ABSTRACT: Intra-tumoral heterogeneity in metastatic potential and survival signaling between iso-clonal HCT116 and HCT116b human colon carcinoma cell lines
Project description:Characterization of the intra-tumoral heterogeneity between two iso-clonal human colon cancer sublines HCT116 and HCT116b on their ability to undergo metastatic colonization and survive under growth factor deprivation stress (GFDS). Microarray analysis revealed an upregulation of survival and metastatic genes in the highly metastatic HCT116 primary colon tumor cells compared to the poorly metastatic HCT116b primary colon tumor cells.
Project description:Characterization of the intra-tumoral heterogeneity between two iso-clonal human colon cancer sublines HCT116 and HCT116b on their ability to undergo metastatic colonization and survive under growth factor deprivation stress (GFDS). Microarray analysis revealed an upregulation of survival and metastatic genes in the highly metastatic HCT116 primary colon tumor cells compared to the poorly metastatic HCT116b primary colon tumor cells. Total RNA obtained from isolated primary colon tumors of HCT116 and HCT116b xenograft transplanted animals obtained using the orthotopic implantation of HCT116 and HCT116b human colon cancer xenografts in the cecum of male athymic BALB/c nude mice were compared at their gene expression level.
Project description:Almost half of all patients diagnosed with colorectal cancer develop liver metastases. The potential role of intra-individual metastatic heterogeneity remains poorly characterized. By high-resolution DNA copy number analyses and a novel approach based on pair-wise genetic distance, we examined the genetic heterogeneity among multiple liver metastatic deposits obtained from 45 patients subject to curative liver resection. We found large variation in intra-individual metastatic heterogeneity. A high level of heterogeneity was associated with poor patient survival. Patients with metachronous metastases who received chemotherapy had significantly more heterogeneity than chemonaïve patients.
Project description:Melanoma brain metastasis (MBM) response to treatment varies greatly among patients, affecting overall prognosis and survival. This study aims to provide a comprehensive multi-omics overview of MBM by investigating tumor tissue composition at spatial, proteomic and transcriptomic levels, elucidating the spatial tumor landscape, characterizing tumor tissue cell populations and identifying enriched signaling pathways in the MBM tumor tissue. We found higher inter-tumoral heterogeneity than intra-tumoral heterogeneity in MBM at the protein and transcriptional levels. The treatment-naive patient exhibited high intra-tumoral heterogeneity (ITH) compared to patient who received treatment, with ITH levels varying across neighboring regions in all patient tumors. Significant global protein and cell type enrichment associated with malignant cells, macrophages, CAFs, and immune cells was observed in MBM using cellular deconvolution and tumor microenvironment (TME) analysis. The presence of MBM cell-type specific gene signatures, and enriched pathways identified using ST and bulk-seq provide an essential framework for understanding tumor composition and potential treatment-related effects in each MBM patient tumor. Taken together, our results provide a comprehensive spatial and molecular view of intra-tumoral and inter-tumoral heterogeneity in MBM, potentially guiding personalized treatment strategies in MBM therapy.
Project description:Deciphering intra- and inter-tumoral heterogeneity is essential for understanding gastric cancer (GC) biology and identifying effective therapeutic targets. We used single-cell RNA sequencing (scRNA-seq) to reveal the transcriptional heterogeneity of diverse cells within primary and metastatic GC and their roles in disease progression.
Project description:Metastatic prostate cancer (mPC) is a clinically and molecularly heterogeneous disease. While there is increasing recognition of diverse tumor phenotypes across patients, less is known about the molecular and phenotypic heterogeneity present within an individual. In this study, we aimed to define the patterns, extent, and consequences of inter- and intra-tumoral heterogeneity in lethal prostate cancer. By combining and integrating in situ tissue-based and sequencing approaches, we analyzed over 630 tumor samples from 52 mPC patients. Our efforts revealed phenotypic heterogeneity at the patient, metastasis, and cellular levels. We observed that intra-patient, inter-tumoral molecular subtype heterogeneity was common in mPC and showed associations with genomic and clinical features. Additionally, cellular proliferation rates varied within a given patient across molecular subtypes and anatomic sites. Single-cell sequencing studies revealed features of morphologically and molecularly divergent tumor cell populations within a single metastatic site. These data provide a deeper insight into the complex patterns of tumoral heterogeneity in mPC with implications for clinical management and the future development of diagnostic and therapeutic approaches.
