Elevated expression of the centromere protein‐A(CENP‐A)‐encoding gene as a prognostic and predictive biomarker in human cancers

Sun, Xia; Clermont, Pier-Luc; Jiao, Wenlin; Helgason, Cheryl D.; Gout, Peter W.; Wang, Yuzhuo; Qu, Sifeng

doi:10.1002/ijc.30133

Cited by 90 publications

(101 citation statements)

References 51 publications

(90 reference statements)

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“…For all members of this gene family, the entire coding sequence is located in the last exon, and the sequence identity of encoded proteins reaches 50%‐68% . Cancer‐testis antigens (CTAs) are expressed in diverse histological types of malignant tumours, yet they are seldom expressed in normal somatic tissues except for immunoprivileged gametogenic tissues, which indicates a similarity between the gametogenesis and tumourigenesis processes . CTAs exhibit a strong immunogenicity and a specific expression pattern, making them a promising target .…”

Section: Discussionmentioning

confidence: 99%

“…16,17 Cancer-testis antigens (CTAs) are expressed in diverse histological types of malignant tumours, yet they are seldom expressed in normal somatic tissues except for immunoprivileged gametogenic tissues, which indicates a similarity between the gametogenesis and tumourigenesis processes. 18 CTAs exhibit a strong immunogenicity and a specific expression pattern, making them a promising target. 19 CTAs or peptides derived from CTAs can be used for cancer vaccination due to their immunogenicity.…”

Section: Discussionmentioning

confidence: 99%

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A four‐gene‐based prognostic model predicts overall survival in patients with hepatocellular carcinoma

Long

Zhang

Wan

et al. 2018

J Cellular Molecular Medi

130

124

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With the development of new advances in hepatocellular carcinoma (HCC) management and noninvasive radiological techniques, high‐risk patient groups such as those with hepatitis virus are closely monitored. HCC is increasingly diagnosed early, and treatment may be successful. In spite of this progress, most patients who undergo a hepatectomy will eventually relapse, and the outcomes of HCC patients remain unsatisfactory. In our study, we aimed to identify potential gene biomarkers based on RNA sequencing data to predict and improve HCC patient survival. The gene expression data and clinical information were acquired from The Cancer Genome Atlas (TCGA) database. A total of 339 differentially expressed genes (DEGs) were obtained between the HCC (n = 374) and normal tissues (n = 50). Four genes (CENPA, SPP1, MAGEB6 and HOXD9) were screened by univariate, Lasso and multivariate Cox regression analyses to develop the prognostic model. Further analysis revealed the independent prognostic capacity of the prognostic model in relation to other clinical characteristics. The receiver operating characteristic (ROC) curve analysis confirmed the good performance of the prognostic model. Then, the prognostic model and the expression levels of the four genes were validated using the Gene Expression Omnibus (GEO) dataset. A nomogram comprising the prognostic model to predict the overall survival was established, and internal validation in the TCGA cohort was performed. The predictive model and the nomogram will enable patients with HCC to be more accurately managed in trials testing new drugs and in clinical practice.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A four‐gene‐based prognostic model predicts overall survival in patients with hepatocellular carcinoma

Long

Zhang

Wan

et al. 2018

J Cellular Molecular Medi

130

124

View full text Add to dashboard Cite

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“…Among these, CENP-A and HJURP levels are elevated in human cancers, and both factors have been put forward as prognostic and predictive biomarkers Montes de Oca et al 2015;Sun et al 2016). The role of p53 in chromatin regulation has been emerging recently.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, loss of FOXM1 is associated with phenotypes reminiscent of CENP-A loss, such as mitotic catastrophe (Wonsey and Follettie 2005). Certain tumor growth-promoting genes and cancer down-regulated microRNAs have also been proposed recently to regulate CENP-A expression (Sun et al 2016). Identifying how these factors cooperate will be necessary to define the best combinatorial targeting approaches with the aim to prevent abnormal accumulation of centromeric factors in cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Essential role for centromeric factors following p53 loss and oncogenic transformation

et al. 2017

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In mammals, centromere definition involves the histone variant CENP-A (centromere protein A), deposited by its chaperone, HJURP (Holliday junction recognition protein). Alterations in this process impair chromosome segregation and genome stability, which are also compromised by p53 inactivation in cancer. Here we found that CENP-A and HJURP are transcriptionally up-regulated in p53-null human tumors. Using an established mouse embryonic fibroblast (MEF) model combining p53 inactivation with E1A or HRas-V12 oncogene expression, we reproduced a similar up-regulation of HJURP and CENP-A. We delineate functional CDE/CHR motifs within the Hjurp and Cenpa promoters and demonstrate their roles in p53-mediated repression. To assess the importance of HJURP up-regulation in transformed murine and human cells, we used a CRISPR/Cas9 approach. Remarkably, depletion of HJURP leads to distinct outcomes depending on their p53 status. Functional p53 elicits a cell cycle arrest response, whereas, in p53-null transformed cells, the absence of arrest enables the loss of HJURP to induce severe aneuploidy and, ultimately, apoptotic cell death. We thus tested the impact of HJURP depletion in pre-established allograft tumors in mice and revealed a major block of tumor progression in vivo. We discuss a model in which an "epigenetic addiction" to the HJURP chaperone represents an Achilles' heel in p53-deficient transformed cells.

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“…Increased levels of CENP-A are commonly reported in a range of aggressive cancers (Ma et al 2003;Tomonaga et al 2003;Li et al 2011;Qiu et al 2013;Gu et al 2014;Benito et al 2015;Sun et al 2016). The excess CENP-A can be incorporated both at the centromere and also in the chromosome arms (Fig.…”

Section: A Case Of Cellular Adaptability To Changes In Dosagementioning

confidence: 99%

Shaping Chromatin in the Nucleus: The Bricks and the Architects

Sitbon

Podsypanina

Yadav

et al. 2017

Cold Spring Harb Symp Quant Biol

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Chromatin organization in the nucleus provides a vast repertoire of information in addition to that encoded genetically. Understanding how this organization impacts genome stability and influences cell fate and tumorigenesis is an area of rapid progress. Considering the nucleosome, the fundamental unit of chromatin structure, the study of histone variants (the bricks) and their selective loading by histone chaperones (the architects) is particularly informative. Here, we report recent advances in understanding how relationships between histone variants and their chaperones contribute to tumorigenesis using cell lines and Xenopus development as model systems. In addition to their role in histone deposition, we also document interactions between histone chaperones and other chromatin factors that govern higher-order structure and control DNA metabolism. We highlight how a fine-tuned assembly line of bricks (H3.3 and CENP-A) and architects (HIRA, HJURP, and DAXX) is key in adaptation to developmental and pathological changes. An example of this conceptual advance is the exquisite sensitivity displayed by p53-null tumor cells to modulation of HJURP, the histone chaperone for CENP-A (CenH3 variant). We discuss how these findings open avenues for novel therapeutic paradigms in cancer care.

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Elevated expression of the centromere protein‐A(CENP‐A)‐encoding gene as a prognostic and predictive biomarker in human cancers

Cited by 90 publications

References 51 publications

A four‐gene‐based prognostic model predicts overall survival in patients with hepatocellular carcinoma

A four‐gene‐based prognostic model predicts overall survival in patients with hepatocellular carcinoma

Essential role for centromeric factors following p53 loss and oncogenic transformation

Shaping Chromatin in the Nucleus: The Bricks and the Architects

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