PMID- 36428736 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20221214 IS - 2072-6694 (Print) IS - 2072-6694 (Electronic) IS - 2072-6694 (Linking) VI - 14 IP - 22 DP - 2022 Nov 17 TI - Mechanistic and Clinical Evidence Supports a Key Role for Cell Division Cycle Associated 5 (CDCA5) as an Independent Predictor of Outcome in Invasive Breast Cancer. LID - 10.3390/cancers14225643 [doi] LID - 5643 AB - BACKGROUND: Cell Division Cycle Associated 5 (CDCA5) plays a role in the phosphoinositide 3-kinase (PI3K)/AKT/mTOR signalling pathway involving cell division, cancer cell migration and apoptosis. This study aims to assess the prognostic and biological value of CDCA5 in breast cancer (BC). METHODS: The biological and prognostic value of CDCA5 were evaluated at mRNA (n = 5109) and protein levels (n = 614) utilizing multiple well-characterized early stage BC cohorts. The effects of CDCA5 knockdown (KD) on multiple oncogenic assays were assessed in vitro using a panel of BC cell lines. RESULTS: this study examined cohorts showed that high CDCA5 expression was correlated with features characteristic of aggressive behavior and poor prognosis, including the presence of high grade, large tumor size, lymphovascular invasion (LVI), hormone receptor negativity and HER2 positivity. High CDCA5 expression, at both mRNA and protein levels, was associated with shorter BC-specific survival independent of other variables (p = 0.034, Hazard ratio (HR) = 1.6, 95% CI; 1.1-2.3). In line with the clinical data, in vitro models indicated that CDCA5 depletion results in a marked decrease in BC cell invasion and migration abilities and a significant accumulation of the BC cells in the G2/M-phase. CONCLUSIONS: These results provide evidence that CDCA5 plays an important role in BC development and metastasis and could be used as a potential biomarker to predict disease progression in BC. FAU - Kariri, Yousif A AU - Kariri YA AUID- ORCID: 0000-0002-2507-2292 AD - Academic Unit for Translational Medical Sciences, School of Medicine, Biodiscovery Institute, University Park Campus, University of Nottingham, Nottingham NG7 2RD, UK. AD - Department of Clinical Laboratory Science, Faculty of Applied Medical Science, Shaqra University, Shaqra 11961, Saudi Arabia. AD - Nottingham Breast Cancer Research Centre, Nottingham NG7 2RD, UK. FAU - Joseph, Chitra AU - Joseph C AUID- ORCID: 0000-0003-2631-9266 AD - School of Medicine, Nottingham City Hospital, Nottingham University Hospitals NHS Trust and The University of Nottingham, Nottingham NG5 1PB, UK. FAU - Alsaleem, Mansour A AU - Alsaleem MA AUID- ORCID: 0000-0002-7689-2493 AD - Academic Unit for Translational Medical Sciences, School of Medicine, Biodiscovery Institute, University Park Campus, University of Nottingham, Nottingham NG7 2RD, UK. AD - Nottingham Breast Cancer Research Centre, Nottingham NG7 2RD, UK. AD - Department of Applied Medical Science, Applied College, Qassim University, Unayzah 56435, Saudi Arabia. FAU - Elsharawy, Khloud A AU - Elsharawy KA AD - Academic Unit for Translational Medical Sciences, School of Medicine, Biodiscovery Institute, University Park Campus, University of Nottingham, Nottingham NG7 2RD, UK. AD - Nottingham Breast Cancer Research Centre, Nottingham NG7 2RD, UK. AD - Department of Zoology, Faculty of Science, Damietta University, Damietta 34517, Egypt. FAU - Alsaeed, Sami AU - Alsaeed S AD - Academic Unit for Translational Medical Sciences, School of Medicine, Biodiscovery Institute, University Park Campus, University of Nottingham, Nottingham NG7 2RD, UK. AD - Nottingham Breast Cancer Research Centre, Nottingham NG7 2RD, UK. AD - Department of Clinical Laboratory Science, Faculty of Applied Medical Sciences, Northern Border University, Arar 73244, Saudi Arabia. FAU - Toss, Michael S AU - Toss MS AD - Nottingham Breast Cancer Research Centre, Nottingham NG7 2RD, UK. AD - School of Medicine, Nottingham City Hospital, Nottingham University Hospitals NHS Trust and The University of Nottingham, Nottingham NG5 1PB, UK. FAU - Mongan, Nigel P AU - Mongan NP AUID- ORCID: 0000-0001-5438-1126 AD - Biodiscovery Institute, Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Science, University of Nottingham, Nottingham NG7 2RD, UK. AD - Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA. FAU - Green, Andrew R AU - Green AR AUID- ORCID: 0000-0002-0488-5913 AD - Academic Unit for Translational Medical Sciences, School of Medicine, Biodiscovery Institute, University Park Campus, University of Nottingham, Nottingham NG7 2RD, UK. AD - Nottingham Breast Cancer Research Centre, Nottingham NG7 2RD, UK. FAU - Rakha, Emad A AU - Rakha EA AD - Academic Unit for Translational Medical Sciences, School of Medicine, Biodiscovery Institute, University Park Campus, University of Nottingham, Nottingham NG7 2RD, UK. AD - Nottingham Breast Cancer Research Centre, Nottingham NG7 2RD, UK. AD - School of Medicine, Nottingham City Hospital, Nottingham University Hospitals NHS Trust and The University of Nottingham, Nottingham NG5 1PB, UK. LA - eng PT - Journal Article DEP - 20221117 PL - Switzerland TA - Cancers (Basel) JT - Cancers JID - 101526829 PMC - PMC9688237 OTO - NOTNLM OT - CDCA5 OT - breast cancer OT - prognosis OT - progression COIS- The authors have no conflict of interest to declare. EDAT- 2022/11/27 06:00 MHDA- 2022/11/27 06:01 PMCR- 2022/11/17 CRDT- 2022/11/26 01:05 PHST- 2022/08/11 00:00 [received] PHST- 2022/11/12 00:00 [revised] PHST- 2022/11/15 00:00 [accepted] PHST- 2022/11/26 01:05 [entrez] PHST- 2022/11/27 06:00 [pubmed] PHST- 2022/11/27 06:01 [medline] PHST- 2022/11/17 00:00 [pmc-release] AID - cancers14225643 [pii] AID - cancers-14-05643 [pii] AID - 10.3390/cancers14225643 [doi] PST - epublish SO - Cancers (Basel). 2022 Nov 17;14(22):5643. doi: 10.3390/cancers14225643.