Metastasis is the predominant cause of death in breast cancer patients. Several lines of evidence have shown that microRNAs (miRs) can have an important role in cancer metastasis. Using isogenic pairs of low and high metastatic lines derived from a human breast cancer line, we have identified miR-149 to be a suppressor of breast cancer cell invasion and metastasis. We also identified GIT1 (G-protein-coupled receptor kinase-interacting protein 1) as a direct target of miR-149. Knockdown of GIT1 reduced migration/invasion and metastasis of highly invasive cells. Re-expression of GIT1 significantly rescued miR-149-mediated inhibition of cell migration/invasion and metastasis. Expression of miR-149 impaired fibronectin-induced focal adhesion formation and reduced phosphorylation of focal adhesion kinase and paxillin, which could be restored by re-expression of GIT1. Inhibition of GIT1 led to enhanced protein degradation of paxillin and α5β1 integrin via proteasome and lysosome pathways, respectively. Moreover, we found that GIT1 depletion in metastatic breast cancer cells greatly reduced α5β1-integrin-mediated cell adhesion to fibronectin and collagen. Low level of miR-149 and high level of GIT1 was significantly associated with advanced stages of breast cancer, as well as with lymph node metastasis. We conclude that miR-149 suppresses breast cancer cell migration/invasion and metastasis by targeting GIT1, suggesting potential applications of the miR-149-GIT1 pathway in clinical diagnosis and therapeutics.

Background:This study was aimed to detect post-chemotherapeutic circulating tumour cells (CTCs) in stage III colon cancer patients and identify those who were at high risk of relapse.Methods:We used human telomerase reverse transcriptase, cytokeratin-19, cytokeratin-20, and carcinoembryonic antigen (CEA) as the biomarkers to detect CTCs in 90 stage III colon cancer patients undergoing curative resection followed by mFOLFOX chemotherapy.Results:Post-chemotherapeutic relapse occurred in 30 (33.3%) patients. By univariate analysis and multivariate proportional hazards regression analysis, perineural invasion (hazard ratio (HR): 2.752; 95% confidence interval (CI): 1.026–7.381), high post-chemotherapeutic serum CEA levels (HR: 2.895; 95% CI: 1.143–7.333) and persistent presence of post-chemotherapeutic CTCs (HR: 6.273; 95% CI: 2.442–16.117) were independent predictors of post-chemotherapeutic relapse. In addition, the persistent presence of post-chemotherapeutic CTCs strongly correlated with reduced disease-free survival and overall survival. Accuracy of detecting relapse in post-chemotherapeutic stage III colon cancer patients by analysing the persistent presence of post-chemotherapeutic CTCs was higher than that by post-chemotherapeutic CEA levels (odds ratio: 50.091 vs 5.211).Conclusion:The persistent presence of post-chemotherapeutic CTCs is a potential powerful surrogate marker for determining clinical outcome in stage III colon cancer patients receiving adjuvant mFOLFOX chemotherapy.

Background:The purpose of this study was to detect postoperative persistent circulating tumour cells (CTCs) in stages II and III colon cancer patients undergoing curative resection and so identify a subgroup of patients who are at high risk for early relapse.Methods:Four mRNA molecular markers including human telomerase reverse transcriptase, cytokeratin-19, cytokeratin-20, and carcinoembryonic antigen (CEA) mRNA were used to detect CTCs in 141 stages II and III colon cancer patients undergoing curative resection to determine the significance of CTCs in postoperative early relapse.Results:Out of 141 patients, postoperative early relapse and non-early relapse/no relapse was found in 48 (34.0%) patients and 93 (66.0%) patients, respectively. Univariately, postoperative early relapse was significantly correlated with lymph node metastasis (P=0.025), vascular invasion (P=0.002), perineural invasion (P=0.001), laparoscopic surgery (P=0.019), high postoperative serum CEA levels (P=0.001), and presence of persistent postoperative CTCs (P<0.001). Using a multivariate proportional hazards regression analysis, the presence of perineural invasion (P=0.034; HR, 1.974; 95% CI: 1.290–3.861), high postoperative serum CEA levels (P=0.020; HR, 2.377; 95% CI: 1.273–4.255), and the presence of persistent postoperative CTCs (P<0.001; HR, 11.035; 95% CI: 4.396–32.190), were demonstrated to be independent predictors for postoperative early relapse. Furthermore, the presence of persistent postoperative CTCs was strongly correlated with a poorer disease-free and overall survival (both P<0.001).Conclusions:This study suggests that molecular detection of persistent postoperative CTCs is a prognostic predictor of early relapse in UICC stage II/III colon cancer patients, and thus could help to define patients with this tumour entity for an enhanced follow-up and therapeutic program.

