Prognostic and Therapeutic Significance of Adhesion-regulating Molecule 1 in Estrogen Receptor-positive Breast Cancer

Wu, Wanbo; Zhong, Jing; Chen, Jing; Niu, Pingping; Ding, Yunfeng; Han, Shuwen; Xu, Jiewei; Dai, Licheng

doi:10.1016/j.clbc.2019.07.009

Cited by 4 publications

(3 citation statements)

References 26 publications

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“…Subgroup of Q1 was 0 to 25% percentile; Q2 was 25% to the median; Q3 was the median to 75% percentile; and Q4 was 75% percentile to maximum. For further analysis, less than the value of the median was regarded as CIT-low, and greater or equal to the median was CIT-high [12].…”

Section: Associations Of Cit Expression With Clinical Characteristicsmentioning

confidence: 99%

Overexpression of Citron Rho-Interacting Serine/Threonine Kinase Associated with Poor Outcome in Bladder Cancer

Shou¹,

Yu²,

Zhang³

et al. 2020

J. Cancer

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Objective: Citron Rho-Interacting Serine/Threonine Kinase (CIT) was originally identified as a binding partner of active forms of the small GTPases Rho and Rac. This kinase participated in the regulation of cytokinesis and loss of CIT was associated with chromosomal instability. Here, we assume that CIT might be a potential prognostic biomarker for bladder cancer. Materials and Methods: The expression and prognostic significance of CIT mRNA were validated on 5 published microarray data sets, including 948 bladder cancer cases. To further confirm the results, we collected 54 non-carcinomatous human bladder tissue samples and 315 bladder cancer tissues from Zhejiang Provincial People's Hospital to detect the protein level of CIT based on the immunohistochemistry analysis. The Kaplan-Meier method and Cox proportional hazards regression model were used in survival analysis. Results: Analysis results showed that high CIT expression was associated with tumor size (p=0.0001), tumor grade (p<0.0001), smoking status (p=0.0143), TNM stage (p=0.0024), pathological tumor stage (p<0.0001) and aggressive phenotypes of bladder cancer. Independent and pooled survival analyses both indicated that overexpression of CIT was significantly associated with poor survival of bladder cancers. Conclusions: In conclusion, these findings indicated that overexpression of CIT was significantly associated with poor survival outcome in bladder cancers. CIT might serve as a promising prognostic biomarker and therapeutic target for bladder cancers.

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Section: Associations Of Cit Expression With Clinical Characteristicsmentioning

confidence: 99%

Overexpression of Citron Rho-Interacting Serine/Threonine Kinase Associated with Poor Outcome in Bladder Cancer

Shou¹,

Yu²,

Zhang³

et al. 2020

J. Cancer

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“…ADRM1 is involved in proteasome composition and acts as a ubiquitin receptor to recruit deubiquitinating enzymes [36,37]. Aberrant expression of ADRM1 is associated with a variety of cancers [38][39][40][41]. SLC12A7, also known as KCC4, is involved in cell volume homeostasis, inorganic ion homeostasis and transmembrane transport [42][43][44].…”

Section: Discussionmentioning

confidence: 99%

HMG20A was identified as a key enhancer driver associated with DNA damage repair in oral squamous cell carcinomas

