Ubiquitin‑like modifier‑activating enzyme 7 as a marker for the diagnosis and prognosis of breast cancer

Abstract

Ubiquitin-like modifier-activating enzyme 7 (UBA7) is a specific E1-like ubiquitin-activating enzyme involved in interferon-stimulated gene 15 (ISG15) conjugation. UBA7 expression has been reported to be notably decreased in lung cancer. The present study aimed to investigate the changes in UBA7 expression in breast cancer and the association between UBA7 expression and clinical characteristics, and to elucidate the diagnostic and prognostic significance of UBA7 in breast cancer. The clinical data and RNA-sequencing expression values of 1,104 patients with breast cancer were downloaded from The Cancer Genome Atlas database. The associations between UBA7 expression and clinical characteristics were determined using χ 2 and Fisher's exact tests. UBA7 expression values were divided into low and high groups using the optimal cutoff value, as determined by the overall survival (OS) value identified via a receiver operating characteristic (ROC) curve analysis, to further study the association between UBA7 expression and clinical characteristics. The diagnostic capability of UBA7 was assessed via ROC analysis, and Kaplan-Meier curve and Cox regression analyses were performed to determine the prognostic value of UBA7. The results demonstrated that UBA7 expression was decreased in breast cancer, and significant differences were observed between groups with regards to vital status, tumor classification, metastasis classification, histological type, sex, molecular subtype, and expression levels of progesterone receptor, estrogen receptor (ER) and human epidermal growth factor receptor 2. Low and high UBA7 expression levels were associated with age, ER expression, menopause status, Tumor-Node-Metastasis classification stage, margin status, vital status, radiation therapy use, OS and relapse-free survival. Furthermore, patients with low UBA7 expression levels had a poor prognosis. UBA7 expression also demonstrated an ability to diagnose patients at all clinical stages. Taken together, the results indicated that UBA7 expression was significantly decreased in breast cancer, and was associated with clinical characteristics and prognosis. Thus, UBA7 can be deemed as a potential biomarker in breast cancer, and may serve as a target in treatment.

Association of expression of epigenetic molecular factors with DNA methylation and sensitivity to chemotherapeutic agents in cancer cell lines

“…Examples of probe associations included ABC family transporters ABCC1 and ABCC3, SLC transporters SLC2A1, SLC4A7, SLC22A5, SLC25A22, SLC26A1, SLC39A11, SLC39A13, and SLC45A1, the oncogenes ABL1, ABL2, NF1, and RPTOR, the DUSP5 and DUSP14 kinase genes , RAD51L1 involved in homologous recombination repair [ 135 ], FTO and HDAC9 encoding epigenetic factors, IRAK2 , MAP3K14 , KIF3 , ubiquitin related genes NEURL3 and UBE2O, and NFIA encoding the tumor-promoting transcription factor nuclear factor IA [ 136 ] (Additional file 12 : Table S12). Associations of gene regions included the ERBB2 ( HER2 ) and NOTCH3 oncogenes , the tumor suppressor PHLDA1, CASP8 which plays a central role in apoptosis [ 118 , 122 ], the N-myc interactor NMI, PON2 , CAMKK2 , LIPG , the DUSP6 kinase gene, KIF12 , the E-cadherin gene CDH1, the histone acetyltransferase MYST1 ( KAT8 , or MOF ), ubiquitin related NDFIP2 and UBA7 [ 137 , 138 ], NR1D2 ( Rev-erbβ ) encoding a transcriptional repressor, RAP1GAP2 , RASEF , the glucocorticoid receptor gene NR3C1 , PPAP2C , and the SLC transporter genes SLC44A2 and PQLC3 ( SCL66A3 ) (Additional file 13 : Table S13) .…”

Ubiquitin-Like Modifier Activating Enzyme 1 as a Novel Diagnostic and Prognostic Indicator That Correlates With Ferroptosis and the Malignant Phenotypes of Liver Cancer Cells

“…For example, ubiquitin-like modifier activating enzyme 2 ( UBA2 ) induces the migration and invasion of gastric cancer cells ( 27 ). UBA7 serves as a potential biomarker for diagnostic and prognostic prediction in breast cancer ( 28 ). UBA1 , ubiquitin-like modifier activating enzyme 1, is required for the cellular response to DNA damage ( 29 ).…”

Suppression of Tumorigenicity 5 Ameliorates Tumor Characteristics of Invasive Breast Cancer Cells via ERK/JNK Pathway

“…Based on the status of estrogen receptor (ER), progesterone receptor (PR) and receptor tyrosine-protein kinase erbB-2 (HER2), breast cancer is classified as Luminal A, Luminal B, HER2-positive (HER2-E) and triple-negative breast cancer (TNBC) subtypes ( 3 ). Although the endocrine therapy is the preferred treatment and has a better therapeutic effect for hormone receptor-positive breast cancer, quite a few hormone receptor-positive patients will develop either primary or secondary drug resistance ( 4 ). Additionally, most metastatic breast tumor patients, such as patients with TNBC subtype, has poor prognosis and high recurrence rate ( 5 ).…”