MicroRNA epxression patterns can discriminate between patients with oligometastatic and polymetastatic progression: tissues
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Yong Huang
PROVIDER: E-GEOD-25552 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Cancer staging and treatment frequently assume a binary division of tumors into localized or metastatic cancers. We proposed a state of metastatic disease defined by the number of metastases termed oligometastases. Patients with oligometastatic disease may be cured with localized methods of cancer treatment. We analyzed miRNA expression from paraffin blocks of primary or metastatic tumor samples derived from oligometastatic (? 5 metastases) patients treated with high dose localized radiotherapy. We report patterns of miRNA expression in the metastatic and primary tumor samples that identify patients who failed to progress to widespread polymetastases. We created a model of oligometastases of human tumors in immune compromised mice. The miRNA patterns of gene expression derived from patients accurately identified oligometastatic patterns in the mouse model as compared to animals that developed widespread metastases. MiRNA signatures may identify patients most likely to benefit from aggressive curative treatment of limited metastatic disease. Injection of MDA-MB-435-GFP cancer cells into the mammary fat pad of female athymic mice to develop spontaneous macroscopic lung metastasis. Tail vein experimental lung colonization assay was performed to model the development of MDA-MB-435-GFP Oligo- or Poly-metastases in the lung in vivo. Cell lines: Total RNA were derived from MDA-MB-435-L1-GFP (Ol-like) or MDA-MB-435-L1Mic (Poly-like) cell lines.
2010-12-09 | E-GEOD-25967 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE25552: microRNA epxression patterns can discriminate between patients with oligometastatic and polymetastatic progression: tissues GSE25967: microRNA epxression patterns can discriminate between patients with oligometastatic and polymetastatic progression: cell lines Refer to individual Series
2010-12-09 | E-GEOD-25968 | biostudies-arrayexpress
Project description:We previously proposed a clinically meaningful intermediate metastatic state defined by a limited number of new metastases (≤5) after 3 months of follow-up, termed oligometastasis that has the curative potential by local cancer treatments as in contrast to the incurable widespread polymetastatic dissemination. While animal models of polymetastasis exist and this phenotype can be further enhanced upon serial in vivo passage, animal models of oligometastasis are not available. Here, we report the creation of an oligometastasis model of MDA-MB-435 human tumor in nude mice in which the oligometastatic phenotype exhibits stability during successive in vivo testing, and satisfies the criteria of ≤ 5 total body macroscopic metastases definition of the human cancer oligometastatic state. In parallel, we also developed an MDA-MB-435 polymetastatic model in which the polymetastatic dissemination pattern was either poly-foci at lung, or involved multiple anatomic sites including lung, heart, muscle, ovaries, kidney, brain and pleura. We have conducted microRNA expression profiling of cell lines derived from distinct lungs of oligo- and poly-metastatic animals. Animal model-derived microRNA expression features that discriminate oligometastatic cell lines from those of polymetastases accurately identify oligometastatic patients who failed to develop widespread metastases (P=0.005). These results demonstrate the clinical relevance of the oligo- and polymetastatic animal models we have developed and their potential in elucidating the molecular underpinnings of oligometastasis progression. We developed a stable human tumor (MDA-MB-435-GFP) xenograft model of oligometastatic and polymetastatic progression by conducting three consecutive rounds of experimental lung colonization assays. In the first round, we generated oligometastases-like lung derivative MDA-MB-435-L1-GFP (L1) or polymetastases-like MDA-MB-435-L1Mic-GFP (L1Mic) cell lines. We subsequently generated three oligometastatic L1 lung cell lines as well as four polymetastatic L1Mic lung cell lines from seven distinct animals of the second in vivo passage for further biological characterization and for microRNA expression analysis.
