The clinicopathological and prognostic significances of CDC73 expression in breast cancer: A pathological and bioinformatics analysis
Ying E1, Hang Xue1, Cong-Yu Zhang2, Ming-Zhen Zhao3 and Hua-Chuan Zheng1
1Department of Oncology and Center Laboratory, The Affiliated Hospital of Chengde Medical University, Chengde, China,
2Cancer Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China and
3Department of Respiratory Medicine, The Affiliated Hospital of Chengde Medical University, Chengde, China
Corresponding Author: Hua-chuan Zheng, Department of Oncology and Center Laboratory, The Affiliated Hospital of Chengde Medical University, Chengde 067000, PR China. email: zheng_huachuan@hotmail.com
Summary. 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 para-fibromin 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 triple-negative 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. Histol Histopathol 38, 453-465 (2023)
Key words: Breast cancer, Prognosis, Parafibromin, Pathobiological behaviors
DOI: 10.14670/HH-18-534
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ŠThe Author(s) 2023. Open Access. This article is licensed under a Creative Commons CC-BY International License. |
