Extensive analysis of the molecular biomarkers excision repair cross complementing 1, ribonucleotide reductase M1, β-tubulin III, thymidylate synthetase, and topoisomerase IIα in breast cancer

Abstract

Excision repair cross complementing 1 ( ERCC1 ), ribonucleotide reductase M1 ( RRM1 ), β-tubulin III ( TUBB3 ), thymidylate synthetase ( TYMS ), and topoisomerase IIα ( 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 TOP2A were significantly associated with the characteristics of menopausal status, tumor size, lymph node metastasis, 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 and RRM1 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.

Predictive and Prognostic Significance of mRNA Expression and DNA Copies Aberrations of ERCC1, RRM1, TOP1, TOP2A, TUBB3, TYMS, and GSTP1 Genes in Patients with Breast Cancer

“…In a recent work, it was shown that the expression levels of ERCC1 , TYMS, and TOP2α were significantly associated with clinical and pathological parameters: menopausal status, tumor size, lymph node metastasis, hormone receptor status, triple-negative status, Ki-67 index, and epidermal growth factor receptor [ 31 ]. With respect to ERCC1 gene, the higher intensity was significantly related to T 1 tumor (mean rank: 64.79 > 42.26, p < 0.001), ER-positive (mean rank: 54.98 > 37.41, p = 0.002), PR-positive (mean rank: 58.35 > 39.05, p < 0.001) and Ki-67 < 20% (mean rank: 66.00 > 44.30, p = 0.001).…”