Zhang

Wenjing

et al. 2022

BMC Oral Health

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Background Oral squamous cell carcinoma (OSCC) is the main type of oral cancer. Disturbing DNA repair is an invaluable way to improve the effectiveness of tumor treatment. Here, we aimed to explore the key enhancer drivers associated with DNA damage repair in OSCC cells. Methods Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA) and Kaplan-Meier analysis were applied to explore the relationship among DNA repair-related genes expression and clinical phenotypes based on The Cancer Genome Atlas (TCGA) database. HOMER software and Integrative Genomics Viewer were applied to identify and visualize enhancers using GSE120634. Toolkit for Cistrome Data Browser was applied to predict transcription factors. Human Protein Atlas Database was used to analyze the protein levels of transcription factors in OSCC and control tissues. Seventy-two OSCC patients were included in this study. qRT-PCR was used to detect transcription factor expression in OSCC and adjacent control tissues collected in this study. qRT-PCR and ChIP-qPCR were used to verify the binding of transcription factors to enhancers, and regulation of target genes transcription. Transcription factor knockdown and control cells were treated with cisplatin. CCK8 was used to detect cell viability and proliferation. Western blotting was implemented to detect the levels of DNA repair-related proteins. Transwell assay was used to detect cell invasion. Results DNA repair was positively associated with the OSCC metastatic phenotype. Patients in the cluster with high expression of DNA repair-related genes had a worse prognosis and a higher proportion of advanced stage, low-differentiation, alcohol consumption and smoking compared to the cluster with low DNA repair-related gene expression. Seventeen metastasis-specific enhancer-controlled upregulated DNA repair-related genes, with the top two upregulated genes being ADRM1 26 S proteasome ubiquitin receptor (ADRM1) and solute carrier family 12 member 7 (SLC12A7) were screened. High mobility group 20 A (HMG20A) was the key prognostic enhancer driver regulating metastasis-specific DNA repair-related genes, with higher expression in OSCC tissues than normal control tissues, and higher expression in metastatic OSCC tissues than non-metastatic OSCC tissues. HMG20A bound to the metastasis-specific enhancers of ADRM1 and SLC12A7, thereby promoting ADRM1 and SLC12A7 expression. Knockdown of HMG20A enhanced cisplatin sensitivity of cells, and inhibited OSCC cells from repairing DNA damage caused by cisplatin, as well as proliferation and invasion of OSCC cells. Conclusion HMG20A was identified as the key prognostic enhancer driver regulating DNA repair in OSCC cells, providing a new therapeutic target for OSCC.

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“…Within the context of human cancers, deubiquitinating proteins are increasingly recognized as pivotal oncogenes or tumor suppressor genes across various malignancies 17 . Notably, recent studies have highlighted a correlation between elevated ADRM1 expression and unfavorable overall survival (OS) in distinct malignancies, such as hepatocellular carcinoma 18 , gastric cancer 19 , and breast cancer 20 . Specifically, inhibiting ADRM1 would suppress cancer cells growth in vitro 18 , 21 .…”

Section: Introductionmentioning

confidence: 99%

Adhesion-regulating molecule 1 (ADRM1) can be a potential biomarker and target for bladder cancer

Yu,

Wang,

Liu

et al. 2023

Sci Rep

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Adhesion-regulating molecule 1 (ADRM1) has been implicated in tumor development, yet its specific role in bladder cancer (BC) remains undefined. This study aimed to elucidate the function of ADRM1 in BC through a combination of bioinformatics analysis and immunohistochemical analysis (IHC). Utilizing R version 3.6.3 and relevant packages, we analyzed online database data. Validation was conducted through IHC data, approved by the Institutional Ethics Committee (Approval No. K20220830). In both paired and unpaired comparisons, ADRM1 expression was significantly elevated in BC tissues compared to adjacent tissues, as evidenced by the results of TCGA dataset and IHC data. Patients with high ADRM1 expression had statistically worse overall survival than those with low ADRM1 expression in TCGA dataset, GSE32548 dataset, GSE32894 dataset, and IHC data. Functional analysis unveiled enrichment in immune-related pathways, and a robust positive correlation emerged between ADRM1 expression and pivotal immune checkpoints, including CD274, PDCD1, and PDCD1LG2. In tumor microenvironment, samples with the high ADRM1 expression contained statistical higher proportion of CD8 + T cells and Macrophage infiltration. Meanwhile, these high ADRM1-expressing samples displayed elevated tumor mutation burden scores and stemness indices, implying potential benefits from immunotherapy. Patients with low ADRM1 expression were sensitive to cisplatin, docetaxel, vinblastine, mitomycin C, and methotrexate. According to the findings from bioinformatics and IHC analyses, ADRM1 demonstrates prognostic significance for BC patients and holds predictive potential for both immunotherapy and chemotherapy responses. This underscores its role as a biomarker and therapeutic target in BC.

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Prognostic and Therapeutic Significance of Adhesion-regulating Molecule 1 in Estrogen Receptor-positive Breast Cancer

Cited by 4 publications

References 26 publications

Overexpression of Citron Rho-Interacting Serine/Threonine Kinase Associated with Poor Outcome in Bladder Cancer

Overexpression of Citron Rho-Interacting Serine/Threonine Kinase Associated with Poor Outcome in Bladder Cancer

HMG20A was identified as a key enhancer driver associated with DNA damage repair in oral squamous cell carcinomas

Adhesion-regulating molecule 1 (ADRM1) can be a potential biomarker and target for bladder cancer

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