Association with clinicopathological characteristics

Excision repair cross complementing 1 (ERCC1), ribonucleotide reductase M1 (RRM1), b-tubulin III (TUBB3), thymidylate synthetase (TYMS), and topoisomerase IIa (TOP2A) genes have been shown to be associated with the pathogenesis and prognosis of various types of carcinomas; however, their roles in breast cancer have not been fully validated. In this study, we evaluated the correlations among these biomarkers and the associations between their expression intensity and the clinicopathological characteristics to investigate whether the above genes are underlying biomarkers for patients with breast cancer. Ninety-seven tissue specimens collected from breast cancer patients. The expression levels of these biomarkers were measured by the multiplex branched DNA liquidchip (MBL) technology and clinicopathological characteristics were collected simultaneously. The expression levels of ERCC1, TUBB3, TYMS, and TOP2Awere significantly associated with the characteristics of menopausal status, tumor size, lymph nodemetastasis, hormone receptor status, triple-negative status, Ki-67 index, and epidermal growth factor receptor. The expression intensity of ERCC1 negatively associated with that of TUBB3 and TYMS, and positively associated with that of RRM1. The expression intensity of TOP2A positively associated with that of TYMS. Hierarchical clustering analysis and difference test indicated that breast cancer with higher levels of TUBB3, TYMS, and TOP2A, as well as lower levels of ERCC1 andRRM1 tended to have higher histological grade and Ki-67 index. Our studies showed that ERCC1, TYMS, TUBB3, and TOP2A may be potential biomarkers for prognosis and individualized chemotherapy guidance, while there may be interactions between ERCC1 and RRM1, or TUBB3, or TYMS, as well as between TOP2A and TYMS in pathogenesis and development of breast cancer. Abbreviations: AJCC = American Joint Committee on Cancer stage system, ASCO = American Society of Clinical Oncology, CCLE = cancer cell line encyclopedia, DFS = disease-free survival, EGFR = epidermal growth factor receptor, ER = estrogen receptors, ERCC1 = excision repair cross complementing 1, FFPE = formalin-fixed paraffin-embedded, GTEx = The Genotypetissue Expression Project, HER-2 = human epidermal growth factor receptor 2, ICGC = International Cancer Genome Consortium, IDC = invasive ductal carcinoma, ISH = in situ hybridization, MBL = multiplex branched DNA liquidchip, NER = nucleotide excision repair, NSCLC = non-small cell lung cancer, OS = overall survival, PR = progesterone receptors, RRM1 = ribonucleotide reductase M1, RT-PCR = reverse transcription-polymerase chain reaction, TCGA = The Cancer Genome Atlas, TNBC = triple-negative breast cancer, TOP2A = topoisomerase IIa, TUBB3 = b-tubulin III, TYMS = thymidylate synthetase.