2011-05-21 | E-GEOD-29430 | biostudies-arrayexpress
Project description:Cancer staging and treatment frequently assume a binary division of tumors into localized or metastatic cancers. We proposed a state of metastatic disease defined by the number of metastases termed oligometastases. Patients with oligometastatic disease may be cured with localized methods of cancer treatment. We analyzed miRNA expression from paraffin blocks of primary or metastatic tumor samples derived from oligometastatic (? 5 metastases) patients treated with high dose localized radiotherapy. We report patterns of miRNA expression in the metastatic and primary tumor samples that identify patients who failed to progress to widespread polymetastases. We created a model of oligometastases of human tumors in immune compromised mice. The miRNA patterns of gene expression derived from patients accurately identified oligometastatic patterns in the mouse model as compared to animals that developed widespread metastases. MiRNA signatures may identify patients most likely to benefit from aggressive curative treatment of limited metastatic disease. Injection of MDA-MB-435-GFP cancer cells into the mammary fat pad of female athymic mice to develop spontaneous macroscopic lung metastasis. Tail vein experimental lung colonization assay was performed to model the development of MDA-MB-435-GFP Oligo- or Poly-metastases in the lung in vivo.
2010-12-09 | GSE25967 | GEO
Project description:Background: Many strategies to define subtypes and treat cancer relies on a presumption of either localized or widespread (poly)metastatic disease. We proposed an intermediate state of metastasis termed oligometastasis(es) characterized by limited metastatic progression and amenable to treatment by localized methods e.g. surgery or radiotherapy. Methods: To understand the biological basis of oligometastatic and polymetastatic progression, we analyzed microRNA expression patterns from lung tumor samples of patients with less than five metastases at first metastasis presentation and treated with metastasis-directed surgery. Results: Patients were stratified into four subgroups of oligo- and poly-metastatic progression based on the rate of metastatic progression over follow-up period. We prioritized microRNAs between the extremes of oligo- vs. poly-metastatic progression and validated their capacity to distinguish these phenotypes and predict survival in an independent validation dataset. Conclusions: Our results provide further evidence for the biological underpinnings of oligometastasis(es) and potential microRNA candidates to predict progression trajectories of patients and optimize corresponding metastasis-directed treatment. We collected tumor samples from 63 patients that (i) had between one and five metastasis(es) at first metastatic presentation and no clinical or radiologic evidence of metastases in the pleural, peritoneal, pericardial or retroperitoneal cavities,(ii) at the time of lung surgery, had every site of known metastases treated with definitive intent, and (iii) had a minimum of 16 months of follow-up after surgery was required. Total RNA were derived from FFPE metastatic tissue samples. Patient samples were subsequently classified into 3 groups: those from patients with high, intermediate and low rates of progression.
2012-06-13 | E-GEOD-38698 | biostudies-arrayexpress
Project description:Angiogenesis and lymphangiogenesis have important roles in cancer progression and chronic inflammatory diseases, but efficient therapies against these diseases have been hampered by the lack of identified vascular lineage-specific markers and growth factors. Using transcriptional profiling of matched pairs of human dermal blood vascular and lymphatic endothelial cells, we first identified 236 lymphatic and 342 blood vascular signature genes. In silico analyses of the biologic pathways associated with these genes revealed lineage-specific functions for each cell type. Using a selection of 85 identified vascular lineage-specific genes, we developed a TaqMan RT-PCR-based, microfluidic card-formatted low-density microvascular differentiation array (LD-MDA) that was used to reliably identify and quantify the degree of lineage-specific differentiation in different types of endothelial cells, and to detect admixture of lymphatic endothelial cells in commercial preparations of microvascular endothelial cells. Application of Prediction Relevance Ranking and analysis of variance of LD-MDA expression profiles of 43 lesional skin samples obtained from patients with the chronic inflammatory disease psoriasis led to identification of cytokines which are significantly associated with angiogenesis or lymphangiogenesis in vivo. In particular, interleukin-7 and fibroblast growth factor-12 were identified as novel (lymph)angiogenic factors. This technology provides a novel tool to quantify lineage-specific vascular differentiation and to characterize (lymph)angiogenesis in clinical samples obtained from angiogenic diseases. Keywords: Quantitative real time RT-PCR, cell type comparison Guided by the gene array results, we selected 54 LEC-specific genes and 31 BEC-specific genes, based upon their consistent and strong specific expression in LEC or BEC, as well as on their assignment to important biological pathways. In addition, the five pan-endothelial cell marker genes PECAM-1, vWF, KDR, TEK, CDH5 and the six endogenous control genes ACTB, GAPDH, PGK1, PPIA, RPLP0 and S18 were included in the design of the LD-MDA. The LD-MDA was then used to evaluate the lineage-specific differentiation of a total of 10 independent lines of primary human dermal LEC, of 8 independent lines of primary human dermal BEC, of two independent lines of HUVEC cells, of the immortalized human microvascular endothelial cell line HMEC-1, of the immortalized human epidermal keratinocyte line HaCaT, and of primary human dermal fibroblasts. After extraction of total RNA, the mRNA expression levels of the 96 genes were analyzed by quantitative RT-PCR using the 7900HT Real-Time PCR System (Applied Biosystems).
