RESUMO
BACKGROUND: To date, breast cancer remains the most common malignant tumor in women. In recent years, a growing number of studies on polycomb proteins have been conducted. The Ring finger protein1 (RING1), an essential component of the polycomb family of proteins, plays vital roles in the tumorigenesis of various cancer types. However, further research is required in determining RING1 expression and prognostic value in breast cancer. METHOD: RING1 expression level in multiple cancer types was evaluated using the XENA and UALCAN databases. Real-time quantitative PCR (real-time qPCR) and immunohistochemistry (IHC) were used to confirm this expression. The prognostic value was analyzed using our follow-up data and the Kaplan-Meier plotter website. RING1 co-expressed genes and its promoter methylation level were calculated using the cBioPortal and UALCAN online tools. The gene ontology (GO) and the Kyoto encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analyzed using the DAVID online analysis tool. RESULT: RING1 expression was upregulated in CHOL (Bile Duct Cancer), ESCA (Esophageal Cancer), LIHC (Liver Cancer), and PCPG (Pheochromocytoma & Paraganglioma). However, its expression level was decreased in COAD (Colon Cancer), KICH (Kidney Chromophobe), KIRP (kidney papillary cell carcinoma), THCA (Thyroid Cancer), and BRCA (Breast carcinoma). RING1 low expression is an unfavorable prognostic factor in many cancer patients, especially in breast cancer patients. For breast cancer, the IHC result showed that RING1 protein expression significantly and negatively correlates with tumor size (P = 0.029), LNM (P = 0.017), TNM stage (P = 0.016), ER (P = 0.005), Ki67 (P = 0.015), and p53 status (P = 0.034). Moreover, the multivariate Cox regression model indicated that RING1 (P = 0.038) and ER (P = 0.029) expressions were independent prognostic markers for breast cancer. RING1 co-expressed genes were selected and included HDAC10, PIN1, CDK3, BAX, and BAD. GO analysis and KEGG pathway analyses revealed that RING1 related genes, were mainly enriched in "regulation of transcription", "apoptotic process", "protein transport", "protein binding", "Notch signaling pathway", and "Homologous recombination". CONCLUSION: RING1 expression was downregulated in breast cancer, and its low expression was associated with worse disease outcomes. RING1 may act as a new prognostic biomarker for breast cancer.
RESUMO
OBJECTIVES: Breast malignancy is a serious threat to women's health around the world. Following the rapid progress in the field of cancer diagnostics and identification of pathological markers, breast tumor treatment methods have been greatly improved. However, for invasive, ductal carcinomas and mammary fibroadenoma, there is an urgent demand for better breast tumor-linked biomarkers. The current study was designed to identify diagnostic and/or therapeutic protein biomarkers for breast tumors. METHODS: A total of 140 individuals were included, comprising 35 healthy women, 35 invasive breast cancers (IBC), 35 breast ductal carcinomas in situ (DCIS), and 35 breast fibroadenoma patients. Isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis was employed to characterize differentially expressed proteins for potential biomarkers in IBC, DCIS, and fibroadenomas by comparisons with their matched adjacent tissues and/or normal breast tissues. The public databases Metascape and String were used for bioinformatic analyses. RESULTS: Using the proteomics approach, we identified differentially expressed proteins in tissues of different breast tumors compared to normal/adjacent breast tissues, including 100 in IBC, 52 in DCIS, and 44 in fibroadenoma. Among the 100 IBC differentially expressed proteins, 37 were found to be specific to this type of cancer only. Additionally, four proteins were specifically expressed in DCIS and four in fibroadenoma. Compared to corresponding adjacent tissues and normal breast tissues, 18 step-changing proteins were differentially expressed in IBC, 14 in DCIS, and 13 in fibroadenoma, respectively. Compared to DCIS and normal breast tissues, 65 proteins were differentially expressed in IBC with growing levels of malignancy. CONCLUSIONS: The identified potential protein biomarkers may be used as diagnostic and/or therapeutic targets in breast tumors.