Single-cell RNA sequencing reveals the mechanism of human breast cancer metastasis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE158399 | GEO | 2021/08/08
REPOSITORIES: GEO
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Project description:To obtain more information about the lymph node metastasis of breast cancer cells, we selected the matched positive lymph nodes (PL), and negative lymph nodes (NL) of the same patient to perform integrated analysis. The PL, NL samples were analysed with single-cell ATAC sequencing.
2021-08-08 | GSE158398 | GEO
Project description:To obtain more information about the lymph node metastasis of breast cancer cells, we selected the matched primary breast cancer (PC) and 2 lymph nodes (LN) of 5 patients to perform integrated analysis. The PC, LN samples were analysed with single-cell RNA sequencing.
2021-10-13 | GSE180286 | GEO
Project description:To obtain more information about the lymph node metastasis of breast cancer cells, we selected the positive lymph nodes (PL) of the two patients to perform integrated analysis. The two PL samples were analysed with single-cell RNA sequencing.
2023-03-02 | GSE188807 | GEO
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:The Affymetrix SNP/CNV (SNP 6.0) platform was used to analyze a cell line model of lymph node metastasis comprised of a poorly metastatic MDA-MB-468GFP human breast adenocarcinoma cell line and its highly metastatic variant (468LN). DNA derived from 2 biological replicates of a highly metastatic (via lymph nodes) breast cancer cell line (468GFP-LN) was compared to 2 biological replicates of DNA prepared from the parental cell line, 468GFP.
2010-05-20 | E-GEOD-14867 | biostudies-arrayexpress
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: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:Lymph node involvement is a major prognostic variable in breast cancer. Whether the molecular mechanisms that drive breast cancer cells to colonize lymph nodes are shared with their capacity to form distant metastases is yet to be established. In a transcriptomic survey aimed at identifying molecular factors associated with lymph node involvement of ductal breast cancer, we found that luminal differentiation, assessed by the expression of estrogen receptor (ER) and/or progesterone receptor (PR) and GATA3, was only infrequently lost in node-positive primary tumors and in matched lymph node metastases. The transcription factor GATA3 critically determines luminal lineage specification of mammary epithelium and is widely considered a tumor and metastasis suppressor in breast cancer. Strong expression of GATA3 and ER in a majority of primary node-positive ductal breast cancer was corroborated by quantitative RT-PCR and immunohistochemistry in the initial sample set, and by immunohistochemistry in an additional set from 167 patients diagnosed of node-negative and positive primary infiltrating ductal breast cancer, including 102 samples from loco-regional lymph node metastases matched to their primary tumors, as well as 37 distant metastases. These observations suggest that loss of luminal differentiation is not a major factor driving the ability of breast cancer cells to colonize regional lymph nodes. The transcriptomic study comprises 16 samples from Lymph node metastasis from infiltrating ductal breast carcinoma, 18 samples from Primary node-positive infiltrating ductal,7 samples from Primary node-negative infiltrating ductal and 3 samples from Unaffected lymph node were included. Their RNA was isolated and prepared for hybridization to human Affymetrix GeneChip arrays.
2013-03-05 | E-GEOD-44408 | biostudies-arrayexpress
Project description: Lymph node involvement is a major prognostic variable in breast cancer. Whether the molecular mechanisms that drive breast cancer cells to colonize lymph nodes are shared with their capacity to form distant metastases is yet to be established. In a transcriptomic survey aimed at identifying molecular factors associated with lymph node involvement of ductal breast cancer, we found that luminal differentiation, assessed by the expression of estrogen receptor (ER) and/or progesterone receptor (PR) and GATA3, was only infrequently lost in node-positive primary tumors and in matched lymph node metastases. The transcription factor GATA3 critically determines luminal lineage specification of mammary epithelium and is widely considered a tumor and metastasis suppressor in breast cancer. Strong expression of GATA3 and ER in a majority of primary node-positive ductal breast cancer was corroborated by quantitative RT-PCR and immunohistochemistry in the initial sample set, and by immunohistochemistry in an additional set from 167 patients diagnosed of node-negative and –positive primary infiltrating ductal breast cancer, including 102 samples from loco-regional lymph node metastases matched to their primary tumors, as well as 37 distant metastases. These observations suggest that loss of luminal differentiation is not a major factor driving the ability of breast cancer cells to colonize regional lymph nodes.
2013-03-05 | GSE44408 | GEO
Project description:Metastasis is responsible for the majority of deaths in a variety of cancer types, including breast cancer. Although several factors or biomarkers have been identified to predict the outcome of patients with breast cancer, few studies have been conducted to identify metastasis-associated biomarkers. Quantitative iTRAQ proteomics analysis was used to detect differentially expressed proteins between lymph node metastases and their paired primary tumor tissues from 23 patients with metastatic breast cancer. Immunohistochemistry was performed to validate the expression of two upregulated (EpCAM, FADD) and two downregulated (NDRG1, αB-crystallin) proteins in 190 paraffin-embedded tissue samples. These four proteins were further analyzed for their correlation with clinicopathological features in 190 breast cancer patients. We identified 637 differentially regulated proteins (397 upregulated and 240 downregulated) in lymph node metastases compared with their paired primary tumor tissues. Furthermore, bioinformatics analysis using GEO profiling confirmed the difference in the expression of EpCAM between metastases and primary tumors tissues. Two upregulated (EpCAM, FADD) and two downregulated (NDRG1, αB-crystallin) proteins were associated with the progression of breast cancer. Obviously, EpCAM plays a role in the metastasis of breast cancer cells to the lymph node. We further identified αB-crystallin as an independent biomarker to predict lymph node metastasis and the outcome of breast cancer patients.
2019-08-29 | PXD013931 | Pride