EccDNA-oriented ITGB7 expression in breast cancer

BACKGROUND: Extrachromosomal circular DNA (eccDNA) is omnipresent in cancers and related to the progression of tumors and oncogene amplification. However, its function in breast cancer (BC) is unclear. METHODS: After constructing the DNA library, CLeavage Effects by Circularization for In vitro Reporting of sequencing was performed for eccDNA detection using 1 BC tissue sample. Fastqc was used to evaluate the quality of the original data. Burrows-Wheeler-Alignment Tool was used to compare the original data to the reference genome. A Circle-MAP was subsequently performed to detect eccDNA, and Bedtools was used to annotate the eccDNA genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted by ClusterProfiler. The Genotype-Tissue Expression and the Cancer Genome Atlas databases were used to collect the ribonucleic acid–sequencing data of the BC and normal samples. A Gene Expression Profiling Interactive Analysis, the University of Alabama at Birmingham CANcer data analysis Portal, and Kaplan-Meier survival curves were used to analyze the Cancer Genome Atlas data. RESULTS: A total of 200 eccDNA genes, including IGTB7, were obtained. About the biological processes (BPs), these 200 genes were mainly enriched in actin cytoskeleton reorganization and axon guidance. Concerning the molecular functions (MFs), these 200 genes were mainly enriched in sodium ion transmembrane transporter activity and metal ion transmembrane transporter activity. As for cellular components (CCs), these 200 genes were mainly enriched in the transcription regulator complex and focal adhesion. ITGB7 was significantly enriched in cell-matrix adhesion and localization within the membrane in the BPs, integrin binding in the MFs, and cell-substrate junction and focal adhesion in the CCs. The 200 eccDNA genes were mainly enriched in the PI3K-Akt signaling pathway and focal adhesion. Notably, ITGB7 was enriched in focal adhesion, ECM-receptor interaction, the PI3K-Akt signaling pathway, and human papillomavirus infection. Besides, ITGB7 was significantly upregulated in BC patients and was associated with the menopause status of the BC patients. CONCLUSIONS: ITGB7 might serve as a prognostic marker for BC patients. ITGB7 has important implications for the individualized clinical treatment of BC patients.