Abstract
Breast cancer (BC) is one of the leading causes of cancer-related deaths in women. The purpose of this study is to identify key molecular markers related to the diagnosis and prognosis of early breast cancer (EBC). The data of mRNA, lncRNA and DNA methylation were downloaded from The Cancer Genome Atlas (TCGA) dataset for identification of differentially expressed mRNAs (DEmRNAs), differentially expressed lncRNAs (DElncRNAs) and DNA methylation analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyzes were used to identify the biological functions of DEmRNAs. The correlation analysis between DNA methylation and DEmRNAs was carried out. Then, diagnostic analysis and prognostic analysis of identified DEmRNAs and DElncRNAs were also performed in the TCGA database. Subsequently, methylation state verification for identified DEmRNAs was performed in the GSE32393 dataset. In addition, real-time polymerase chain reaction (RT-PCR) in vitro verification of genes was performed. Finally, AC093110.1 was overexpressed in human BC cell line MCF-7 to verify cell proliferation and migration. In this study, a total of 1633 DEmRNAs, 750 DElncRNAs and 8042 differentially methylated sites were obtained, respectively. In the Venn analysis, 11 keys DEmRNAs (ALDH1L1, SPTBN1, MRGPRF, CAV2, HSPB6, PITX1, WDR86, PENK, CACNA1H, ALDH1A2 and MME) were we found. ALDH1A2, ALDH1L1, HSPB6, MME, MRGPRF, PENK, PITX1, SPTBN1, WDR86 and CAV2 may be considered as potential diagnostic gene biomarkers in EBC. Strikingly, CAV2, MME, AC093110.1 and AC120498.6 were significantly actively correlated with survival. Methylation state of identified DEmRNAs in GSE32393 dataset was consistent with the result in TCGA. AC093110.1 can affect the proliferation and migration of MCF-7. ALDH1A2, ALDH1L1, HSPB6, MME, MRGPRF, PENK, PITX1, SPTBN1, WDR86 and CAV2 may be potential diagnostic gene biomarkers of EBC. Strikingly, CAV2, MME, AC093110.1 and AC120498.6 were significantly actively correlated with survival. The identification of these genes can help in the early diagnosis and treatment of EBC. In addition, AC093110.1 can regulate SPTBN1 expression and play an important role in cell proliferation and migration, which provides clues to clarify the regulatory mechanism of EBC.
Highlights
Breast cancer (BC) is one of the three most common cancers in the world[1]
Aldehyde dehydrogenase 1 family member A2 (ALDH1A2), Aldehyde dehydrogenase 1 family member L1 (ALDH1L1), HSPB6, Membrane metalloendopeptidase (MME), MRGPRF, PENK, PITX1, SPTBN1, WD repeat domain 86 (WDR86) and Caveolin 2 (CAV2) were considered as potential diagnostic gene biomarkers in early breast cancer (EBC)
AC093110.1 could regulate SPTBN1 expression and play an important role in cell proliferation and migration, which provides clues to clarify the regulatory mechanism of EBC
Summary
Breast cancer (BC) is one of the three most common cancers in the world[1]. BC is the second leading cause of cancer-related death in women, and its morbidity and mortality are expected to increase significantly in the few years[2,3]. Previous studies have found that Breast Cancer 1 protein (BRCA1) is a tumor suppressor, and decreased expression of BRCA1 disrupts breast differentiation and increases the risk of B C5. LncRNA small nucleolar RNA host gene 20 (SNHG20) may regulate human epidermal growth factor receptor 2 (HER2) through microRNA-495 (miR-495) and promote the proliferation, invasion and migration of BC c ells[10]. The decreased expression of breast cancer metastasis suppressor gene 1 (BRMS1) in triplenegative breast cancer (TNBC) is related to DNA methylation modification, and demethylation can reactivate BRMS1 expression to inhibit cell invasion[12]. Studies have found that the down-regulation of PAQR3 expression in BC tissues is significantly related to the abnormal methylation of the gene promoter[13]. We speculate that DNA methylation plays an important role in the progress of EBC
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
