The Potential Prognostic Role of Oligosaccharide-Binding Fold-Containing Protein 2A (OBFC2A) in Triple-Negative Breast Cancer

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.

DNA‐dependent phase separation by human SSB2 (NABP1/OBFC2A) protein points to adaptations to eukaryotic genome repair processes

“…hSSB2 downregulation sensitizes cells for DNA damage, as evidenced by increased UV sensitivity, increased amounts cyclobutane pyrimidine dimer lesions, impaired RPA localization to DNA damage sites, and delayed recruitment of the XPC nucleotide excision repair protein upon UV irradiation (Boucher et al, 2021 ; Lawson et al, 2020 ). Furthermore, high hSSB2 expression was found to be associated with worse breast cancer prognosis, while downregulation of hSSB2 expression in triple‐negative breast cancer cells inhibited cell proliferation and migration and promoted apoptosis (Wu et al, 2021 ). In a specific case of acute promyelocytic leukemia, formation of a hSSB2‐RARA (retinoic acid receptor) chimera protein was linked to increased cancer predisposition (Won et al, 2013 ).…”

DNA-dependent phase separation by human SSB2 (NABP1/OBFC2A) protein points to adaptations to eukaryotic genome repair processes

“…hSSB2 downregulation sensitizes cells for DNA damage, as evidenced by increased UV sensitivity, increased amounts cyclobutane pyrimidine dimer lesions, impaired RPA localization to DNA damage sites, and delayed recruitment of the XPC nucleotide excision repair protein upon UV irradiation (14,27). Furthermore, high hSSB2 expression was found to be associated with worse breast cancer prognosis, while downregulation of hSSB2 expression in triple-negative breast cancer cells inhibited cell proliferation and migration and promoted apoptosis (57). In a specific case of acute promyelocytic leukemia, formation of a hSSB2-RARA (retinoic acid receptor) chimera protein was linked to increased cancer predisposition (58).…”

A novel ferroptosis‑related gene signature for overall survival prediction and immune infiltration in patients with breast cancer

“…Moreover, the gene expression and clinical information of 1,904 patients with breast cancer from the METABRIC database were downloaded from cBioPortal (https://www. cbioportal.org/) as previously reported (30), which was used as the validation cohort. FRGs were identified from the GeneCards database (https://www.genecards.org/), FerrDb database (http://www.zhounan.org/ferrdb/) and other related literature (31,32).…”

“…The expression profiling of FRGs and the corresponding clinical information of 327 patients with breast cancer, including their age, TNM stage and survival information, were obtained from the GSE20685 database ( https://www.ncbi.nlm.nih.gov/geo/ ) and used as the training cohort. Moreover, the gene expression and clinical information of 1,904 patients with breast cancer from the METABRIC database were downloaded from cBioPortal ( https://www.cbioportal.org/ ) as previously reported ( 30 ), which was used as the validation cohort. FRGs were identified from the GeneCards database ( https://www.genecards.org/ ), FerrDb database ( http://www.zhounan.org/ferrdb/ ) and other related literature ( 31 , 32 ).…”