ArticleCell cycle (Georgetown, Tex.)2014
Loss of circadian clock gene expression is associated with tumor progression in breast cancer.
Article in Cell cycle (Georgetown, Tex.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
142 citing papers in PubMed, 232 citations in OpenAlex.
- Functional deficiency of circadian regulator PER2 enhances breast cancer susceptibility and progression with immunosuppression.Oncogene · 2026Article
- In vivo CRISPR screening links NFKB1 to endocrine resistance in ER+ breast cancer.Endocrine-related cancer · 2026Article
- Circadian clock control of breast cancer hallmarks: molecular mechanisms and therapeutic implications.Cancer metastasis reviews · 2026Review
- Circadian-driven transcriptional programs govern metastatic progression.Cancer biology & medicine · 2026Review
- Metastasis in biological time.Frontiers in cell and developmental biology · 2026Review
- Circadian clock and cancer.Military Medical Research · 2026Review
- A signature constructed with circadian rhythm-related genes to predict the prognosis and therapy response for low-grade gliomas.Discover oncology · 2025Article
- Night shift work and breast cancer: from etiopathology to precision risk analysis.NPJ breast cancer · 2025Review
- LILRB4 regulates circadian disruption-induced mammary tumorigenesis via non-canonical WNT signaling pathway.Oncogene · 2025Article
- Targeting Cryptochromes in Chronic Diseases.Cell biology international · 2025Review
- CLOCK-mediated acetylation of NF-κB p65 drives immune evasion in breast cancer.Biology direct · 2025Article
- Casein kinase 1 family member CSNK1E can regulate proliferation and migration in hepatocellular carcinoma.Journal of cancer research and clinical oncology · 2025Article
- Integrating neuroscience and oncology: neuroimmune crosstalk in the initiation and progression of digestive system tumors.Molecular cancer · 2025Review
- High PER1 expression is associated with STK11 mutation and clinical biomarkers of immunotherapy resistance in lung adenocarcinoma.Journal of cancer research and clinical oncology · 2025Article
- Rhythm is essential: Unraveling the relation between the circadian clock and cancer.Critical reviews in oncology/hematology · 2025Review
- The role of cryptochrome (CRY) in cancer: molecular mechanisms and clock-based therapeutic strategies.Acta biochimica et biophysica Sinica · 2025Review
- Transcription of Clock Genes in Medulloblastoma.Cancers · 2025Article
- Neuroscience of cancer: unraveling the complex interplay between the nervous system, the tumor and the tumor immune microenvironment.Molecular cancer · 2025Review
- A Circadian Rhythm-related Signature to Predict Prognosis, Immune Infiltration, and Drug Response in Breast Cancer.Current medicinal chemistry · 2025Article
- Diurnal Variation of 8-hydroxy-2'-deoxyguanosine in Continuous Time Series of Two Breast Cancer Survivors.Journal of circadian rhythms · 2025Article
82 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Several studies suggest a link between circadian rhythm disturbances and tumorigenesis. However, the association between circadian clock genes and prognosis in breast cancer has not been systematically studied. Therefore, we examined the expression of 17 clock components in tumors from 766 node-negative breast cancer patients that were untreated in both neoadjuvant and adjuvant settings. In addition, their association with metastasis-free survival (MFS) and correlation to clinicopathological parameters were investigated. Aiming to estimate functionality of the clockwork, we studied clock gene expression relationships by correlation analysis. Higher expression of several clock genes (e.g., CLOCK, PER1, PER2, PER3, CRY2, NPAS2 and RORC) was found to be associated with longer MFS in univariate Cox regression analyses (HR<1 and FDR-adjusted P < 0.05). Stratification according to molecular subtype revealed prognostic relevance for PER1, PER3, CRY2 and NFIL3 in the ER+/HER2- subgroup, CLOCK and NPAS2 in the ER-/HER2- subtype, and ARNTL2 in HER2+ breast cancer. In the multivariate Cox model, only PER3 (HR = 0.66; P = 0.016) and RORC (HR = 0.42; P = 0.003) were found to be associated with survival outcome independent of established clinicopathological parameters. Pairwise correlations between functionally-related clock genes (e.g., PER2-PER3 and CRY2-PER3) were stronger in ER+, HER2- and low-grade carcinomas; whereas, weaker correlation coefficients were observed in ER- and HER2+ tumors, high-grade tumors and tumors that progressed to metastatic disease. In conclusion, loss of clock genes is associated with worse prognosis in breast cancer. Coordinated co-expression of clock genes, indicative of a functional circadian clock, is maintained in ER+, HER2-, low grade and non-metastasizing tumors but is compromised in more aggressive carcinomas.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.