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

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Titel: Comprehensive bioinformatics analysis reveals prognostic significance and immunological roles of WNT gene family in breast cancer.
Autoren: Fariha FTJ; Center for Health Innovation, Research, Action, and Learning-Bangladesh (CHIRAL Bangladesh), 100, Shukrabad, Mirpur Road, Dhanmondi, 1207, Dhaka, Bangladesh.; Big Bioinformatics Lab, Center for Health Innovation, Research, Action, and Learning-Bangladesh (CHIRAL Bangladesh), 100, Shukrabad, Mirpur Road, Dhanmondi, 1207, Dhaka, Bangladesh.; Department of Microbiology, Jagannath University, Dhaka, Bangladesh., Fuad M; Center for Health Innovation, Research, Action, and Learning-Bangladesh (CHIRAL Bangladesh), 100, Shukrabad, Mirpur Road, Dhanmondi, 1207, Dhaka, Bangladesh.; Big Bioinformatics Lab, Center for Health Innovation, Research, Action, and Learning-Bangladesh (CHIRAL Bangladesh), 100, Shukrabad, Mirpur Road, Dhanmondi, 1207, Dhaka, Bangladesh.; Department of Microbiology, Jagannath University, Dhaka, Bangladesh., Saha CS; Center for Health Innovation, Research, Action, and Learning-Bangladesh (CHIRAL Bangladesh), 100, Shukrabad, Mirpur Road, Dhanmondi, 1207, Dhaka, Bangladesh.; Big Bioinformatics Lab, Center for Health Innovation, Research, Action, and Learning-Bangladesh (CHIRAL Bangladesh), 100, Shukrabad, Mirpur Road, Dhanmondi, 1207, Dhaka, Bangladesh.; Department of Microbiology, Jagannath University, Dhaka, Bangladesh., Hossen S; Center for Health Innovation, Research, Action, and Learning-Bangladesh (CHIRAL Bangladesh), 100, Shukrabad, Mirpur Road, Dhanmondi, 1207, Dhaka, Bangladesh.; Big Bioinformatics Lab, Center for Health Innovation, Research, Action, and Learning-Bangladesh (CHIRAL Bangladesh), 100, Shukrabad, Mirpur Road, Dhanmondi, 1207, Dhaka, Bangladesh.; Department of Microbiology, Jagannath University, Dhaka, Bangladesh., Hossain MJ; Center for Health Innovation, Research, Action, and Learning-Bangladesh (CHIRAL Bangladesh), 100, Shukrabad, Mirpur Road, Dhanmondi, 1207, Dhaka, Bangladesh. contact.jubayerhossain@gmail.com.; Big Bioinformatics Lab, Center for Health Innovation, Research, Action, and Learning-Bangladesh (CHIRAL Bangladesh), 100, Shukrabad, Mirpur Road, Dhanmondi, 1207, Dhaka, Bangladesh. contact.jubayerhossain@gmail.com.; Department of Microbiology, Jagannath University, Dhaka, Bangladesh. contact.jubayerhossain@gmail.com.
Quelle: Scientific reports [Sci Rep] 2025 Oct 03; Vol. 15 (1), pp. 34490. Date of Electronic Publication: 2025 Oct 03.
Publikationsart: Journal Article
Sprache: English
Info zur Zeitschrift: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
Imprint Name(s): Original Publication: London : Nature Publishing Group, copyright 2011-
MeSH-Schlagworte: Breast Neoplasms*/genetics , Breast Neoplasms*/immunology , Breast Neoplasms*/mortality , Breast Neoplasms*/pathology , Wnt Proteins*/genetics , Wnt Proteins*/metabolism , Wnt Proteins*/immunology , Computational Biology*/methods, Humans ; Female ; Prognosis ; Gene Expression Regulation, Neoplastic ; Biomarkers, Tumor/genetics ; Wnt Signaling Pathway ; DNA Methylation ; Wnt2 Protein/genetics ; Gene Expression Profiling
Abstract: Competing Interests: Declarations. Consent for publication: The authors declare that they have no competing financial interests or personal relationships that could influence the publication of this study. Competing interests: The authors declare no competing interests.
