How tumor microenvironmental forces shape plasticity of cancer cell morphology is poorly understood. Here, we conduct automated histology image and spatial statistical analyses in 514 high grade serous ovarian samples to define cancer morphological diversification within the spatial context of the microenvironment. Tumor spatial zones, where cancer cell nuclei diversify in shape, are mapped in each tumor. Integration of this spatially explicit analysis with omics and clinical data reveals a relationship between morphological diversification and the dysregulation of DNA repair, loss of nuclear integrity, and increased disease mortality. Within the Immunoreactive subtype, spatial analysis further reveals significantly lower lymphocytic infiltration within diversified zones compared with other tumor zones, suggesting that even immune-hot tumors contain cells capable of immune escape. Our findings support a model whereby a subpopulation of morphologically plastic cancer cells with dysregulated DNA repair promotes ovarian cancer progression through positive selection by immune evasion.
The Open Microscopy Environment (OME) Data Model and XML file: open tools for informatics and quantitative analysis in biological imaging
Galectin-3 expression correlates with apoptosis of tumor-associated lymphocytes in human melanoma biopsies.
Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition
The nucleoporin Nup153 has separable roles in both early mitotic progression and the resolution of mitosis.
Differential protein mapping of ovarian serous adenocarcinomas: identification of potential markers for distinct tumor stage.
The nucleoporin Nup153 maintains nuclear envelope architecture and is required for cell migration in tumor cells
Proteomics profiling of microdissected low- and high-grade prostate tumors identifies Lamin A as a discriminatory biomarker
Mechanical signaling through the cytoskeleton regulates cell proliferation by coordinated focal adhesion and Rho GTPase signaling
The interaction between nesprins and sun proteins at the nuclear envelope is critical for force transmission between the nucleus and cytoskeleton.
The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data.
Quantitative image analysis of cellular heterogeneity in breast tumors complements genomic profiling
New strategies in the treatment of ovarian cancer: current clinical perspectives and future potential
AbsCN-seq: a statistical method to estimate tumor purity, ploidy and absolute copy numbers from next-generation sequencing data
A nonlinear mapping approach to stain normalization in digital histopathology images using image-specific color deconvolution
Prognostic B-cell signatures using mRNA-seq in patients with subtype-specific breast and ovarian cancer
Integrating mapping-, assembly- and haplotype-based approaches for calling variants in clinical sequencing applications
Combined image and genomic analysis of high-grade serous ovarian cancer reveals PTEN loss as a common driver event and prognostic classifier
Up-regulation of circ_LARP4 suppresses cell proliferation and migration in ovarian cancer by regulating miR-513b-5p/LARP4 axis
Topological Tumor Graphs: A Graph-Based Spatial Model to Infer Stromal Recruitment for Immunosuppression in Melanoma Histology.
Sonodynamic Therapy Combined to 2-Deoxyglucose Potentiate Cell Metastasis Inhibition of Breast Cancer
Genomic and Transcriptomic Determinants of Therapy Resistance and Immune Landscape Evolution during Anti-EGFR Treatment in Colorectal Cancer
Systemic Analysis of the DNA Replication Regulator MCM Complex in Ovarian Cancer and Its Prognostic Value.
Machine Learning and Artificial Intelligence-driven Spatial Analysis of the Tumor Immune Microenvironment in Pathology Slides.
Analysis of tumour ecological balance reveals resource-dependent adaptive strategies of ovarian cancer
Breast Cancer: BRCA1 & BRCA2
Mutations involving BRCA1, found on chromosome 17, and BRCA2, found on chromosome 13, increase the risk for specific cancers, such as breast cancer. Discover the last research on breast cancer BRCA1 and BRCA2 here.