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Cited by 1Wnt/β-catenin signaling in development and cancerBreast Cancer Treatment StudiesPancreatic and Hepatic Oncology Research

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Comprehensive bioinformatics analysis reveals prognostic significance and immunological roles of WNT gene family in breast cancer

Open access
Fariha, Fatema Tuj Johora, Fuad, Muntasim, Saha, Chandra Shekhar, Hossen, Sajjad, Hossain, Md. Jubayer·2025·Scientific Reports
DOI 10.1038/s41598-025-13315-6PMC PMC12494856

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Abstract

Breast cancer (BRCA) is one of the most commonly diagnosed cancers and the leading cause of cancer-related deaths among women worldwide. Previous studies have shown that the WNT (wingless type) gene family plays a role in the development of various cancers. However, comprehensive analysis of WNTs in BRCA remains largely unexplored. In this study, we examined the expression patterns, clinical relevance, and survival outcomes associated with the WNT family and identified key prognostic WNTs. We further investigated genetic alterations, DNA methylation, and drug sensitivity using cBioPortal, SMART, and GSCA databases. Data from GEO and DepMap were used for validation. Our findings revealed that while WNT2 and WNT7B were significantly upregulated and WNT11 was downregulated, WNT2 paradoxically correlated with favorable prognosis despite its oncogenic overexpression. Amplification was the most common type of alteration among the key WNTs selected for analysis and was correlated with immune infiltration and immunotherapy-related biomarkers. Functional enrichment analysis uncovered a novel connection between WNT signaling and neurodegenerative pathways. Furthermore, co-expression and drug sensitivity analyses revealed that WNTs influence the efficacy of multiple anti-cancer agents, offering potential targets for precision oncology. This study provides novel insights into the multifaceted role of WNT genes in BRCA, identifying them as promising prognostic indicators and immunotherapeutic targets that warrant further clinical exploration.

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Crossref · 10.1038/s41598-025-13315-6

