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1.  TWIST1 Is Expressed in Colorectal Carcinomas and Predicts Patient Survival 
PLoS ONE  2011;6(3):e18023.
TWIST1 is a transcription factor that belongs to the family of basic helix-loop-helix proteins involved in epithelial-to-mesenchymal transition and invasion processes. The TWIST1 protein possesses oncogenic, drug-resistant, angiogenic and invasive properties, and has been related with several human tumors and other pathologies. Colorectal cancer is one of the tumors in which TWIST1 is over-expressed, but its involvement in the clinical outcome of the disease is still unclear. We tested, by RT-PCR, the expression levels of TWIST1 in normal and tumor paired-sample tissues from a series of 151 colorectal cancer patients, in order to investigate its prognostic value as a tumor marker. TWIST1 expression was restricted to tumor tissues (86.1%) and correlated with lymph node metastasis (LNM). Adjusted analysis showed that the expression levels of TWIST1 correlated with overall survival (OS) and disease-free survival (DFS). Importantly, TWIST1 expression levels predicted OS specifically at stages I and II. Moreover, patients with stage II tumors and high TWIST1 levels showed even shorter survival than patients with stage III tumors. These results suggest that TWIST1 expression levels could be a tumor indicator in stage II patients and help select patients at greater risk of poor prognosis who might benefit from adjuvant chemotherapy.
doi:10.1371/journal.pone.0018023
PMCID: PMC3065458  PMID: 21464926
2.  Profiling Essential Genes in Human Mammary Cells by Multiplex RNAi Screening 
Science (New York, N.Y.)  2008;319(5863):617-620.
By virtue of their accumulated genetic alterations, tumor cells may acquire vulnerabilities that create opportunities for therapeutic intervention. We have devised a massively parallel strategy for screening short hairpin RNA (shRNA) collections for stable loss-of-function phenotypes. We assayed from 6000 to 20,000 shRNAs simultaneously to identify genes important for the proliferation and survival of five cell lines derived from human mammary tissue. Lethal shRNAs common to these cell lines targeted many known cell-cycle regulatory networks. Cell line–specific sensitivities to suppression of protein complexes and biological pathways also emerged, and these could be validated by RNA interference (RNAi) and pharmacologically. These studies establish a practical platform for genome-scale screening of complex phenotypes in mammalian cells and demonstrate that RNAi can be used to expose genotype-specific sensitivities.
doi:10.1126/science.1149185
PMCID: PMC2981861  PMID: 18239125
3.  Extracellular Tumor-Related mRNA in Plasma of Lymphoma Patients and Survival Implications 
PLoS ONE  2009;4(12):e8173.
Background
We studied anomalous extracellular mRNAs in plasma from patients with diffuse large B-cell lymphoma (DLBCL) and their survival implications. mRNAs studied have been reported in the literature as markers of poor (BCL2, CCND2, MYC) and favorable outcome (LMO2, BCL6, FN1) in tumors. These markers were also analyzed in lymphoma tissues to test possible associations with their presence in plasma.
Methodology/Principal Findings
mRNA from 42 plasma samples and 12 tumors from patients with DLBCL was analyzed by real-time PCR. Samples post-treatment were studied. The immunohistochemistry of BCL2 and BCL6 was defined. Presence of circulating tumor cells was determined by analyzing the clonality of the immunoglobulin heavy-chain genes by PCR. In DLBCL, MYC mRNA was associated with short overall survival. mRNA targets with unfavorable outcome in tumors were associated with characteristics indicative of poor prognosis, with partial treatment response and with short progression-free survival in patients with complete response. In patients with low IPI score, unfavorable mRNA targets were related to shorter overall survival, partial response, high LDH levels and death. mRNA disappeared in post-treatment samples of patients with complete response, and persisted in those with partial response or death. No associations were found between circulating tumor cells and plasma mRNA. Absence of BCL6 protein in tumors was associated with presence of unfavorable plasma mRNA.
Conclusions/Significance
Through a non-invasive procedure, tumor-derived mRNAs can be obtained in plasma. mRNA detected in plasma did not proceed from circulating tumor cells. In our study, unfavorable targets in plasma were associated with poor prognosis in B-cell lymphomas, mainly MYC mRNA. Moreover, the unfavorable targets in plasma could help us to classify patients with poor outcome within the good prognosis group according to IPI.
doi:10.1371/journal.pone.0008173
PMCID: PMC2788245  PMID: 20016842
4.  Cyfip1 is a putative invasion suppressor in epithelial cancers 
Cell  2009;137(6):1047-1061.
Summary
Identification of bona fide tumor suppressors is often challenging because of the large number of alterations present in most human cancers. To evaluate candidates present within regions recurrently deleted in human cancers we coupled high-resolution genomic analysis with a two-stage genetic study using RNA interference (RNAi). We found that Cyfip1, a subunit of the WAVE complex, which regulates cytoskeletal dynamics, is commonly deleted in human epithelial cancers. Reduced expression of Cyfip1 is commonly observed during invasion of epithelial tumors and it associated with poor prognosis in same tumor types. Silencing of Cyfip1 disturbed normal epithelial morphogenesis in vitro and cooperated with oncogenic Ras to produce invasive carcinomas in vivo. Mechanistically, we have linked alterations in WAVE-regulated actin dynamics with impaired cell-cell adhesion and cell-ECM interactions. Thus, we propose Cyfip1 as an invasion suppressor gene.
doi:10.1016/j.cell.2009.04.013
PMCID: PMC2754270  PMID: 19524508
5.  Circulating Bmi-1 mRNA as a possible prognostic factor for advanced breast cancer patients 
Introduction
Deregulation of Polycomb member Bmi-1 is involved in cell proliferation and human oncogenesis. Modulation of Bmi-1 is found in several tumor tissues, including primary breast carcinomas; however, analysis of Bmi-1 in plasma of cancer patients has not been reported. This is the first study that evaluates Bmi-1 in plasma by using a large series of primary breast carcinomas to investigate the presence at diagnosis of detectable Bmi-1 mRNA in plasma and possible correlations between this event and a series of clinical-pathological parameters of the tumors.
Methods
Bmi-1 expression levels were quantified in plasma of 111 breast cancer patients and in 20 healthy controls by real-time quantitative polymerase chain reaction.
Results
Cancer patients with the presence of Bmi-1 mRNA in plasma had higher levels of Bmi-1 expression than healthy controls with Bmi-1 mRNA in plasma. The higher expression levels of Bmi-1 correlated with well-established markers of poor clinical outcome in breast cancer such as positive p53 immunostaining and negative progesterone receptors. Moreover, we described for the first time a statistically significant correlation between Bmi-1 expression in plasma of breast cancer patients and disease-free and overall survival in advanced stages.
Conclusion
Our results suggest that levels of Bmi-1 expression may be a surrogate marker of poor prognosis and may become clinically useful as noninvasive diagnostic markers.
doi:10.1186/bcr1760
PMCID: PMC2206731  PMID: 17711569

Results 1-5 (5)