Project description:Metastatic prostate cancer (mPC) is a clinically and molecularly heterogeneous disease. While there is increasing recognition of diverse tumor phenotypes across patients, less is known about the molecular and phenotypic heterogeneity present within an individual. In this study, we aimed to define the patterns, extent, and consequences of inter- and intra-tumoral heterogeneity in lethal prostate cancer. By combining and integrating in situ tissue-based and sequencing approaches, we analyzed over 630 tumor samples from 52 mPC patients. Our efforts revealed phenotypic heterogeneity at the patient, metastasis, and cellular levels. We observed that intra-patient, inter-tumoral molecular subtype heterogeneity was common in mPC and showed associations with genomic and clinical features. Additionally, cellular proliferation rates varied within a given patient across molecular subtypes and anatomic sites. Single-cell sequencing studies revealed features of morphologically and molecularly divergent tumor cell populations within a single metastatic site. These data provide a deeper insight into the complex patterns of tumoral heterogeneity in mPC with implications for clinical management and the future development of diagnostic and therapeutic approaches.
Project description:Our study provides a comprehensive multiomics overview of each patient’s tumor, revealing tumor cell types, proteomics, and transcriptomic changes related to melanoma brain metastasis (MBM). Here, we have applied the HiRIEF pre-fractionation and tandem mass tags (TMT)-16plex based peptide quantification to generate proteomes of multiple neighboring regions within each MBM tumor tissue. PCA and Hierarchical clustering analysis illustrated higher inter-tumoral heterogeneity than intra-tumoral heterogeneity of MBM at the protein levels, as lesions from the same patients are grouped into a single cluster. The treatment-naive patient (P3) exhibited high intra-tumoral heterogeneity (ITH) compared to treated ones, with ITH levels varying across neighboring regions in patient tumors. Differential expression analysis highlighted enriched protein and gene clusters for all patient comparisons, including innate immune proteins, macrophage activation, T- and B-cell signaling, and key cancer pathways (e.g., epithelial-mesenchymal transition, cell adhesion, notch signaling, oxidative phosphorylation and cell cycle checkpoints). Genes involved in functional processes characteristic of MBM cell types, tumor-immune interactions, and signaling mechanisms were more highly correlated with their protein levels. Overall, our results provide a comprehensive spatial and molecular view of intra-tumoral and inter-tumoral heterogeneity in MBM.
Project description:Our study provides a comprehensive multiomics overview of each patient’s tumor, revealing tumor cell types, proteomics, and transcriptomic changes related to melanoma brain metastasis (MBM). Here, we have applied the HiRIEF pre-fractionation and tandem mass tags (TMT)-16plex based peptide quantification to generate proteomes of multiple neighboring regions within each MBM tumor tissue. PCA and Hierarchical clustering analysis illustrated higher inter-tumoral heterogeneity than intra-tumoral heterogeneity of MBM at the protein levels, as lesions from the same patients are grouped into a single cluster. The treatment-naive patient (P3) exhibited high intra-tumoral heterogeneity (ITH) compared to treated ones, with ITH levels varying across neighboring regions in patient tumors. Differential expression analysis highlighted enriched protein and gene clusters for all patient comparisons, including innate immune proteins, macrophage activation, T- and B-cell signaling, and key cancer pathways (e.g., epithelial-mesenchymal transition, cell adhesion, notch signaling, oxidative phosphorylation and cell cycle checkpoints). Genes involved in functional processes characteristic of MBM cell types, tumor-immune interactions, and signaling mechanisms were more highly correlated with their protein levels. Overall, our results provide a comprehensive spatial and molecular view of intra-tumoral and inter-tumoral heterogeneity in MBM.
Project description:Our study provides a comprehensive multiomics overview of each patient’s tumor, revealing tumor cell types, proteomics, and transcriptomic changes related to melanoma brain metastasis (MBM). Here, we have applied the HiRIEF pre-fractionation and tandem mass tags (TMT)-16plex based peptide quantification to generate proteomes of multiple neighboring regions within each MBM tumor tissue. PCA and Hierarchical clustering analysis illustrated higher inter-tumoral heterogeneity than intra-tumoral heterogeneity of MBM at the protein levels, as lesions from the same patients are grouped into a single cluster. The treatment-naive patient (P3) exhibited high intra-tumoral heterogeneity (ITH) compared to treated ones, with ITH levels varying across neighboring regions in patient tumors. Differential expression analysis highlighted enriched protein and gene clusters for all patient comparisons, including innate immune proteins, macrophage activation, T- and B-cell signaling, and key cancer pathways (e.g., epithelial-mesenchymal transition, cell adhesion, notch signaling, oxidative phosphorylation and cell cycle checkpoints). Genes involved in functional processes characteristic of MBM cell types, tumor-immune interactions, and signaling mechanisms were more highly correlated with their protein levels. Overall, our results provide a comprehensive spatial and molecular view of intra-tumoral and inter-tumoral heterogeneity in MBM.