Project description:Neuroblastoma, a deadly pediatric cancer from the sympathetic ganglia of the peripheral nervous system, frequently metastasizes, driving poor outcomes in high-risk cases. While primary tumors are well-characterized, the cellular and molecular dynamics of metastasis remain poorly understood. Here, we employed single-cell multi-omics and spatial transcriptomics to profile lymph node metastases in high-risk neuroblastoma compared to primary adrenal masses. We found that lymph node metastases displayed unique cellular heterogeneity and plasticity marked by a shift toward mesenchymal-like and cancer stem cell states, with enriched epithelial-to-mesenchymal transition (EMT) programs. Lymph node metastatic niche exhibited altered tumor microenvironment dynamics, characterized by increased immunosuppressive myeloid subsets, heightened immune checkpoint signaling and lymphocyte exhaustion, indicative of immune evasion and dysfunction. Our multi-omics studies reveal distinct features of high-risk neuroblastoma that contribute to metastasis and therapy resistance, pointing to potential therapeutic vulnerabilities of the aggressive metastatic disease.
Project description:Neuroblastoma, a deadly pediatric cancer from the sympathetic ganglia of the peripheral nervous system, frequently metastasizes, driving poor outcomes in high-risk cases. While primary tumors are well-characterized, the cellular and molecular dynamics of metastasis remain poorly understood. Here, we employed single-cell multi-omics and spatial transcriptomics to profile lymph node metastases in high-risk neuroblastoma compared to primary adrenal masses. We found that lymph node metastases displayed unique cellular heterogeneity and plasticity marked by a shift toward mesenchymal-like and cancer stem cell states, with enriched epithelial-to-mesenchymal transition (EMT) programs. Lymph node metastatic niche exhibited altered tumor microenvironment dynamics, characterized by increased immunosuppressive myeloid subsets, heightened immune checkpoint signaling and lymphocyte exhaustion, indicative of immune evasion and dysfunction. Our multi-omics studies reveal distinct features of high-risk neuroblastoma that contribute to metastasis and therapy resistance, pointing to potential therapeutic vulnerabilities of the aggressive metastatic disease.
Project description:Neuroblastoma, a deadly pediatric cancer from the sympathetic ganglia of the peripheral nervous system, frequently metastasizes, driving poor outcomes in high-risk cases. While primary tumors are well-characterized, the cellular and molecular dynamics of metastasis remain poorly understood. Here, we employed single-cell multi-omics and spatial transcriptomics to profile lymph node metastases in high-risk neuroblastoma compared to primary adrenal masses. We found that lymph node metastases displayed unique cellular heterogeneity and plasticity marked by a shift toward mesenchymal-like and cancer stem cell states, with enriched epithelial-to-mesenchymal transition (EMT) programs. Lymph node metastatic niche exhibited altered tumor microenvironment dynamics, characterized by increased immunosuppressive myeloid subsets, heightened immune checkpoint signaling and lymphocyte exhaustion, indicative of immune evasion and dysfunction. Our multi-omics studies reveal distinct features of high-risk neuroblastoma that contribute to metastasis and therapy resistance, pointing to potential therapeutic vulnerabilities of the aggressive metastatic disease.
Project description:Angiogenesis plays a key role in tumor metastasis. Many genes may act in this process including formation of vessels, immune evasion,etc. Different gene expression profiles between lymphoma endothelium cells and reactive lymph node-derived endothelium cells may uncover these genes. And intensive mechanism researches on such key genes may explain the mechanisim of tumor-specific angiogenesis and help to explore effective treatment strategies to prevent/reverse tumor metastasis. We use microarrays to detail gene expression profiles of human lymphoma endothelium and reactive lymph node-derived endothelium. Lymph nodes were taken from surgery samples of cases pathologically diagnosed DLBCL (diffuse large B-cell lymphoma), PTL (peripheral T cell lymphoma) and reactive lymph nodes. The pure endothelium cells were isolated by LCM after immunohistochemical staining of CD34. We found Tim-3 was preferentially expressed on lymphoma-derived ECs via different expression profiles between lymphoma ECs and reactive lymph node-derived ECs. Intensive researches were carried out on Tim-3-expressing -ECs and we found that Tim-3 -expressing-Ecs may play important role on EC-mediated tumor evasion.
Project description:Immune system plays a dual role in cancer by either targeting or supporting neoplastic cells at various stages of disease, including metastasis. Yet, the exact immune-related transcriptome profiles of breast cancer cells and their evolution during dissemination remain undiscovered. This study aimed at exploring immune-related transcriptomic landscape of primary tumors and lymph node metastasis of chemotherapy-naïve breast cancer patients.
Project description:Angiogenesis plays a key role in tumor metastasis. Many genes may act in this process including formation of vessels, immune evasion,etc. Different gene expression profiles between lymphoma endothelium cells and reactive lymph node-derived endothelium cells may uncover these genes. And intensive mechanism researches on such key genes may explain the mechanisim of tumor-specific angiogenesis and help to explore effective treatment strategies to prevent/reverse tumor metastasis. We use microarrays to detail gene expression profiles of human lymphoma endothelium and reactive lymph node-derived endothelium.
Project description:Lymph node status is a crucial predictor for the overall survival of invasive breast cancer. However, lymph node involvement is only detected in about half of HER2 positive patients. Currently, there are no biomarkers available for distinguishing small size HER2-positive breast cancers with different lymph node statuses. Thus, in the present study, we applied label-free quantitative proteomic strategy to construct plasma proteomic profiles of ten patients with small size HER2-positive breast cancers (5 patients with lymph node metastasis versus 5 patients with lymph node metastasis).
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
Project description:We performed single cell RNA sequencing (RNA-seq) for 549 primary breast cancer cells and lymph node metastases from 11 patients with distinct molecular subtypes (BC01-BC02, estrogen receptor positive (ER+); BC03, double positive (ER+ and HER2+); BC03LN, lymph node metastasis of BC03; BC04-BC06, human epidermal growth factor receptor 2 positive (HER2+); BC07-BC11, triple-negative breast cancer (TNBC); BC07LN, lymph node metastasis of BC07) and matched bulk tumors. We separated these single cells into epithelial tumor and tumor-infiltrating immune cells using inferred CNVs from RNA-seq. The refined single cell profiles for the tumor and immune cells provide key expression signatures of breast cancer and the surrounding microenvironment.
Project description:Identifying the exact molecules associated with CRC metastasis may be crucial to understand the process, which might also be translated to the diagnosis and treatment of CRC. In this study, we investigate the association of microRNA expression patterns with the lymph node metastasis of colorectal cancer. To investigate the association of microRNA expression patterns with the lymph node metastasis of colorectal cancer, eight primary colorectal cancer tissues derived from stage II–III colorectal cancer patients with (n = 4) or without (n = 4) lymph node metastasis were collected and the miRNA expression profiles of them were determined using Agilent miRNA microarray. Different miRNA expression profiles were identified in CRC tissues between lymph node metastasis positive and negative group.