title: Elevated expression of the centromere protein-A(CENP-A)-encoding gene as a prognostic and predictive biomarker in human cancers.
abstract: Centromere protein-A (CENP-A), a histone-H3 variant, plays an essential role in cell division by ensuring proper formation and function of centromeres and kinetochores. Elevated CENP-A expression has been associated with cancer development. This study aimed to establish whether elevated CENP-A expression can be used as a prognostic and predictive cancer biomarker. Molecular profiling of CENP-A in human cancers was investigated using genomic, transcriptomic and patient information from databases, including COSMIC, Oncomine, Kaplan-Meier plotter and cBioPortal. A network of CENP-A co-expressed genes was derived from cBioPortal and analyzed using Ingenuity Pathway Analysis (IPA) and Oncomine protocols to explore the function of CENP-A and its predictive potential. Transcriptional and post-transcriptional regulation of CENP-A expression was analyzed in silico. It was found that CENP-A expression was elevated in 20 types of solid cancer compared with normal counterparts. Elevated CENP-A expression highly correlated with cancer progression and poor patient outcome. Genomic analysis indicated that the elevated CENP-A expression was not due to alterations in the sequence or copy number of the CENP-A gene. Furthermore, CENP-A can be regulated by key oncogenic proteins and tumor-suppressive microRNAs. CENP-A co-expression network analysis indicated that CENP-A function is associated with cell cycle progression. Oncomine analysis showed a strong correlation between elevated CENP-A expression and oncolytic response of breast cancer patients to taxane-based chemotherapy. In conclusion, elevated CENP-A expression is coupled to malignant progression of numerous types of cancer. It may be useful as a biomarker of poor patient prognosis and as a predictive biomarker for taxane-based chemotherapy.
authors.affiliation: Department of Pharmacology, School of Medicine, Shandong University, Jinan, Shandong, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Experimental Therapeutics, BC Cancer Research Centre, Vancouver, BC, Canada.|Interdisciplinary Oncology Program, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.|Faculty of Medicine, Université Laval, Québec, QC, Canada.
authors.forename: Pier-Luc
authors.initials: PL
authors.lastname: Clermont
authors.affiliation: Department of Pharmacology, School of Medicine, Shandong University, Jinan, Shandong, China.
authors.forename: Wenlin
authors.initials: W
authors.lastname: Jiao
authors.affiliation: Department of Experimental Therapeutics, BC Cancer Research Centre, Vancouver, BC, Canada.|Interdisciplinary Oncology Program, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.|Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Cheryl D
authors.initials: CD
authors.lastname: Helgason
authors.affiliation: Department of Experimental Therapeutics, BC Cancer Research Centre, Vancouver, BC, Canada.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Gout
authors.affiliation: Department of Experimental Therapeutics, BC Cancer Research Centre, Vancouver, BC, Canada.|Interdisciplinary Oncology Program, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.|Vancouver Prostate Center, Vancouver, BC, Canada.|Department of Urologic Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Yuzhuo
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Experimental Therapeutics, BC Cancer Research Centre, Vancouver, BC, Canada.|Interdisciplinary Oncology Program, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.|Vancouver Prostate Center, Vancouver, BC, Canada.
authors.forename: Sifeng
authors.initials: S
authors.lastname: Qu
mesh_terms: D001324:Autoantigens / Q000235:genetics*; D014408:Biomarkers, Tumor; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D030541:Databases, Genetic; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D053208:Kaplan-Meier Estimate; D009154:Mutation; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality*; D011379:Prognosis; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D001324:Autoantigens; D014408:Biomarkers, Tumor; C000619700:CENPA protein, human; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone
keywords: CENP-A; centromere protein-A; co-expression network; predictive biomarker; prognostic biomarker