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Experimentally derived metastasis gene expression profile predicts recurrence and death in patients with colon cancer.
Sex, Age, Disease stage, Race
View SamplesBackground and Aims: Staging inadequately predicts metastatic risk in colon cancer patients. We used a gene expression profile derived from invasive murine colon cancer cells that were highly metastatic in an immunocompetent mouse model to identify colon cancer patients at risk for recurrence in a phase I, exploratory biomarker study.
Experimentally derived metastasis gene expression profile predicts recurrence and death in patients with colon cancer.
Sex, Age, Disease stage, Race
View SamplesColorectal carcinoma is the third leading cause of cancer-related death in the United States. In order to understand the mechanism/signaling pathways responsible for invasion, migration and metastasis in colorectal cancer, we developed an integrative and comparative genetic approach to infer transcriptional regulatory mechanisms underlying colon cancer progression. Accordingly, we filtered fourteen human colorectal cancer (CRC) microarray data sets, from an immune competent mouse model of metastasis to identify known and novel transcriptional regulators in CRC. Using this approach, Nuclear Factor of Activated T cells (NFAT) family of transcription factors were identified as metastasis driver of colon cancer. NFAT family of transcription factors is known to induce gene transcription in various disease processes, including carcinogenesis. We used parental and metastatic derivatives of MC38 mouse colon cancer cells (MC38Par and MC38Met, respectively) to evaluate the role of NFATc1 in cancer cell invasiveness. We found that high NFATc1 expression correlates with significantly increased (p<0.0001) Trans-Endothelial Invasion (TEI) in MC38Met cells. Conversely, RNAi-based inhibition of NFATc1 expression and functional inhibition with calcineurin inhibitor FK506 in MC38Met cells, both resulted in significant decreased TEI (p=0.0193 & p=0.0003). Furthermore, a set of predicted NFATc1 target mRNAs identified in our original analysis were downregulated by knock-down of NFATc1 or functional inhibition with FK506 in MC38Met cells. The expression level (mRNA) of predicted gene targets were high in human CRC specimens which had higher than median NFATc1 mRNA expression (n=11 out of total 22). The tumor-associated NFATc1 co-regulated gene signature is significantly correlated with both disease-specific and disease-free survival in Stage II and III CRC patients. We have successfully demonstrated a bioinformatics approach to identify a tumor promoter driver gene NFATc1. Our studies suggest a role of NFATc1 towards invasion and its co-regulated gene signature for poor outcomes in colorectal cancer.
Nuclear factor of activated T-cell activity is associated with metastatic capacity in colon cancer.
No sample metadata fields
View SamplesThe purpose of this study was to identify differentially expressed genes in laser-capture microdissected (LCM) invasive mammary carcinomas (IMCs).
Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies.
Specimen part, Disease, Disease stage
View SamplesThe identification of novel tumor-specific markers may improve understanding of melanoma progression and prognostic accuracy. Whole genome expression profiling of 46 primary melanomas, 12 metastases, and 16 normal skin samples using Affymetrix U133 PLUS 2.0 array generated gene lists including both known and new melanoma genes.
Transcriptome profiling identifies HMGA2 as a biomarker of melanoma progression and prognosis.
Sex, Age, Disease
View SamplesThe prognosis of colorectal cancer (CRC) stage II and III patients is still a challenge due to the difficulties of finding robust biomarkers and assays. The majority of published gene signatures of CRC have been generated on frozen colorectal tissues. Because collection of fresh frozen tissues is not routine and the quantity and quality of RNA derived from formalin-fixed paraffin-embedded (FFPE) tissues is vastly inferior to that derived from fresh frozen tissue, a clinical test for improving staging of colon cancer will need to be designed for FFPE tissues in order to be widely applicable. We have designed a custom Nanostring nCounter assay for quantitative assessment of expression of 414 gene elements consisting of multiple published gene signatures for colon cancer prognosis, and systematically compared the gene expression quantification between nCounter data from FFPE and Affymetrix microarray array data from matched frozen tissues using 414 genes.
Comparison of Nanostring nCounter® Data on FFPE Colon Cancer Samples and Affymetrix Microarray Data on Matched Frozen Tissues.
