MicroRNA expression profiling of paired primary and lymph node metastatic breast cancer patients
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE148846 | GEO | 2020/05/31
REPOSITORIES: GEO
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Project description:The microenvironment of lymph node metastasized tumors (LNMT) determines tumor progression and response to therapy, but a systematic study of LNMT is lacking. Here, we generate single-cell maps of primary tumors (PTs) and paired LNMTs in 8 breast cancer patients. We demonstrate that the activation, cytotoxicity, and proliferation of T cells are suppressed in LNMT compared with PT. CD4+CXCL13+ T cells in LNMT are more likely to differentiate into an exhausted state. Interestingly, LAMP3+ dendritic cells in LNMT display lower T cell priming and activating ability than in PT. Additionally, we identify a subtype of PLA2G2A+ cancer-associated fibroblasts enriched in HER2+ breast cancer patients that promotes immune infiltration. We also show that the antigen-presentation pathway is downregulated in malignant cells of the metastatic lymph node. Altogether, we characterize the microenvironment of LNMT and PT, which may shed light on the individualized therapeutic strategies for breast cancer patients with lymph node metastasis.
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Project description:Breast cancer (BC) is the foremost cause of cancer-related deaths in women. BC patients are oftentimes presented with lymph node metastasis (LNM), which increases their risk of recurrence. Compelling data have recently implicated microRNAs in promoting BC metastasis. Therefore, the identification of microRNA (miRNA)-based molecular signature associated with LNM could provide an opportunity for a more personalized treatment for BC patients with high risk of LNM. In current study, we performed comprehensive miRNA profiling in matched primary breast and LNM and identified 40 miRNAs, which were differentially expressed in LNM compared to primary tumors. The expression of 14 miRNAs (Up: hsa-miR-155-5p, hsa-miR-150-5p, hsa-miR-146a-5p, hsa-miR-142-5p and down: hsa-miR-200a-3p, hsa-miR-200b-3p, hsa-miR-200c-3p, hsa-miR-205-5p, hsa-miR-210-3p, hsa-miR-214-3p, hsa-miR-141-3p, hsa-miR-127-3p, hsa-miR-125a-5p, and hsa-let-7c-5p) was subsequently validated in a second cohort of 32 breast and 32 matched LNM tumor tissues. Mechanistically, forced expression of hsa-miR-205-5p, or hsa-miR-214-3p epigenetically inhibited MDA-MB-231 cell proliferation, colony formation, and cell migration. Global gene expression profiling on MDA-MB-231 cells overexpressing hsa-miR-205-5p, or hsa-miR-214-3p in combination with in silico target prediction and ingenuity pathway analyses identified multiple bona fide targets for hsa-miR-205-5p, hsa-miR-214-3p affecting cellular proliferation and migration. Interestingly, interrogation of the expression levels of hsa-miR-205 and hsa-miR-214 in the METABRIC breast cancer dataset revealed significantly poor overall survival in patients with downregulated expression of miR-205 [HR = 0.75 (0.61-0.91)], p = 0.003 and hsa-miR-214 [HR = 0.74 (0.59-0.93) p = 0.008]. Our data unraveled the miRNA-transcriptional landscape associated with LNM and provide novel insight on the role of several miRNAs in promoting BC LNM, and suggest their potential utilization in the clinical management of BC patients.
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Project description:This study aimed to investigate the microRNA expression profile of mechnically strained human periodontal ligament-derived stem cells, and SurePrint G3 Human v16 miRNA Array (Agilent) was employed as a screening platform. We discovered 39 differentially expressed microRNAs between the stretched and the static control group. Human periodontal ligament-derived stem cells were cultured on elastic silicone membranes and either subjected to a dynamic mechanical strain protocol (2hr, 5% elongation, 0.5Hz) or left undisturbed. Total RNA was collected and extracted by TRIzol. RNA samples with 28S/18S ratios in the range of 1.4 to 1.8 were used for microRNA microarray analysis using the Agilent SurePrint G3 Human v16 miRNA Array Kit. The samples in each group were triplicated.
2014-09-28 | E-GEOD-41337 | biostudies-arrayexpress
Project description:IntroductionThe incidence of malignant melanoma has increased over the past 25 years in the UK, but death rates have remained fairly constant. The 5-year survival rate ranges from 20% to 95%, depending on disease stage. Risks are greater in white populations and in people with higher numbers of skin naevi.Methods and outcomesWe conducted a systematic overview, aiming to answer the following clinical question: What is the evidence for performing a sentinel lymph node biopsy in people with malignant melanoma with clinically uninvolved lymph nodes? We searched: Medline, Embase, The Cochrane Library and other important databases up to October 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview).ResultsAt this update, searching of electronic databases retrieved 221 studies. After deduplication and removal of conference abstracts, 99 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 58 studies and the further review of 41 full publications. Of the 41 full articles evaluated, one systematic review and three RCTs were added at this update. We performed a GRADE evaluation for two PICO combinations.ConclusionsIn this systematic overview, we evaluated the evidence for performing sentinel lymph node biopsy in people with malignant melanoma with clinically uninvolved lymph nodes.
