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Updated: Nov 17, 2025

Performing Data Mining And Integrative Analysis Of Biomarker in Breast Cancer Using Multiple Publicly Accessible Databases
Published on: May 17, 2019
CLIP4 Shows Putative Tumor Suppressor Characteristics in Breast Cancer: An Integrated Analysis
1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Academician (Expert) Workstation of Sichuan Province, Luzhou, China.
Abstract:
Background: CAP-Gly domain containing linker protein family member 4 (CLIP4) plays an important role in cancers. However, its expression, prognostic value, and biological effect in breast cancer remain unclear. Methods: Data on patients diagnosed with breast cancer were retrieved from the TCGA-BRCA and other public omics databases. The expression profile of CLIP4 was analyzed using Oncomine, bc-GenExMiner, and TCGA. The prognostic value of CLIP4 was determined by Kaplan-Meier Plotter and Human Protein Atlas. Identification of genes co-expressed with CLIP4 and potential mechanism analyses were performed using UALCAN, STRING, Metascape, and GSEA. The epigenetic characteristics of CLIP4 were determined by DiseaseMeth and MEXPRESS. Results: CLIP4 was downregulated and its expression was negatively correlated with estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor type 2 (HER2) status, Nottingham prognostic index (NPI), and Scarff-Bloom-Richardson (SBR) grade in breast cancer, whereas it was positively linked to basal-like and triple negative breast cancer status. Ectopic expression of CLIP4 was related with poor prognosis. In the analysis of genes co-expressed with CLIP4, GSEA showed that the Hedgehog (Hh), JAK-STAT, ERBB, Wnt signaling pathway, cell adhesion molecules, and pathways in cancer were dissimilarly enriched in the CLIP4 expression high phenotype. Analysis of the genetics and epigenetics of CLIP4 indicated that its expression was negatively correlated with DNA methylation. Conclusion: Methylated CLIP4 may be a novel prognostic and therapeutic biomarker for breast cancer.
Insights
Downregulated CAP-Gly domain containing linker protein family member 4 (CLIP4) in breast cancer correlates with poor prognosis and is linked to methylation. Methylated CLIP4 may serve as a novel biomarker.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- CAP-Gly domain containing linker protein family member 4 (CLIP4) has known roles in various cancers.
- Its specific role, expression, and prognostic significance in breast cancer are not well understood.
Purpose of the Study:
- To investigate the expression, prognostic value, and biological mechanisms of CLIP4 in breast cancer.
- To explore CLIP4's potential as a biomarker for breast cancer prognosis and therapy.
Main Methods:
- Utilized TCGA-BRCA and other public omics databases for expression and prognostic analyses.
- Employed bioinformatics tools (Oncomine, Kaplan-Meier Plotter, GSEA, STRING, Metascape) for gene co-expression, pathway enrichment, and epigenetic analysis.
- Investigated genetic and epigenetic factors, including DNA methylation, influencing CLIP4 expression.
Main Results:
- CLIP4 expression was downregulated in breast cancer and negatively correlated with ER, PR, HER2 status, NPI, and SBR grade.
- Higher CLIP4 expression was associated with basal-like and triple-negative breast cancer subtypes and linked to poor prognosis.
- Enrichment analysis revealed associations with Hedgehog, JAK-STAT, ERBB, Wnt signaling pathways, and cell adhesion molecules.
- CLIP4 expression inversely correlated with DNA methylation levels.
Conclusions:
- Downregulated and methylated CLIP4 is associated with aggressive breast cancer subtypes and poor prognosis.
- CLIP4, particularly its methylated form, shows potential as a novel prognostic and therapeutic biomarker for breast cancer.
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