Diagnostic and prognostic value of plasma and tissue ubiquitin‐like, containing PHD and RING finger domains 1 in breast cancer patients

Abstract

Ubiquitin-like, containing PHD and RING finger domains 1 (UHRF1) has been reported to play an important role in breast carcinogenesis. This work investigated the correlation of UHRF1 DNA level in plasma with clinical characteristics of breast cancer and its clinical significance in breast cancer diagnosis. The expression of UHRF1 in primary breast cancer tissue was examined by Western blot. The UHRF1 DNA levels in plasma and UHRF1 mRNA expression in tissues were determined by accurate real-time quantitative PCR. The associations of UHRF1 levels with clinical variables were evaluated using standard statistical methods. The UHRF1 DNA in plasma of 229 breast cancer patients showed higher expression than healthy controls, which showed high specificity up to 76.2% at a sensitivity of 79.2%, and was significantly associated with c-erbB2 positive status, cancer stage and lymph node metastasis. High UHRF1 DNA level in plasma was significantly associated with short progression-free survival. The UHRF1 DNA level in plasma is highly correlative with breast cancer and its status and stage, and may be a potential independent diagnostic and prognostic factor for both breast cancer and the survival of breast cancer patients. (Cancer Sci 2013; 104: 194-199) B reast cancer is the most common malignant disease in women. Its prevalence rate has exhibited a clear increase in China. Furthermore, the mortality rate of breast cancer has risen by 38.9% in the past 20 years.(1) Current prognostic criteria only poorly predict the metastasis risk for an individual breast cancer patient due to a lack of specific biomarkers.(2) Thus, new prognostic biomarkers are urgently needed to identify breast cancer patients and those at the highest risk for developing metastasis.Gene-expression signatures of human primary breast cancers have shown more accurate prediction than current prognostic criteria.(3,4) ubiquitin-like, containing PHD and RING finger domains 1 (UHRF1) is a newly discovered gene reported to have a function in maintaining DNA methylation by helping recruit DNA methyltransferase 1 (DNMT1) to hemimethylated DNA. Kim et al.(5) demonstrated its new role as a transcriptional corepressor in recruitment of histone methyltransferase G9a and other chromatin modifying enzymes to target promoters, and pointed out its dynamic regulation mode in cancer cells. The functional research of UHRF1 have made it a novel diagnostic marker in lung and bladder cancer.(6,7) Ubiquitinlike, containing PHD and RING finger domains 1-induced epigenetic changes, involving DNA methylation, histone modification, chromatin remodeling and recruitment of transcriptional complex on the breast cancer susceptibility gene 1 (BRCA1) promoter, are responsible for BRCA1 silencing in sporadic breast cancer.(8) These findings indicate that UHRF1 might play an important role in cancer development.Cancer patients generally exhibit an increasing amount of circulating DNA that comes from cancer tissues. (9)(10)(11) However, it is difficult to establish a unitary method for de...

UHRF1: The key regulator of epigenetics and molecular target for cancer therapeutics

“…14 Presence of high circulatory levels of UHRF1 DNA in blood samples of breast and gastric cancer patients underlined its importance to act as an independent diagnostic and prognostic marker. 15,16 Its easy detection in tissue samples and urine sediments of bladder cancer patients by immunohistochemistry and enzymelinked immunosorbent assay, respectively, also supports its diagnostic value. 17 The importance of UHRF1 as a potential cancer drug target emerged from several studies where knockdown or silencing of UHRF1 in cancer cells led to reduced proliferation and increased apoptosis.…”

Uhrf1 is indispensable for normal limb growth by regulating chondrocyte differentiation through specific gene expression

“…liver (Jacob et al, 2015), gut (Marjoram et al, 2015), brain (Murao et al, 2014) and immune responses (Obata et al, 2014). Moreover, Uhrf1 overexpression is associated with progression of various cancer types, including breast, pancreatic, bladder and colon (Abu-Alainin et al, 2016;Li et al, 2011;Sabatino et al, 2012;Yang et al, 2012); thus, Uhrf1 can serve as a molecular marker for these cancers (Geng et al, 2013;Unoki et al, 2009). DNA methylation in the promoter regions of various genes can be dysregulated by Uhrf1 overexpression and consequently cancer cell proliferation is facilitated.…”

Luteolin Induces Apoptosis in BE Colorectal Cancer Cells by Downregulating Calpain, UHRF1, and DNMT1 Expressions

“…Conversely, UHRF1 is regulated by other TSGs such as p53 and p73 (12). UHRF1 has been reported to be overexpressed in various cancers such as breast, bladder, kidney, lung, prostate, cervical, and pancreatic cancers, as well as in astrocytomas and glioblastoma (13)(14)(15)(16).…”