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Project description:This study aimed to investigate the microRNA expression profile of mechnically strained human periodontal ligament-derived stem cells, and SurePrint G3 Human v16 miRNA Array (Agilent) was employed as a screening platform. We discovered 39 differentially expressed microRNAs between the stretched and the static control group.
2014-09-28 | GSE41337 | GEO
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Project description:Schwannomas commonly arise in the torso, extremities, and mediastinum. However, no interlobar lymph node (#11i) lesions have ever been reported. This is a thought-provoking case, because it involved a schwannoma arising in a lymph node mimicking metastatic pulmonary carcinoma. A 72-year-old man was diagnosed with primary pulmonary carcinoma, and 18F-fluorodeoxyglucose (FDG) positron emission tomography demonstrated high FDG uptake in the primary lesion and in #11i, which suggested metastasis (clinical stage IIA). A right lower lobectomy with lymph node dissection was performed. Fortunately, the enlarged #11i was a schwannoma and not metastasis. The take-home message is "a patient with multiple neuromatosis tends to have schwannomas throughout the body".
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Project description:The microenvironment of lymph node metastasized tumors (LNMT) determines tumor progression and response to therapy, but a systematic study of LNMT is lacking. Here, we generate single-cell maps of primary tumors (PTs) and paired LNMTs in 8 breast cancer patients. We demonstrate that the activation, cytotoxicity, and proliferation of T cells are suppressed in LNMT compared with PT. CD4+CXCL13+ T cells in LNMT are more likely to differentiate into an exhausted state. Interestingly, LAMP3+ dendritic cells in LNMT display lower T cell priming and activating ability than in PT. Additionally, we identify a subtype of PLA2G2A+ cancer-associated fibroblasts enriched in HER2+ breast cancer patients that promotes immune infiltration. We also show that the antigen-presentation pathway is downregulated in malignant cells of the metastatic lymph node. Altogether, we characterize the microenvironment of LNMT and PT, which may shed light on the individualized therapeutic strategies for breast cancer patients with lymph node metastasis.
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Project description:4 pairs of matched primary versus metastatic tumor tissues from formalin-fixed, paraffin-embedded (FFPE) tissue bank,and two frozen lung tumor tissues from patients with primary orlymph metastasis. Then performed tandem mass tag (TMT) labeling and quantitative mass spectrometry analysis. A549 Cells we used was overexpressed luceiferase and designated as L0,underwent 3rounds selection in vivo to form L2, L6 that were metastatic to the spinal. We cultured L0 cells in "light" medium, L2,L6 in "medium heavy" and "heavy" respectively. Harvesting of cells and combined in 1:1:1 ratio, peptides were seperated using high-PH RPLC and analyzed by LC-MS/MS.
2022-02-17 | PXD025052 | Pride
Project description:Rationale: Sentinel lymph node biopsy (SLNB) is a well-established minimally invasive staging procedure that maps the spread of tumour metastases from their primary site to the regional lymphatics. Currently, the procedure requires the local peri-tumoural injection of radiolabelled and/or optical agents, and is therefore operator dependent, disruptive to surgical workflow and restricted largely to a small subset of malignancies that can be readily accessed externally for local tracer injection. The present study set out to determine whether intravenous (IV) infusion of a tumor-targeted tracer could identify sentinel and metastatic lymph nodes (LNs) in order to overcome these limitations. Methods: We examined 27 patients with oral squamous cell carcinoma (OSCC), 18 of whom were clinically node negative (cN0). Patients were infused intravenously with 50mg of Panitumumab-IRDye800CW prior to surgical resection of their primary tumour with neck dissection and/or SLNB. Lymphadenectomy specimens underwent fluorescence molecular imaging to evaluate tracer distribution to LNs. Results: A total of 960 LNs were analysed, of which 34 (3.5%) contained metastatic disease. Panitumumab-IRDye800CW preferentially localized to metastatic and sentinel LNs as evidenced by a higher fluorescent signal relative to other lymph nodes. The median MFI of metastatic LNs was significantly higher than the median MFI of benign LNs (0.06 versus 0.02, p < 0.05). Furthermore, selecting the highest five fluorescence intensity LNs from individual specimens resulted in 100% sensitivity, 85.8% specificity and 100% negative predictive value (NPV) for the detection of occult metastases and 100% accuracy for clinically staging the neck. In the cN+ cohort, assessment of the highest 5 fluorescence LNs per patient had 87.5% sensitivity, 93.2% specificity and 99.1% NPV for the detection of metastatic nodes. Conclusion: When intravenously infused, a tumour-targeted tracer localized to sentinel and metastatic lymph nodes. Further validation of an IV tumor-targeted tracer delivery approach for SLNB could dramatically change the practice of SLNB, allowing its application to other malignancies where the primary tumour is not accessible for local tracer injection.
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