Publication: The clinicopathological and prognostic significances of CDC73 expression in breast cancer: A pathological and bioinformatics analysis
Authors
E, Ying ; Xue, Hang ; Zhang, Cong Yu ; Zhao, Ming Zhen ; Zheng, Hua-Chuan
item.page.secondaryauthor
item.page.director
Publisher
Universidad de Murcia, Departamento de Biologia Celular e Histiologia
publication.page.editor
publication.page.department
DOI
https://doi.org/10.14670/HH-18-534
item.page.type
info:eu-repo/semantics/article
Description
Abstract
Parafibromin is a protein encoded by the
oncosuppressor CDC73 gene, whose mutation results in
hyperparathyroidism-jaw tumor syndrome (HPT-JT) and
parathyroid carcinoma. Down-regulation of parafibromin is linked to lung, gastric, colorectal, and
ovarian cancer tumorigenesis. Parafibromin expression
was detected by RT-PCR, bioinformatics analysis,
Western blot, and immunohistochemistry; and compared
with clinicopathological characteristics of breast cancer.
CDC73-related genes and pathways were analyzed using
bioinformatics analysis. Parafibromin expression was
increased in breast cancer compared to normal tissues at
both mRNA and protein levels (p<0.05). Among triplenegative breast cancers, it was higher in basal-like 1 than
basal-like 2 patients (p<0.05) and mesenchymal than
immunomodulatory patients (p<0.05). CDC73 mRNA
expression was positively correlated with white race,
non-infiltrating immune cells, favorable luminal
subtypes of PAM50, and prognosis of breast cancer
patients (p<0.05). The differential genes of CDC73 were
classified into enzyme inhibitors, peptidase, and
keratinization by KEGG (p<0.05). Similarly, it was
classified into ribosomes, TGF-β, oxidation
phosphorylation, inositol phosphate metabolism,
arachidonic acid metabolism, linoleic acid metabolism,
ERBB, and VEGF signaling pathways by GSEA
(p<0.05). The positively-correlated genes of CDC73
were involved in cell mobility, response to interferon α,
nuclear pore and basket, and histone methyltransferase.
The negatively-correlated genes of CDC73 were
involved in the mitochondrial respiratory chain,
thermogenesis, and ribosomes. Parafibromin expression
was higher in invasive ductal than lobular carcinoma
(p<0.05) and mucinous adenocarcinoma than others
(p<0.05). Parafibromin immunoreactivity as an
independent factor was positively associated with an
increased overall survival rate of breast cancer patients
(p<0.05). These findings suggest that up-regulation of
parafibromin in breast cancer patients is closely linked to
a favorable prognosis. It is involved in tumorigenesis
and subsequent progression by regulating metabolism,
ribosomes, and cytokines.
publication.page.subject
Citation
Histology and Histopathology Vol. 38, nº4 (2023)
item.page.embargo
Ir a Estadísticas
Este ítem está sujeto a una licencia Creative Commons. http://creativecommons.org/licenses/by-nc-nd/4.0/