been linked to a poorer Relapse free survival (RFS) via survival analysis; better outcomes were found to be associated with higher expression levels of CBX4/5/6/7 ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

Prognosis and Immune Infiltration of Chromobox Family Genes in Sarcoma

et al. 2021

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BackgroundChromobox family genes (CBXs) are known to play roles in numerous modifications of the chromatin in order to inhibit the transcription of target genes. CBXs have been shown to be expressed at high levels in many types of cancer and can also serve as a target gene for therapeutic purposes. However, little is known about the expression and prognostic value of CBXs in human sarcomas.MethodsThe transcription level of CBXs was analyzed using the Oncomine dataset, and the differential expression of CBXs in sarcoma was reported by the Gene Expression Profiling Interactive Analysis (GEPIA) dataset. We also used the CCLE dataset to evaluate the expression of CBXs in a sarcoma cell line. The prognostic value of CBXs was analyzed using GEPIA and Kaplan–Meier analysis. In addition, the corrections between CBXs and their co-expressed genes were reported using Oncomine and GEPIA datasets. DAVID was used to perform GO function enrichment analysis for the CBXs and their co-expression genes. Finally, TIMER was used to analyze the immune cell infiltration of CBXs in patients with sarcoma.ResultsHP1-α/β/γ (CBX1/3/5) and CBX4/6/8 were found to be overexpressed in human sarcoma, and CBXs were upregulated in almost all the sarcoma cell line. The expression levels of HP1-α/β/γ (CBX1/3/5) and CBX7 were associated with overall survival (OS) in patients with sarcoma, while high expression levels of CBX7 were related to disease-free survival (DFS). In addition, the expression levels of CBX2/6/7 were related to recurrence-free survival (RFS). We also found that the CBX family was positively correlated with the infiltration of immune cells, including CD8+ T cells, CD4+ T cells, B cells, macrophages, neutrophils, and dendritic cells, in sarcoma.ConclusionsThe results from the present study indicated that CBXs were significantly associated with prognosis and immunological status in sarcoma. These data suggest that CBXs could serve as potential biomarkers for prognosis and immune infiltration in human sarcoma.

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“…Chromobox (CBX) family proteins are canonical components of polycomb group (PcG) complexes, which contain a single N-terminal chromodomain [7,8]. The CBX family of proteins is reported to be involved in various biological processes, such as cell cycle regulation, cell cycle regulation, gene expression, and tumor initiation.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis of Prognostic and Immune Infiltrates for CBX Family in Human Pancreatic Adenocarcinoma

Li¹,

Fu²,

wu³

et al. 2021

Preprint

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Background: Pancreatic adenocarcinoma (PAAD) is one of the common Malignant tumours of the digestive tract worldwide. Chromobox (CBX) family proteins are important components of epigenetic regulation complexes and play key roles in various biological processes. However, the expression level, biological function and immune infiltration of different E2Fs in PAAD and prognostic roles of various CBX family members in Pancreatic adenocarcinoma (PAAD) remain unclear.Methods: In this study, we used multiple bioinformatics tools including Oncomine, GEPIA, Kaplan-Meier plotter, cBioPortal, GeneMANIA, TIMER and R Tools to analyze expression levels, prognostic value, genetic alteration, immune cell infiltration and risk factors of CBXs in Pancreatic adenocarcinoma patients. Furthermore, we confirmed the expression of CBX3 on clinic pathological specimens by immunohistochemistry.Results: The expression levels of CBX1/3/5/8 were significantly elevated in PAAD tissues, and the high expression of CBX1/5/6/7 was associated with the tumor stage of patients. Higher mRNA expression of CBX2/6/7 and CBX8 were significantly associated with favorable OS of pancreatic cancer patients, while higher expression of CBX3 was significantly associated with short OS. We verified the high expression of CBX3 in pancreatic cancer tissues on clinicopathological specimens. Multivariate logistic analysis demonstrated that high mRNA expressions of CBX3 and low expression of CBX8 were independent risk factors for shorter survival of pancreatic carcinoma patients. The functions of CBXs and its neighboring proteins are mainly related to negative regulation of cell cycle process, PcG protein complex, histone binding and regulating pluripotency of stem cells signaling pathways. We also found that the expression of CBXs was significantly correlated with immune infiltrates.Conclusions: Our study may provide new insights into the selection of immunotherapeutic targets and prognostic biomarkers and revealed that CBX3/8 may represent a clinically useful biomarker for predicting overall survival in patients with PAAD.

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Bioinformatic analysis of the expression and prognostic value of chromobox family proteins in human breast cancer

Cited by 26 publications

References 40 publications

Therapeutic Potential of Targeting the SUMO Pathway in Cancer

Therapeutic Potential of Targeting the SUMO Pathway in Cancer

Prognosis and Immune Infiltration of Chromobox Family Genes in Sarcoma

Comprehensive Analysis of Prognostic and Immune Infiltrates for CBX Family in Human Pancreatic Adenocarcinoma

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