CCNA2 Is a Prognostic Biomarker for ER+ Breast Cancer and Tamoxifen Resistance

<div><p>Identification of effective prognostic biomarkers and targets are of crucial importance to the management of estrogen receptor positive (ER+) breast cancer. CCNA2 (also known as CyclinA2) belongs to the highly conserved cyclin family and is significantly overexpressed in various cancer types. In this study, we demonstrated that CCNA2 had significant predictive power in distant metastasis free survival, disease free survival, recurrence free survival and overall survival of ER+ breast cancer patients. We also found that CCNA2 was closely associated with tamoxifen resistance. In addition, gene set enrichment analysis (GSEA) revealed that its expression was positively associated with genes overexpressed in endocrine therapy resistant samples. Finally, though CCNA2-Drug interaction network, we demonstrated the interactions between CCNA2 and several available cancer drugs. Overall, we suggest that CCNA2 is a biomarker for the prognosis of ER+ breast cancer and monitoring of tamoxifen efficacy. It's also a promising target for developing new strategies to prevent or even reverse tamoxifen resistance. Moreover, CCNA2 expression may help monitoring tamoxifen efficacy and directing personalized therapies. Nevertheless, in vivo and in vitro experiments and multi-center randomized controlled clinical trials are still needed before its application in clinical settings.</p></div

CCNA2 expression is associated with poor survival and tamoxifen resistance in ER+ breast cancer patients.

<p>Kaplan-Meier plot for DMFS of ER+ (<i>A</i>), ER- (<i>B</i>) or tamoxifen treated (<i>C</i>) breast cancer patients grouped by the tertile of CCNA2 expression levels, significance was assessed by logrank test. (<i>D</i>) Log2 transformed mRNA expression values of CCNA2 in MCF-7 tumor xenografts treated with either tamoxifen or control. P values were calculated by unpaired two-tailed t test. Error bars represent mean ± SEM. (<i>E</i>) mRNA expression values of CCNA2 in tamoxifen resistant/sensitive MCF-7 subclones treated with tamoxifen or control. P values were calculated by unpaired two-tailed t test. Error bars represent mean ± SEM. (<i>F</i>) Gene set enrichment analysis of CCNA2 mRNA expression in relation to tamoxifen resistance gene set using breast cancer expression profiles (N = 2795).</p

Interaction network of CCNA2 and chemotherapeutic drugs.

<p>The gene-drug interaction network shows us how available chemotherapeutic drugs could decrease the expression of CCNA2. For example, Doxorubicin could decrease the expression of CCNA2, while Oxaliplatin could increase the expression of CCNA2.</p

Additional file 1: of A Chinese family affected by lynch syndrome caused by MLH1 mutation

Table S1. 101 gene panel. The gene list of targeted capture panel used in the case. (XLSX 11 kb

Additional file 1: Table S1. of AZGP1 inhibits soft tissue sarcoma cells invasion and migration

Primers sequence. The primer names and sequence for Q-PCR analysis of ZAG and recombinant plasmid construct were listed in the table. (DOC 34 kb

Additional file 3: of A Chinese family affected by lynch syndrome caused by MLH1 mutation

Table S3. Individual sequencing result. All six family members gene test results displayed in individual form. (XLSX 32 kb

MOESM3 of A prospective study on the changes and clinical significance of pre-operative and post-operative circulating tumor cells in resectable gastric cancer

Additional file 3: Figure S1. Correlations of pre-operative CTCs with patient recurrence patterns

MOESM4 of A prospective study on the changes and clinical significance of pre-operative and post-operative circulating tumor cells in resectable gastric cancer

Additional file 4: Figure S2. Patients who have ≥ 4 CTCs/7.5 ml blood pre-operatively had shorter DFS (a, c) and OS (b, d)

MOESM2 of A prospective study on the changes and clinical significance of pre-operative and post-operative circulating tumor cells in resectable gastric cancer

Additional file 2: Table S2. Patient characteristics and CTC numbers in 31 relapsed patients

Multivariate analysis of the prognostic factors in colorectal and esophageal cancer patients by Cox proportional hazard regression model.

<p>Multivariate analysis of the prognostic factors in colorectal and esophageal cancer patients by Cox proportional hazard regression model.</p