Project description:<p>Triple-negative breast cancer (TNBC) presents significant challenges to female</p><p>health owing to the lack of therapeutic targets and its poor prognosis. In recent</p><p>years, in the field of molecular pathology, there has been a growing focus on the</p><p>role of intra-tumoral microbial communities and metabolic alterations in tumor</p><p>cells. However, the precise mechanism through which microbiota and their</p><p>metabolites influence TNBC remains unclear and warrants further investigation.</p><p>In this study, we analyzed the microbial community composition in various</p><p>subtypes of breast cancer through 16S rRNA MiSeq sequencing of formalin-fixed,</p><p>paraffin-embedded (FFPE) tissue samples. Notably, Turicibacter, a microbe</p><p>associated with cancer response, exhibited a significantly higher abundance in</p><p>TNBC. Similarly, mass spectrometry-based metabolomic analysis revealed</p><p>substantial differences in specific metabolites, such as nutriacholic,</p><p>pregnanetriol, and cortol. Furthermore, we observed significant correlations</p><p>between the intra-tumoral</p>
Project description:Heterogeneity of gene expression profiles in head and neck cancer Background: Results of gene expression profiling studies from different institutes often lack consistency. This could be due to the use of different microarray platforms and protocols, or to intra-tumoral heterogeneity in mRNA expression. The aim of our study was to quantify intra-tumoral heterogeneity in head and cancer. Methods: Forty-four fresh frozen biopsies were taken from 22 patients, two per tumor. RNA was extracted, tested for quality, amplified, labeled and hybridized to a 35k oligoarray. Results: Unsupervised clustering analyses using all genes, the most variable genes, or random gene sets showed that 80-90% of biopsy pairs clustered together. A within-pair-between-pair scatter ratio analysis showed that the similarity between matching pairs was significantly greater than that between random pairs (p < 0.00001). Conclusions: Two biopsies from the same tumor show far greater similarity in gene expression than biopsies from different tumors, supporting the use of one biopsy for expression profiling.
Project description:IFN gamma signaling in cytotoxic T cells restricts antitumor responses by inhibiting the maintenance and clonality of intra-tumoral stem-like T cells
Project description:Glioblastoma multiforme (GBM) is a highly heterogeneous disease that shows an enourmous range of genetic abnormalities in comparison to other astrocytic tumors. Intra-patient heterogeneity in GBM has been poorly characterized both at phenotypic and genomic level. During surgical GBM resections, we have extracted between 4 and 8 tumor subsamples from different areas of the malignant tissue that were at least 1cm apart. Our aim to asses the intra-tumoral heterogeneity at the gene expression level to uncover important dynamics underlying GBM progression that may have relevant implication for treatment.
Project description:Glioblastoma (GBM) is an aggressive form of brain cancer with well-established patterns of intra-tumoral heterogeneity implicated in treatment resistance, recurrence and progression. While regional and single cell transcriptomic variations of GBM have been recently resolved, downstream phenotype-level proteomic programs have yet to be assigned to specific niches. Here, we leverage mass spectrometry to spatially align abundance levels of 4,794 proteins to GBM’s hallmark histomorphologic niches across 20 patients and define distinct molecular programs operational within these regional tumor compartments. Using machine learning, we overlay concordant transcriptional information, and define two distinct proteogenomic programs, MYC- and KRAS-axis hereon, that cooperate with hypoxia to produce a tri-dimensional model of intra-tumoral heterogeneity. Importantly, we show using multiple cohorts, that GBMs with an enhanced KRAS component harbor a more clinically aggressive and infiltrative phenotype. Conversely, tumor cells enriched along the MYC axis where mutually exclusive and had a distinct proliferative program. Moreover, by applying both experimental and computational approaches to link each of these distinct molecular axes with potential pharmacological therapies, we highlight differential drug sensitivities and a notable relative chemoresistance in GBM cell lines with enhanced KRAS programs. Importantly, pharmacological differences were less evident when using traditional expression-based subgroups supporting thattopographic phenotypic mapping ofGBM, and the proposed axes may provide new insights for targeting heterogeneity and overcoming therapy resistance in this aggressive disease.
Project description:Glioblastoma multiforme (GBM) is a highly heterogeneous disease that shows an wide range of genetic abnormalities in comparison to other astrocytic tumors. We have extracted between 4 and 8 tumor subsamples from different areas of the malignant tissue that were at least 1cm apart. Our aim to asses the intra-tumoral heterogeneity by comparing copy number aberrations in different tumor areas to uncover important dynamics underlying GBM progression.
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.