Deciphering Circadian Rhythm–Related Molecular Subtypes in Breast Cancer and Establishing a Prognostic Prediction Model.

Background: Recent evidence suggests that alterations in circadian rhythm genes may lead to circadian rhythm disruption (CRD), which is a key mechanism in the progression of breast cancer. Therefore, investigating the role of circadian rhythm genes in the prognosis of breast cancer holds significant...

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Published in:BioMed Research International Vol. 2025; pp. 1 - 20
Main Authors: Lu, Yanzhen, Yang, Yunfei, Yu, Dan, Tan, Yuxi, Feng, Gang, Ouyang, Liquan, Tan, Lulu, Tan, Yuyan, Mohammadi, Saeed
Format: research tables/charts Journal Article
Published: Wiley-Blackwell 9/9/2025
Online Access:View this record in EBSCOhost
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      dt: 9/9/2025
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      pub: Wiley-Blackwell
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        atl: Deciphering Circadian Rhythm–Related Molecular Subtypes in Breast Cancer and Establishing a Prognostic Prediction Model.
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          Lu, Yanzhen
          Yang, Yunfei
          Yu, Dan
          Tan, Yuxi
          Feng, Gang
          Ouyang, Liquan
          Tan, Lulu
          Tan, Yuyan
          Mohammadi, Saeed
        affil: Department of Thyroid and Breast Surgery,, The First College of Clinical Medical Science,, China Three Gorges University & Yichang Central People's Hospital,, Yichang, Hubei,, China, ctgu.edu.cn
      sug:
        subj:
          Breast Neoplasms Prognosis
          Breast Neoplasms Familial and Genetic
          Breast Neoplasms Classification
          Circadian Rhythm
          Gene Expression Profiling
          Prediction Models
          Human
          Funding Source
          Female
          Adult
          Middle Age
          Cancer Patients
          Mutation
          Blood Glucose
          Penicillins
          Streptomycin
          Regression
          RNA, Messenger
          Factor Analysis
          Algorithms
          Wilcoxon Rank Sum Test
          Chi Square Test
          Cell Culture Techniques
          Descriptive Statistics
          Reverse Transcriptase Polymerase Chain Reaction
          Fibroblasts
          Chemotherapy, Cancer
          Immune Checkpoint Inhibitors
          Immunotherapy
          Adult: 19-44 years
          Middle Aged: 45-64 years
          Female
      ab: Background: Recent evidence suggests that alterations in circadian rhythm genes may lead to circadian rhythm disruption (CRD), which is a key mechanism in the progression of breast cancer. Therefore, investigating the role of circadian rhythm genes in the prognosis of breast cancer holds significant clinical value. Materials and Methods: We utilized expression profile data from the Gene Expression Omnibus (GEO) database to identify cancer features closely associated with CRD in breast cancer. Then, we analyzed publicly available datasets (including GEO, TCGA, and METABRIC) to identify alterations in core circadian genes significantly associated with patient survival across breast cancer and constructed a circadian‐related gene signature (CGS) based on these prognostic cancer features. Results: Circadian rhythm–related genes (CRGs) were selected to construct a risk gene signature associated with individual prognosis, which was validated in six independent cohorts and demonstrated good predictive ability. We identified three circadian rhythm–associated subtypes with distinct prognoses, which exhibited significant differences in immune checkpoint molecules, drug sensitivity, and molecular features. Additionally, the gene signature and clinicopathologic features were integrated to develop a risk model with enhanced predictive accuracy. To validate the functional role of signature genes, BMAL1 knockdown in SKBR3 cells disrupted circadian rhythms, with qPCR confirming altered risk gene expression. We found that the nomogram exhibited superior discriminative ability compared to the traditional breast cancer staging system. Conclusion: We developed a nomogram that can accurately predict the prognosis of breast cancer, and conclude that the expression of CRGs is crucial in breast cancer treatment decisions.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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