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.
(© 2025. The Author(s).)
References: Cell. 2009 Mar 6;136(5):823-37. (PMID: 19269363)
Nature. 2021 Aug;596(7873):583-589. (PMID: 34265844)
Front Immunol. 2019 Aug 02;10:1835. (PMID: 31428105)
Mol Cell Biochem. 2021 Sep;476(9):3513-3536. (PMID: 33999334)
Acta Pharmacol Sin. 2012 Mar;33(3):351-62. (PMID: 22266725)
Cancer Med. 2023 May;12(10):11149-11165. (PMID: 36807772)
Clin Cancer Res. 2021 Sep 1;27(17):4669-4679. (PMID: 33827891)
Front Cell Dev Biol. 2021 Jun 11;9:676342. (PMID: 34179005)
Trends Cancer. 2021 Jun;7(6):525-540. (PMID: 33358111)
Expert Rev Mol Diagn. 2009 Jul;9(5):423-40. (PMID: 19580428)
BMC Cancer. 2022 Jul 19;22(1):790. (PMID: 35850748)
Commun Integr Biol. 2012 Sep 1;5(5):506-7. (PMID: 23739683)
Imeta. 2024 Feb 14;3(1):e177. (PMID: 38868514)
Cell Rep. 2021 May 4;35(5):109071. (PMID: 33951424)
Front Immunol. 2019 Dec 16;10:2872. (PMID: 31921137)
Nat Rev Cancer. 2025 Jan;25(1):59-73. (PMID: 39468210)
Cold Spring Harb Perspect Biol. 2013 Dec 01;5(12):a016949. (PMID: 24296170)
Organogenesis. 2011 Jul-Sep;7(3):202-8. (PMID: 22041517)
Nano Lett. 2021 May 26;21(10):4231-4240. (PMID: 33998789)
Int J Clin Exp Pathol. 2018 Sep 01;11(9):4552-4561. (PMID: 31949853)
Innovation (Camb). 2021 Jul 01;2(3):100141. (PMID: 34557778)
CA Cancer J Clin. 2024 May-Jun;74(3):229-263. (PMID: 38572751)
Nucleic Acids Res. 2023 Jan 6;51(D1):D1425-D1431. (PMID: 36321662)
Int J Mol Sci. 2023 Mar 10;24(6):. (PMID: 36982422)
Epigenetics Chromatin. 2019 Dec 5;12(1):71. (PMID: 31805986)
Breast. 2015 Oct;24(5):548-55. (PMID: 26187798)
Nat Rev Cancer. 2023 Jul;23(7):450-473. (PMID: 37217781)
Nucleic Acids Res. 2025 Jan 6;53(D1):D672-D677. (PMID: 39417505)
Genome Biol. 2014;15(12):550. (PMID: 25516281)
Mol Cancer. 2022 Jul 14;21(1):144. (PMID: 35836256)
Int J Cell Biol. 2023 Sep 21;2023:9296092. (PMID: 37780577)
Pharmaceutics. 2021 May 14;13(5):. (PMID: 34069059)
Biomolecules. 2023 Mar 06;13(3):. (PMID: 36979418)
Adv Anat Pathol. 2010 Jan;17(1):42-8. (PMID: 20032638)
Cancers (Basel). 2022 May 23;14(10):. (PMID: 35626173)
Cell Death Dis. 2019 Apr 11;10(4):327. (PMID: 30975976)
Immunol Rev. 2019 May;289(1):205-231. (PMID: 30977203)
PLoS One. 2009 Nov 23;4(11):e7965. (PMID: 19956757)
Clin Breast Cancer. 2020 Oct;20(5):361-370. (PMID: 32416986)
Cancer Res. 2023 Dec 1;83(23):3861-3867. (PMID: 37668528)
BMC Cancer. 2021 Feb 19;21(1):180. (PMID: 33607955)
Nucleic Acids Res. 2019 Jul 2;47(W1):W556-W560. (PMID: 31114875)
Nat Biotechnol. 2020 Jun;38(6):675-678. (PMID: 32444850)
ACS Nano. 2018 Sep 25;12(9):8977-8993. (PMID: 30133260)
Front Immunol. 2019 Dec 20;10:2854. (PMID: 31921125)
