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ABSTRACT:
PROVIDER: PRJNA853539 | ENA |
REPOSITORIES: ENA
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Project description:Background Breast cancer patients who present in the early stage of disease are affected by metastasis to the axillary group of lymph nodes. The first among this group that is affected is called as sentinel lymph node, and metastasis to this lymph node is crucial for the staging of cancer and the quality of surgical intervention. Sentinel Lymph Node Biopsy (SLNB) that is currently used to assess lymph node metastasis is neither sensitive, nor specific, is time-consuming, thereby necessitating the identification of novel biomarkers that can flag sentinel lymph node metastasis. Methods Breast cancer patients were screened, and those with early stage were recruited in the study. Surgical resection of the breast was followed by identification of sentinel lymph nodes by methylene fluorescent technique. Histo-pathology of fresh frozen section biopsy was used as the gold standard to assign the clinical phenotypes of metastatic (SLNM+) and non-metastatic sentinel lymph nodes (SLNM-). Discovery phase of the experiment included isobaric Tags for Relative and Absolute Quantitation (iTRAQ) technique comprising of six comparative experiments coupled with mass spectrometric analysis on Orbitrap Fusion to identify differentially expressed proteins on Proteome Discoverer 2.4. Functional enrichment and pathway analyses of differentially regulated genes was carried out in DAVID functional annotation tool. Validation was done by ELISA and protein concentrations were used to estimate the ROC for computing diagnostic parameters. Results Based on MS/MS spectra there were 2396 unique protein groups and 81 differentially expressed proteins comparing SLNB + and SLNB -. Nineteen proteins up-regulated, and eight proteins that were down regulated in SLNB+ as compared to SLNB-. Bioinformatic analysis showed the implication of extra cellular matrix proteins and ECM-receptor interaction pathways to be implicated in lymph node metastasis. ELISA confirmed the up-regulation of caveolin 1, collagen α-1, desmin, fibrillin-1, and microfibrillar associated glycoprotein 4 in metastatic, as compared to non-metastatic lymph nodes. These proteins are known to be integral in tumorogenesis, cell proliferation, invasion, cell survival and anti-apoptosis. These proteins have 80%-100%, of sensitivity and specificity to differentiate the two clinical phenotypes. Conclusion Identified extra cellular matrix protein biomarkers have requisite diagnostic parameters to be developed as a translational tool to assess the status of sentinel lymph nodes during mastectomy procedure to guide surgical therapy of axillary lymph nodes in early breast oncology.
2022-05-01 | PXD027668 | Pride
Project description:RATIONALE: Diagnostic procedures, such as lymph node mapping during surgery and sentinel lymph node biopsy, may help doctors find micrometastases and predict cancer recurrence.
PURPOSE: This phase II trial is studying how well lymph node mapping during surgery together with sentinel lymph node analysis and blood testing work in detecting and predicting early micrometastases in patients with colorectal cancer.
| 2051412 | ecrin-mdr-crc
Project description:Cutaneous melanoma first metastasizes into sentinel lymph nodes that control the lymphatic drain from the area of the primary tumor. This observation is used clinically for melanoma patients with primary melanomas thicker than 1mm (tumor stage ≥T2a), for these patients sentinel lymph node biopsy has become an important and routinely performed diagnostic procedure. The importance of sentinel node analysis is reflected by a significant better prognosis of melanoma patients with tumor free sentinel nodes compared to patients with metastatic sentinel nodes. Although intensively studied, not much is known about mechanisms responsible for the development of melanoma metastasis.To analyze gene expression in mouse SLNs of M24met tumor bearing animals as compared to tumor free control animals, SLNs were taken at different time points and analyzed for the presence of human M24met to classify SLNs into control, negative, macro metastatic SLN. After categorized SLNs were subjected to microarray analysis.
2011-07-15 | GSE30688 | GEO
Project description:Background: Cervical lymph node metastasis is a potent prognostic factor in oral squamous cell carcinoma (OSCC). However, lymph nodes resected by sentinel node biopsy or neck dissection are usually diagnosed by examining only one or two sections of the maximal cut surface. Accurate diagnosis of the metastasis in lymph nodes is important but depends on a heavy workload of the pathologist. In this study, we have attempted to identify novel molecular markers to find the harboring cancer cells in the lymph node and establish rapid detection method. Methods: We determined the gene expression profiles of 7 metastatic lymph nodes from patients with OSCC and 1 normal lymph node and 5 salivary glands from non-cancerous patients by microarray analysis. We found the overexpression genes in all metastatic lymph nodes. Subsequently, we examined the expression of these genes in newly 23 metastatic lymph nodes and 9 normal lymph nodes by real-time quantitative RT-PCR (qRT-PCR) assay. Moreover, the rapid detection of lymph node metastasis by these genes was examined using the reverse transcription loop-mediated isothermal amplification (RT-LAMP) method. Result: Among the 4 genes identified by microarray analysis, annexin A8 (ANXA8) and desmoglein 3 (DSG3) were detected in all metastatic lymph nodes at a much higher level but not in normal lymph nodes at all by qRT-PCR. Furthermore, RT-LAMP method targeting ANXA8 rapidly detected almost lymph nodes with metastasis. Conclusions: ANXA8 could be a useful marker for detecting lymph node metastasis in OSCC. Using AB1700 system, we determined the gene expression profiles of lymph nodes with metastasis of OSCC. Normal lymph node and salivary gland tissues were used as control samples.
