Abstract
BackgroundPatients with triple-negative breast cancer (TNBC) have poor overall survival. The present study aimed to investigate the potential prognostics of TNBC by analyzing breast cancer proteomic and transcriptomic datasets.MethodsCandidate proteins selected from CPTAC (the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium) were validated using datasets from METABRIC (Molecular Taxonomy of Breast Cancer International Consortium). Kaplan-Meier analysis and ROC (receiver operating characteristic) curve analysis were performed to explore the prognosis of candidate genes. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis were performed on the suspected candidate genes. Single-cell RNA-seq (scRNA-seq) data from GSE118389 were used to analyze the cell clusters in which OBFC2A (Oligosaccharide-Binding Fold-Containing Protein 2A) was mainly distributed. TIMER (Tumor Immune Estimation Resource) was used to verify the correlation between OBFC2A expression and immune infiltration. Clone formation assays and wound healing assays were used to detect the role of OBFC2A expression on the proliferation, invasion, and migration of breast cancer cells. Flow cytometry was used to analyze the effects of silencing OBFC2A on breast cancer cell cycle and apoptosis.ResultsSix candidate proteins were found to be differentially expressed in non-TNBC and TNBC groups from CPTAC. However, only OBFC2A was identified as an independently poor prognostic gene marker in METABRIC (HR=3.658, 1.881-7.114). And OBFC2A was associated with immune functions in breast cancer. Biological functional experiments showed that OBFC2A might promote the proliferation and migration of breast cancer cells. The inhibition of OBFC2A expression blocked the cell cycle in G1 phase and inhibited the transformation from G1 phase to S phase. Finally, downregulation of OBFC2A also increased the total apoptosis rate of cells.ConclusionOn this basis, OBFC2A may be a potential prognostic biomarker for TNBC.
Highlights
Breast cancer has the highest incidence of malignant tumors among women worldwide, posing a serious threat to their health [1]
Oligosaccharide-Binding FoldContaining Protein 2A (OBFC2A) Is Upregulated in High-Grade Breast Cancer: A Potential Marker for triple-negative breast cancer (TNBC)
The results showed that the expression levels of OBFC2A were higher in the TNBC group than in the other subtypes, in both CPTAC and METABRIC (Figures 1A, C)
Summary
Breast cancer has the highest incidence of malignant tumors among women worldwide, posing a serious threat to their health [1]. More than 90% of basal-like breast cancers represent TNBC (triple-negative breast cancer), and basal-like breast cancer is the most common type of TNBC [3]. Existing studies have shown that the specific mechanism of TNBC is not clear. TNBC tumors tend to be more aggressive and larger, with higher oncology grades and lymph node metastasis. Due to the lack of clear molecular targets, the drug treatment of TNBC depends on chemotherapy. Compared with other breast cancer subtypes, TNBC patients have a higher long-term recurrence rate and poor prognosis [4]. New prognostic factors and therapeutic targets for TNBC need to be explored. Patients with triple-negative breast cancer (TNBC) have poor overall survival. The present study aimed to investigate the potential prognostics of TNBC by analyzing breast cancer proteomic and transcriptomic datasets
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