Front Nutr. 2022 Mar 14;9:847920. (PMID: 35360680)
Acta Biochim Pol. 2023 Apr 17;70(2):261-269. (PMID: 37331014)
Cell Biol Int. 2022 Jun;46(6):863-877. (PMID: 35297539)
Curr Opin Genet Dev. 2004 Feb;14(1):11-6. (PMID: 15108799)
Nucleic Acids Res. 2023 Jan 6;51(D1):D638-D646. (PMID: 36370105)
Mol Neurobiol. 2025 Mar;62(3):3630-3652. (PMID: 39313658)
Genome Res. 2003 Nov;13(11):2498-504. (PMID: 14597658)
Cancers (Basel). 2019 Jun 28;11(7):. (PMID: 31261718)
Oncol Res. 2021 Mar 16;28(6):661-674. (PMID: 32998794)
Cancers (Basel). 2021 Dec 10;13(24):. (PMID: 34944834)
Biochim Biophys Acta. 2012 Dec;1826(2):272-96. (PMID: 22579961)
Nat Rev Cancer. 2021 Jan;21(1):5-21. (PMID: 33097916)
Bioinformatics. 2018 Nov 1;34(21):3771-3772. (PMID: 29790900)
Cancer Res. 2022 Jul 5;82(13):2329-2343. (PMID: 35363853)
Cancer Sci. 2018 Nov;109(11):3368-3375. (PMID: 30137666)
Cell Cycle. 2012 Nov 1;11(21):4020-32. (PMID: 22992620)
Oncogene. 2017 Mar;36(11):1461-1473. (PMID: 27617575)
BMC Bioinformatics. 2023 Dec 17;24(1):483. (PMID: 38105215)
Genome Biol. 2002;3(1):REVIEWS3001. (PMID: 11806834)
Biomol Concepts. 2013 Dec;4(6):567-82. (PMID: 25436757)
Int J Mol Sci. 2012;13(2):1886-1918. (PMID: 22408430)
Cancers (Basel). 2020 Nov 15;12(11):. (PMID: 33203154)
Wiley Interdiscip Rev Syst Biol Med. 2018 Sep;10(5):e1422. (PMID: 29600540)
Mol Cancer. 2020 Nov 24;19(1):165. (PMID: 33234169)
Front Immunol. 2024 Feb 15;15:1367875. (PMID: 38426109)
Cancers (Basel). 2022 Apr 10;14(8):. (PMID: 35454818)
Neoplasia. 2022 Mar;25:18-27. (PMID: 35078134)
Ibrain. 2023 Sep 06;9(3):316-325. (PMID: 37786762)
Mol Biosyst. 2016 Feb;12(2):477-9. (PMID: 26661513)
J Med Internet Res. 2021 Jul 26;23(7):e27633. (PMID: 34309564)
Nucleic Acids Res. 2020 Jul 2;48(W1):W509-W514. (PMID: 32442275)
Adv Genet. 2010;70:27-56. (PMID: 20920744)
Contributed Indexing: Keywords: Bioinformatics; Breast cancer; Cancer treatment; Expression patterns; Immunology; Prognostic biomarkers; WNTs
Substance Nomenclature: 0 (Wnt Proteins)
0 (Biomarkers, Tumor)
0 (Wnt2 Protein)
Entry Date(s): Date Created: 20251003 Date Completed: 20251003 Latest Revision: 20251007
Update Code: 20251007
PubMed Central ID: PMC12494856
DOI: 10.1038/s41598-025-13315-6
PMID: 41044153
Datenbank: MEDLINE
Beschreibung
Abstract:Competing Interests: Declarations. Consent for publication: The authors declare that they have no competing financial interests or personal relationships that could influence the publication of this study. Competing interests: The authors declare no competing interests.<br />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.<br /> (© 2025. The Author(s).)
ISSN:2045-2322
DOI:10.1038/s41598-025-13315-6