Disease
View SamplesBackground and Aims: Staging inadequately predicts metastatic risk in colon cancer patients. We used a gene expression profile derived from invasive murine colon cancer cells that were highly metastatic in an immunocompetent mouse model to identify colon cancer patients at risk for recurrence in a phase I, exploratory biomarker study.
Experimentally derived metastasis gene expression profile predicts recurrence and death in patients with colon cancer.
Sex, Age, Disease stage, Race
View SamplesPatient selection and specimen collection. Thirty-six freshly frozen tumor samples were prospectively collected from patients undergoing surgery or biopsy for HNSCC at the University of North Carolina (UNC) at Chapel Hill (21 patients) and Vanderbilt University (15 patients). All tissues were snap-frozen in liquid nitrogen within 30 minutes of surgical resection or biopsy, and kept at -80oC until further processing. All patients consented to participation in this study under protocols approved by IRB at the two institutions.
A feed-forward loop involving protein kinase Calpha and microRNAs regulates tumor cell cycle.
No sample metadata fields
View SamplesTo determine how mutation of BRAF affected the response to RAF265, we utilized a tumor orthotopic implant model of early passage melanoma tumors in nude mice from a series of 17 patients with advanced metastatic Tumor growth was compared between RAF265 treatment (40 mg/kg, QD) and diluent control groups. The melanoma associated gene mutation profile and global gene expression profile were determined on these human melanoma samples by SNaPshot and Affymetrix Human Gene ST 1.0 Array, respectively. Tumors were evaluated for growth response to RAF265 in an orthotopic implant model using nude mice. Comparisons were made between gene expression profiles of responders and non-responders, BRAF mutant and BRAF wild type tumors. Analysis of the microarray data revealed responders exhibited enriched expression of genes involved in cell cycle, apoptosis, cell-cell adhesion and initiation of epithelial/mesenchymal transition. It is concluded that RAF265 significantly inhibits the growth of a sub-population of V600E mutant and wild type BRAF human melanoma tumors in vivo and the gene expression profile of this subset of tumors that may predict response to RAF265.
RAF265 inhibits the growth of advanced human melanoma tumors.
Sex, Age, Specimen part
View SamplesIntroduction: Human Papilloma Virus (HPV) is associated with a subset of head and neck squamous cell carcinoma (HNSCC), between 15% and 35% of HNSCC harboring HPV, almost exclusively of subtype 16. Demographic and exposure differences between HPV-positive (+) and negative (-) HNSCCs suggest that HPV(+) tumors may constitute a subclass with different biology, while clinical differences have also been observed. In this study, gene expression profiles of HPV(+) and (-) tumors were compared to further explore the biological effect of HPV in HNSCC. Methods: Thirty-six HNSCC tumors were analyzed for gene expression using Affymetrix Human 133U Plus 2.0 GeneChip and for HPV using consensus primers for HPV L1, E6 and E7 by PCR and RT-PCR. Results: Eight (22%) of 36 tumors were positive for HPV, all of the HPV 16 subtype, and the HPV positive samples also expressed viral HPV E6 mRNA determined by RT-PCR. Patients with HPV(+) HNSCCs were on average younger than those with HPV(-) tumors (mean age 50.2 vs. 58.7). Statistical analysis using Significance Analysis of Microarrays (SAM) based on HPV status as a supervising parameter resulted in a list of 91 genes that were differentially expressed with statistical significance. Results for a sub-set of these genes were verified by RT-PCR. Genes highly expressed in HPV(+) samples included cell cycle regulators (p16INK4A, p18 and CDK2) and transcription factors (TAF7L, RFC4, RPA2 and TFDP2). The microarray data were also investigated using DIGMap to map genes by chromosomal location. A large number of genes on chromosome 3q24-qter was found to be overrepresented in HPV(+) tumors. Conclusion: The gene expression profile associated with HPV reflects alterations in cell cycle and proliferation signals. Further investigation of differentially expressed genes may reveal the unique pathways in HPV(+) tumors that may explain the different natural history and biological properties of these tumors. These properties may be exploited as a target of novel therapeutic agents in HNSCC treatment.
Gene expression differences associated with human papillomavirus status in head and neck squamous cell carcinoma.
No sample metadata fields
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