This study examines whether a higher rate of physician adherence to quality-of-care indicators for colorectal cancer patients is associated with improved survival and using a bubble chart to help interpret physician performance. A set of 13 core measures was used to evaluate the quality of care in 708 colorectal cancer patients treated from 2004 to 2007 at a hospital in Taiwan. A 100% adherence standard was used to measure the relationship of adherence to patient survival. Each indicator assigned by each cancer stage was dichotomously coded. The associations between the adherence and survival rates and demographic characteristics were assessed using Cox's proportional hazard regression. Physician adherence to core indicators was plotted using a bubble chart to motivate physicians' performance adhering to quality-of-care guidelines for colorectal cancer patients. The 100% adherence rate criterion contributed to a relatively low hazard ratio of 0.36 (95% confidence interval, 0.14-0.85; P= 0.02). The association between the adherence rate and survival indicated significant improvements for stage III patients compared with stage I patients. A graphical representation of bubble charts helped to monitor physician performance, which improved the adherence rate to quality-of-care guidelines for colorectal cancer patients.

Background: Hepatocellular carcinoma (HCC) is the most common form of malignant liver tumors, characterized by unfavorable prognosis and low sensitivity to chemotherapy. HCC diagnosis is complicated by late manifestation of symptoms and lack of effective biomarkers. The existing MRI approach does not cover 20% of HCC cases (hypovascular variants). Another problem is differential diagnosis between G1-stage HCC and subclasses of hepatocellular adenoma (HCA). Present study examines the ability of potential biomarkers, previously identified by our group, to differentiate HCC from benign liver tumors represented by HCA and focal nodular hyperplasia (FNH). We also analyzed gene expression changes associated with the development of FNH and HCA in order to identify molecular markers capable of distinguishing between these two neoplasm types. Methods: 61 pairs of surgical biopsies of tumor and non-tumorous liver tissue of patients with HCA (5 cases), FNH (6 cases) and HCC (50 cases) were used in the study. Expression levels of RAB3B, IQGAP3, GPC3, HKDC1, TOP2A, GNAZ, PDGFA and CENPF genes were evaluated using RT-qPCR. Data on gene expression changes were statistically processed and sorted using hierarchical cluster analysis. Results: Significant (p < 0.05) increase in expression level of IQGAP3 (p ¼ 8.8x10 À8), GPC3 (p ¼ 4.2x10 À5), CENPF (p ¼ 5.1x10 À4), and TOP2A (p ¼ 0.042) was detected in HCC tissue but not in benign tumor samples when compared to respective non-tumor samples. HKDC1 and RAB3B overexpression was observed in both HCC and benign tumors. HCA and FNH cases differ considerably by pattern of gene expression changes. HKDC1 expression level is higher in FNH than in HCA (p ¼ 0.017). Conclusions: Overexpression of IQGAP3, GPC3, CENPF and TOP2A genes is specific for HCC, but not HCA and FNH, so these genes are promising candidate biomarkers for differential diagnosis of benign and malignant liver tumors. Activation of RAB3B and HKDC1 genes in FNH and HCA tissue suggests their possible role in the development of these neoplasms. Specific patterns of gene expression changes described for HCA and FNH indicate the difference in molecular mechanisms underlying their pathogenesis and provide a tool for distinguishing these neoplasms from each other.