2008-10-04 | E-GEOD-11306 | biostudies-arrayexpress
Project description:Angiogenesis and lymphangiogenesis have important roles in cancer progression and chronic inflammatory diseases, but efficient therapies against these diseases have been hampered by the lack of identified vascular lineage-specific markers and growth factors. Using transcriptional profiling of matched pairs of human dermal blood vascular and lymphatic endothelial cells, we first identified 236 lymphatic and 342 blood vascular signature genes. In silico analyses of the biologic pathways associated with these genes revealed lineage-specific functions for each cell type. Using a selection of 85 identified vascular lineage-specific genes, we developed a TaqMan RT-PCR-based, microfluidic card-formatted low-density microvascular differentiation array (LD-MDA) that was used to reliably identify and quantify the degree of lineage-specific differentiation in different types of endothelial cells, and to detect admixture of lymphatic endothelial cells in commercial preparations of microvascular endothelial cells. Application of Prediction Relevance Ranking and analysis of variance of LD-MDA expression profiles of 43 lesional skin samples obtained from patients with the chronic inflammatory disease psoriasis led to identification of cytokines which are significantly associated with angiogenesis or lymphangiogenesis in vivo. In particular, interleukin-7 and fibroblast growth factor-12 were identified as novel (lymph)angiogenic factors. This technology provides a novel tool to quantify lineage-specific vascular differentiation and to characterize (lymph)angiogenesis in clinical samples obtained from angiogenic diseases. Keywords: Quantitative real time RT-PCR, psoriasis (chronic inflammation) study Guided by the gene array results, we selected 54 LEC-specific genes and 31 BEC-specific genes, based upon their consistent and strong specific expression in LEC or BEC, as well as on their assignment to important biological pathways. In addition, the five pan-endothelial cell marker genes PECAM-1, vWF, KDR, TEK, CDH5 and the six endogenous control genes ACTB, GAPDH, PGK1, PPIA, RPLP0 and S18 were included in the design of the LD-MDA. After extraction of total RNA, the mRNA expression levels of the 96 genes were analyzed by quantitative RT-PCR using the 7900HT Real-Time PCR System (Applied Biosystems).
2008-10-04 | E-GEOD-11307 | biostudies-arrayexpress
Project description:Angiogenesis and lymphangiogenesis have important roles in cancer progression and chronic inflammatory diseases, but efficient therapies against these diseases have been hampered by the lack of identified vascular lineage-specific markers and growth factors. Using transcriptional profiling of matched pairs of human dermal blood vascular and lymphatic endothelial cells, we first identified 236 lymphatic and 342 blood vascular signature genes. In silico analyses of the biologic pathways associated with these genes revealed lineage-specific functions for each cell type. Using a selection of 85 identified vascular lineage-specific genes, we developed a TaqMan RT-PCR-based, microfluidic card-formatted low-density microvascular differentiation array (LD-MDA) that was used to reliably identify and quantify the degree of lineage-specific differentiation in different types of endothelial cells, and to detect admixture of lymphatic endothelial cells in commercial preparations of microvascular endothelial cells. Application of Prediction Relevance Ranking and analysis of variance of LD-MDA expression profiles of 43 lesional skin samples obtained from patients with the chronic inflammatory disease psoriasis led to identification of cytokines which are significantly associated with angiogenesis or lymphangiogenesis in vivo. In particular, interleukin-7 and fibroblast growth factor-12 were identified as novel (lymph)angiogenic factors. This technology provides a novel tool to quantify lineage-specific vascular differentiation and to characterize (lymph)angiogenesis in clinical samples obtained from angiogenic diseases. This SuperSeries is composed of the following subset Series: GSE11306: Quantification of vascular lineage-specific differentiation (cell type comparison) GSE11307: Quantification of vascular lineage-specific differentiation, psoriasis (chronic inflammation) study Keywords: SuperSeries Refer to individual Series
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2014-01-30 | E-GEOD-54492 | biostudies-arrayexpress