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Figures

Fig. 1 Expression pattern of WNTs in Breast cancer. A mRNA expression pattern of WNTs in breast cancer patients. Heat Map displaying the expression patterns of WNTs using UCSC XENA. Box-and-whisker plots displaying the relative mRNA expression levels of B WNT2, C WNT7B, D WNT11, across TCGA-BRCA and normal samples. Grey-and red-colored box areas signify normal and tumor patient samples. *P < 0.05.)
Fig. 1 Expression pattern of WNTs in Breast cancer. A mRNA expression pattern of WNTs in breast cancer patients. Heat Map displaying the expression patterns of WNTs using UCSC XENA. Box-and-whisker plots displaying the relative mRNA expression levels of B WNT2, C WNT7B, D WNT11, across TCGA-BRCA and normal samples. Grey-and red-colored box areas signify normal and tumor patient samples. *P < 0.05.)CC BY · PubMed Central
Fig. 2 Expression pattern of highly deregulated WNTs in BC based on clinicopathological characteristics by UALCAN database. Expression pattern of WNT2, WNT7B, WNT11 based on A cancer stages, B major subclasses, C patient age, D menopause status. *P < 0.05; **P < 0.01; ***P < 0.001.
Fig. 2 Expression pattern of highly deregulated WNTs in BC based on clinicopathological characteristics by UALCAN database. Expression pattern of WNT2, WNT7B, WNT11 based on A cancer stages, B major subclasses, C patient age, D menopause status. *P < 0.05; **P < 0.01; ***P < 0.001.CC BY · PubMed Central
Fig. 3 Pan-cancer analysis of highly deregulated WNTs utilizing TIMER2.0. A Expression levels of WNT2 in different tumors vs. corresponding controls. B Expression levels of WNT7B in different tumors vs. corresponding controls. C Expression levels of WNT11 in different tumors vs. corresponding controls. (*P < 0.05; **P < 0.01; ***P < 0.001)
Fig. 3 Pan-cancer analysis of highly deregulated WNTs utilizing TIMER2.0. A Expression levels of WNT2 in different tumors vs. corresponding controls. B Expression levels of WNT7B in different tumors vs. corresponding controls. C Expression levels of WNT11 in different tumors vs. corresponding controls. (*P < 0.05; **P < 0.01; ***P < 0.001)CC BY · PubMed Central
Fig. 4 Expression of WNTs correlates with survival outcomes in BC patient. KM plots showing the OS of A WNT2, B WNT7B, C WNT11. Red and black colors signify higher and lower expression groups.
Fig. 4 Expression of WNTs correlates with survival outcomes in BC patient. KM plots showing the OS of A WNT2, B WNT7B, C WNT11. Red and black colors signify higher and lower expression groups.CC BY · PubMed Central
Fig. 5 A Visualization of the most significant DEGs in GEO datasets. Scatterplots showing Spearman pairwise correlations between B WNT2 and WNT7B, C WNT2 and WNT11.
Fig. 5 A Visualization of the most significant DEGs in GEO datasets. Scatterplots showing Spearman pairwise correlations between B WNT2 and WNT7B, C WNT2 and WNT11.CC BY · PubMed Central
Fig. 6 Gene effect scores for A WNT2, B WNT7B, and C WNT11 in various breast cancer cell lines.
Fig. 6 Gene effect scores for A WNT2, B WNT7B, and C WNT11 in various breast cancer cell lines.CC BY · PubMed Central
Fig. 7 The methylation levels of A WNT2, B WNT7B, and C WNT11 between normal tissues and tumor tissues using the SMART database.
Fig. 7 The methylation levels of A WNT2, B WNT7B, and C WNT11 between normal tissues and tumor tissues using the SMART database.CC BY · PubMed Central
Fig. 8 The genetic alterations of WNT11 across the BRCA cohort were analysed by the cBioPortal database. A Alterations summary of WNT11 B The mutation types, number, and sites of the WNT11 genetic alterations. C 3D protein structure of WNT11 from AlphaFold.
Fig. 8 The genetic alterations of WNT11 across the BRCA cohort were analysed by the cBioPortal database. A Alterations summary of WNT11 B The mutation types, number, and sites of the WNT11 genetic alterations. C 3D protein structure of WNT11 from AlphaFold.CC BY · PubMed Central
Fig. 9 Visualization of typical patterns of A immune checkpoint genes, B immune inhibitors, C immune stimulators, D chemokines, E chemokine receptors among WNT2, WNT7B, and WNT11.
Fig. 9 Visualization of typical patterns of A immune checkpoint genes, B immune inhibitors, C immune stimulators, D chemokines, E chemokine receptors among WNT2, WNT7B, and WNT11.CC BY · PubMed Central
Fig. 10 Expression analysis of key WNTs from scRNA sequencing database. A expression of WNT2 in subgroups of immune cells. B expression of WNT7B in subgroups of immune cells. C expression of WNT11 in subgroups of immune cells. D Visualization of typical patterns of immune cells among WNT2, WNT7B, and WNT11.
Fig. 10 Expression analysis of key WNTs from scRNA sequencing database. A expression of WNT2 in subgroups of immune cells. B expression of WNT7B in subgroups of immune cells. C expression of WNT11 in subgroups of immune cells. D Visualization of typical patterns of immune cells among WNT2, WNT7B, and WNT11.CC BY · PubMed Central
Fig. 11 Key WNTs expression predicts drug sensitivity. The correlation between WNTs and 53 identified interacting genes and their drug sensitivity A by GDSC, B by CTRP. The correlation between WNT2 expression and the most significant drug sensitivity C by GDSC, D by CTRP. The correlation between WNT7B expression and the most significant drug sensitivity E by GDSC, F by CTRP. The correlation between WNT11 expression and the most significant drug sensitivity G by GDSC, H by CTRP.
Fig. 11 Key WNTs expression predicts drug sensitivity. The correlation between WNTs and 53 identified interacting genes and their drug sensitivity A by GDSC, B by CTRP. The correlation between WNT2 expression and the most significant drug sensitivity C by GDSC, D by CTRP. The correlation between WNT7B expression and the most significant drug sensitivity E by GDSC, F by CTRP. The correlation between WNT11 expression and the most significant drug sensitivity G by GDSC, H by CTRP.CC BY · PubMed Central
Fig. 12 Enrichment analysis of the related genes of WNT2, WNT7B, and WNT11. A KEGG pathway, B Reactome pathway, C GO-BP, D GO-CC, and E GO-MF analysis.
Fig. 12 Enrichment analysis of the related genes of WNT2, WNT7B, and WNT11. A KEGG pathway, B Reactome pathway, C GO-BP, D GO-CC, and E GO-MF analysis.CC BY · PubMed Central

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Cites

Research works printed but not linked: 2

  1. Current State of Breast Cancer Diagnosis, Treatment, and Theranostics. https://www.mdpi.com/1999-4923/13/5/723. · DOI · Paper page
  2. Miller, J. R. The Wnts. Genome Biol. 3, REVIEWS3001 (2002).

Metadata

Authors
Fariha, F. T. J., Fuad, M., Saha, C. S., Hossen, S., & Hossain, M. J.
Affiliations
Jagannath University (BD)
Corresponding author
Hossain, Md. Jubayer
ORCID
Hossain, Md. Jubayer
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2025-10-03
Volume
15
Issue
1
Pages
34490-34490
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-025-13315-6
PMC
PMC12494856
OpenAlex
W4414778764
Cited by
1
References
87
Citations by year
2025: 1
FWCI
0.30
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
Keywords
Wnt gene family, breast cancer, prognostic factors, Wnt2, Wnt7b, Wnt11, gene amplification, DNA methylation, immune cell infiltration, immunotherapy response, drug sensitivity, Wnt signaling, precision oncology
MeSH terms
Breast Neoplasms, Female, Humans, Prognosis, Biomarkers, Tumor, Gene Expression Regulation, Neoplastic, DNA Methylation, Computational Biology, Gene Expression Profiling, Wnt Proteins, Wnt2 Protein, Wnt Signaling Pathway

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