Computational Analyses Reveal Deregulated Clock Genes Associated with Breast Cancer Development in Night Shift Workers
Abstract
:1. Introduction
2. Results
2.1. Differential Expression Analyses in NHS Dataset Highlights a Panel of Deregulated Clock Genes in BC Samples Compared with Matching Non-Transformed Breast Tissues
2.2. Clock Gene Expression in PBMCs from Healthy Night Shift Workers Does Not Show Differential Rhythmicity Compared with Day Shift Workers
2.3. PER1, TEF, and CLOCK Genes as Novel Putative Biomarkers of Breast Cancer Susceptibility
2.4. Core Clock Gene Analyses in Single-Cell RNA-Seq Datasets Highlight Conserved Tissue-Specific Pattern of Expression
2.5. Functional Enrichment and miRNA Network Analyses Reveal the Involvement of Pivotal Pathways and Post-Transcriptional Regulators in Transformed and Non-Transformed Breast Tissues
3. Discussion
4. Materials and Methods
4.1. Dataset Repositories and Gene Expression Analyses
4.2. Graphical Representations and Functional Analyses of Candidate Clock Genes and BC Genes
4.3. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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n | % | |
---|---|---|
Cohort | ||
NHS I | 318 | 51.04 |
NHS II | 305 | 48.96 |
Diagnosis year | ||
Prior to 1990 | 11 | 1.77 |
1990–1999 | 304 | 48.80 |
2000–2011 | 308 | 49.44 |
Age at the diagnosis | ||
mean (SD) | 56.8 (10.8) | |
<50 | 173 | 27.77 |
50–59 | 210 | 33.71 |
60–69 | 141 | 22.63 |
>69 | 99 | 15.89 |
IHC Subtype | ||
Basal | 59 | 9.47 |
HER2+ | 24 | 3.85 |
Luminal A | 247 | 39.65 |
Luminal B | 187 | 30.02 |
Missing | 96 | 15.41 |
Unclassified | 10 | 1.61 |
Grade | ||
G 1 | 146 | 23.43 |
G 2 | 305 | 48.96 |
G 3 | 144 | 23.11 |
n.a. | 28 | 4.49 |
Stage | ||
S I | 384 | 61.64 |
S II | 185 | 29.70 |
S III | 48 | 7.70 |
S IV | 4 | 0.64 |
n.a. | 2 | 0.32 |
Surgery | ||
None | 1 | 0.16 |
Lumpectomy | 278 | 44.62 |
Mastectomy | 249 | 39.97 |
Unknown | 95 | 15.25 |
Treatment | ||
None | 19 | 3.05 |
Chemotherapy | 41 | 6.58 |
Radiotherapy | 25 | 4.01 |
Hormonal therapy | 83 | 13.32 |
Mixed | 379 | 60.83 |
Unknown | 76 | 12.20 |
Recurrence | ||
yes | 91 | 14.61 |
no | 532 | 85.39 |
GEO ID | Contributors | Platform | Normalization | Samples (H. sapiens) | Reference |
---|---|---|---|---|---|
GSE115577 | Tamimi RM et al. | Affymetrix HTA 2.0 | RMA | 1246 (623 NA, 623 BC) | [26] |
GSE122541 | Gamble K et al. | Illumina HT-12 4.0 | Custom | 44 (22 DS, 22 NS) | [41] |
GSE107537 | Kervezee L et al. | Affymetrix HT Clariom S | RMA | 103 (52 DO, 51 NO) | [42] |
GSE164641 | Marino N et al. | Illumina HiSeq 4000 | DESeq2 | 162 (91 AV, 71 HI) | [24] |
GSE166044 | Marino N et al. | Illumina NextSeq 500 | DESeq2 | 30 (15 HC, 15 SU) | [43] |
Study ID | Technology | Number of Cells | Type of Cells (H. Sapiens) | Reference |
---|---|---|---|---|
SCP1039 | Illumina NextSeq 500 | 100,064 | Surgically resected breast cancer tissue | [45] |
SCP1106 | Illumina NextSeq 500 | 24,271 | Surgically resected breast cancer tissue | [46] |
SCP1731 | Illumina HiSeq X Ten | 52,681 | Surgically resected normal breast tissue | [47] |
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Vivarelli, S.; Spatari, G.; Costa, C.; Giambò, F.; Fenga, C. Computational Analyses Reveal Deregulated Clock Genes Associated with Breast Cancer Development in Night Shift Workers. Int. J. Mol. Sci. 2024, 25, 8659. https://doi.org/10.3390/ijms25168659
Vivarelli S, Spatari G, Costa C, Giambò F, Fenga C. Computational Analyses Reveal Deregulated Clock Genes Associated with Breast Cancer Development in Night Shift Workers. International Journal of Molecular Sciences. 2024; 25(16):8659. https://doi.org/10.3390/ijms25168659
Chicago/Turabian StyleVivarelli, Silvia, Giovanna Spatari, Chiara Costa, Federica Giambò, and Concettina Fenga. 2024. "Computational Analyses Reveal Deregulated Clock Genes Associated with Breast Cancer Development in Night Shift Workers" International Journal of Molecular Sciences 25, no. 16: 8659. https://doi.org/10.3390/ijms25168659