Article

RACK1: A superior independent predictor for poor clinical outcome in breast cancer

Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China.
International Journal of Cancer (Impact Factor: 5.01). 09/2009; 127(5):1172-9. DOI: 10.1002/ijc.25120
Source: PubMed

ABSTRACT We aimed to investigate the expression of RACK1 in breast cancer, evaluate its role in predicting prognosis and compare with commonly used biomarkers: Ki67, ER, PR and HER-2 for patients with breast cancer. The RACK1 expression and its clinical significance were examined in 160 breast carcinoma patients using immunohistochemistry. Correlations of RACK1 expression with other commonly used biomarkers and survival analyses were assessed. Immunohistochemistry results showed that the number of RACK1 cases scoring 0, 1, and 2 were 66, 54, and 40, respectively. RACK1 staining was strongly related to clinical stage, histological grade, Ki67, ER, PR and HER-2 (all p < 0.05). Consistently, all of the cases exhibiting RACK1 staining score 0 were survivors, whereas the majority (55.0%) of those exhibiting RACK1 staining score 2 were deaths. Kaplan-Meier survival analysis of 160 cases revealed a correlation between higher RACK1 expression levels and shorter overall survival times (p < 0.001). Univariate and multivariate analyses revealed that RACK1, tumor size, lymph node metastasis, and HER-2 were independent prognostic factors (all p < 0.05). Interestingly, receiver operator characteristic (ROC) curves showed that the ROC areas for RACK1, Ki67, ER, PR and HER-2 were 0.833, 0.766, 0.446, 0.387, and 0.689, respectively, and the superiority of RACK1 in sensitivity and specificity as biomarker was demonstrated. To our knowledge, it is the first time to investigate the expression of RACK1, and identified that RACK1 is a superior independent biomarker for diagnosis and prognosis comparing with currently widely used diagnostic index in breast carcinoma.

0 Followers
 · 
121 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: RACK1 is a highly conserved intracellular adaptor protein with significant homology to Gβ and was originally identified as the anchoring protein for activated protein kinase C. In the past 20 years, the number of binding partners and validated cellular functions for RACK1 has increased, which facilitates clarification of its involvement in different biological events. In this review, we will focus on its role in cancer, summarizing its aberrant expression, pro- or anti-oncogenic effects and the underlying mechanisms in various cancers.Oncogene advance online publication, 2 June 2014; doi:10.1038/onc.2014.127.
    Oncogene 06/2014; DOI:10.1038/onc.2014.127 · 8.56 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Breast cancer is one of the most common malignancies worldwide and is the second leading cause of cancer-related mortality among females. miRNAs are a class of small noncoding RNAs that are aberrantly expressed in human cancers. Due to their small size and stability, miRNAs have the potential to be efficacious clinical targets. MicroRNA-320a (miR-320a) has been shown to be dysregulated in multiple malignancies. In the present study, the expression levels of miR-320a were investigated in 15 paraffin-embedded in situ breast carcinoma and 130 invasive breast cancer tissues, and the prognostic value for breast cancer patients was assessed. Chromogenic in situ hybridization revealed that 60/130 (46%) invasive breast cancer tissues exhibited high expression levels of miR-320a (staining index score of ≥4). Furthermore, miR-320a staining was found to significantly correlate with tumor size (P=0.046), clinical stage (P<0.001), lymph node metastasis (P<0.001) and distant metastasis (P=0.006). In addition, patients exhibiting low miR-320a expression levels had shorter overall survival times (P<0.001). Univariate and multivariate analyses revealed that miR-320a was an independent prognostic biomarker for invasive breast cancer (hazard ratio, 0.221; 95% confidence interval, 0.050-0.979; P=0.047). Receiver operator characteristic curves revealed that the prognostic value of miR-320a was enhanced when compared with the widely used prognostic biomarkers (estrogen receptor, progesterone receptor and human epidermal growth factor-2) in invasive breast cancer. The results of the present study suggest that miR-320a presents a potential biomarker for the prognosis of invasive breast cancer, and dysregulation of miR-320a may be involved in invasive breast cancer progression.
    Oncology letters 09/2014; 8(3):1043-1050. DOI:10.3892/ol.2014.2298 · 0.99 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: IntroductionRecurrence or early metastasis remains the predominant cause of mortality in patients with estrogen receptor positive (ER+) mammary carcinoma (MC). However, the molecular mechanisms underlying the initial progression of ER¿+¿MC to metastasis remains poorly understood. Trefoil factor 3 (TFF3) is an estrogen-responsive oncogene in MC. Herein, we provide evidence for a functional role of TFF3 in metastatic progression of ER¿+¿MC.Methods The association of TFF3 expression with clinicopathological parameters and survival outcome in a cohort of MC patients was assessed by immunohistochemistry. The expression of TFF3 in MCF7 and T47D cells was modulated by forced expression or siRNA-mediated depletion of TFF3. mRNA and protein levels were determined using qPCR and western blot. The functional effect of modulation of TFF3 expression in MC cells was determined in vitro and in vivo. Mechanistic analyses were performed using reporter constructs, modulation of signal transducer and activator of transcription 3 (STAT3) expression, and pharmacological inhibitors against c-SRC and STAT3 activity.ResultsTFF3 protein expression was positively associated with larger tumour size, lymph node metastasis, higher stage, and poor survival outcome. Forced expression of TFF3 in ER¿+¿MC cells stimulated colony scattering, cell adhesion to a Collagen I-coated matrix, colony formation on a Collagen I- or Matrigel-coated matrix, endothelial cell adhesion, and transmigration through an endothelial cell barrier. In vivo, forced expression of TFF3 in MCF7 cells stimulated the formation of metastatic nodules in animal lungs. TFF3 regulation of the mRNA levels of epithelial, mesenchymal, and metastatic-related genes in ER¿+¿MC cells were consistent with the altered cell behaviour. Forced expression of TFF3 in ER¿+¿MC cells stimulated phosphorylation of c-SRC that subsequently increased STAT3 activity, which lead to the downregulation of E-cadherin. siRNA-mediated depletion of TFF3 reduced the invasiveness of ER¿+¿MC cells.ConclusionsTFF3 expression predicts metastasis and poor survival outcome of patients with MC and functionally stimulates cellular invasion and metastasis of ER¿+¿MC cells. Adjuvant functional inhibition of TFF3 may therefore be considered to ameliorate outcome of ER¿+¿MC patients.
    Breast cancer research: BCR 09/2014; 16(5):429. DOI:10.1186/s13058-014-0429-3 · 5.88 Impact Factor

Preview

Download
0 Downloads