2015-12-21 | E-GEOD-70604 | biostudies-arrayexpress
Project description: Not available
| S-EPMC8784167 | biostudies-literature
Project description:Background: Validated markers to predict outcome in rectal cancer patients treated with multimodal therapy remain elusive. Identifying molecular profiles for disease prognosis would be required for the design of clinical trials aimed at optimizing risk-adapted therapies. We have therefore used whole genome expression profiling of tumors of a large cohort of patients enrolled in the multicenter trials of the German Rectal Cancer Study Group (GRCSG) to identify molecular profiles for individualized therapy. Methods: We prospectively collected pretherapeutic biopsies from patients (n=300) treated according to the GRCSG trial guidelines from seven different German surgical departments using rigid quality controls. These samples were profiled by global gene expression analysis and a classifier developed to predict postoperative lymph node status and Disease Free Survival (DFS). The performance of the classifier was validated with an independent, prospectively collected set of samples. Findings: The final training and test set included 198 patients. Analyzes for postoperative nodal status and DFS revealed 69 and 674 differentially regulated genes, respectively. Depending on the classifier the accuracy to predict lymph node status ranged from 64% to 69% with negative predictive values between 72% and 74%. Stratification according to DFS resulted in a good (n=99), bad (n=96) and a small very bad prognosis group (n=3). Based on linear discriminant analysis the classifier for positive lymph node status was validated in 47 independent patients and revealed an accuracy of 72% and a positive predictive value of 100%. Thereby, prediction based on molecular profiling is superior to prediction based on conventional clinical markers. Interpretation: Whole genome expression analysis of pretherapeutical biopsies resulted in a molecular classifier of disease prognosis. This classifier was successfully validated. The high positive predictive value for post therapeutic lymph node status allows identification of patients requiring alternative or intensified treatment protocols. These data are currently validated for their clinical applicability and should be taken as basis for future molecular driven clinical trials to develop risk-adapted treatments.
2023-03-31 | GSE40492 | GEO
Project description:Gene expression signatures for B cells from tumor draining lymph node and normal lymph node
| PRJNA320737 | ENA
Project description:Several studies have demonstrated that melanoma-derived exosomes home in sentinel lymph nodes favoring metastasis. Here, we determined the proteomic signature in exosomes derived from lymph node metastatic models. We found a signature of genes over-expressed and proteins hyper-secreted in exosomes related to lymph node metastasis in the B16 mouse melanoma model. Out of these candidates, we found that Emilin1, a protein with an important function in lymph node physiology, was hyper-secreted in exosomes. Interestingly, we found that Emilin1 is degraded and secreted in exosomes as a mechanism favoring metastasis. Indeed, we found that Emilin1 has a tumor suppressor-like role regulating negatively cell viability and migration. Importantly, our in vivo studies demonstrate that Emilin1 overexpression reduced primary tumor growth and metastasis in mouse melanoma models. Analysis in human melanoma samples showed that cells expressing high levels of EMILIN1 are reduced in metastatic lesions. Overall, our analysis suggests a novel mechanism involved in the inactivation of Emilin1 in melanoma favouring melanoma progression and metastasis.
2021-07-16 | PXD018891 | Pride
Project description:Background: Cervical lymph node metastasis is a potent prognostic factor in oral squamous cell carcinoma (OSCC). However, lymph nodes resected by sentinel node biopsy or neck dissection are usually diagnosed by examining only one or two sections of the maximal cut surface. Accurate diagnosis of the metastasis in lymph nodes is important but depends on a heavy workload of the pathologist. In this study, we have attempted to identify novel molecular markers to find the harboring cancer cells in the lymph node and establish rapid detection method. Methods: We determined the gene expression profiles of 7 metastatic lymph nodes from patients with OSCC and 1 normal lymph node and 5 salivary glands from non-cancerous patients by microarray analysis. We found the overexpression genes in all metastatic lymph nodes. Subsequently, we examined the expression of these genes in newly 23 metastatic lymph nodes and 9 normal lymph nodes by real-time quantitative RT-PCR (qRT-PCR) assay. Moreover, the rapid detection of lymph node metastasis by these genes was examined using the reverse transcription loop-mediated isothermal amplification (RT-LAMP) method. Result: Among the 4 genes identified by microarray analysis, annexin A8 (ANXA8) and desmoglein 3 (DSG3) were detected in all metastatic lymph nodes at a much higher level but not in normal lymph nodes at all by qRT-PCR. Furthermore, RT-LAMP method targeting ANXA8 rapidly detected almost lymph nodes with metastasis. Conclusions: ANXA8 could be a useful marker for detecting lymph node metastasis in OSCC.
2015-12-21 | GSE70604 | GEO
Project description:The expression of miRNA in cancer tissues of gastric cancer patients with different lymph node stages was compared. N0 indicated no lymph node metastasis, and N3 indicated 7 or more lymph node metastasis
2021-07-05 | GSE173215 | GEO