An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Egypt’s Failed Democratic Transition: Why the Labour Movement Matters

This article analyses the failure of Egypt’s democratic transition between 2011 and 2013, highlighting the often-overlooked role of the labour movement. While dominant approaches in transition studies emphasise socio-economic factors, elite dynamics or the middle class, this study argues that the absence of an independent labour movement rooted in the industrial working class critically undermined Egypt’s prospects for democratic consolidation. Drawing on interviews with Egyptian trade unionists and relevant literature, the article uses process-tracing to situate the Egyptian experience within broader debates on democratisation. It contrasts this experience with transitions in Tunisia, Brazil, South Africa, Poland and South Korea—where labour movements were central actors. Challenging modernisation theory and elite-focused models, it adopts an actor-centred perspective that foregrounds organised labour. The article concludes that although Egypt’s working class played a key role in mobilising dissent, it lacked the institutional strength to shape the transition. The Egyptian case underscores the enduring relevance of labour movements, especially in an era of democratic backsliding and neoliberal fragmentation

Multiphoton Grin Endoscopy For Real-Time Diagnosis Of Diseased Tissue

Multiphoton microscopy has the potential to become a valuable tool for clinical diagnosis of tissue health. It has the ability to provide images with similar cellular and architectural tissue information to the gold standard for tissue diagnosis, histopathological analysis of biopsies. However, unlike histopathology, it can provide these images in real time in unstained and unprocessed tissue in vivo. Due to the depth limitations of multiphoton microscopy, endoscopic access to the tissue is required for this technology to be clinically useful. This dissertation details our efforts to translate multiphoton microscopy into the clinical field through the development of a GRIN lens based multiphoton endoscopic prototype. As compared to other endoscopic approaches, GRIN lenses, while rigid, provide several advantages, including small diameters (down to 0.350 mm), no need to miniaturize excitation and collection optics, low manufacturing costs and potential compatibility with existing biopsy instrumentation. In this dissertation we initially show that multiphoton imaging through long (up to 285 mm) GRIN lens endoscope systems is possible. We then design fabricate a portable, rigid endoscope system suitable for imaging unstained tissues, potentially deep within the body, using a GRIN lens system of 1 mm diameter and 8 cm length.     The portable device is capable of imaging a ~200 [mu]m diameter field of view at 4 frames/s. The lateral and axial resolution in water is 0.85 [mu]m and 7.4 [mu]m respectively. We demonstrate the capabilities of our device through in vivo imaging of unstained tissues in live, anesthetized rats. We further show compatibility of this device with three photon excitation. Finally, we test the diagnostic capabilities of our prototype on human prostate cancer samples ex vivo. The presented results show great promise for GRIN endoscopy to become a valuable tool clinically both for the diagnosis of tissue health and to aid during surgeries by identifying tumor margins and other tissue architecture