A5038828698- Ferroptosis and cancer prognosis
- Cancer Genomics and Diagnostics
- Cancer Immunotherapy and Biomarkers
- Hepatocellular Carcinoma Treatment and Prognosis
- Bioinformatics and Genomic Networks
- Immunotherapy and Immune Responses
- AI in cancer detection
- Hepatitis B Virus Studies
- Liver physiology and pathology
- Renal cell carcinoma treatment
- RNA modifications and cancer
- Renal and related cancers
- interferon and immune responses
- Colorectal Cancer Screening and Detection
- Radiomics and Machine Learning in Medical Imaging
- Microtubule and mitosis dynamics
- RNA Research and Splicing
- Endoplasmic Reticulum Stress and Disease
- Epigenetics and DNA Methylation
- Genetic factors in colorectal cancer
- Viral-associated cancers and disorders
- Cell Adhesion Molecules Research
- Immune cells in cancer
- Molecular Biology Techniques and Applications
- Nanoplatforms for cancer theranostics
Agency for Science, Technology and Research
2021-2024
Genome Institute of Singapore
2021-2024
Nanyang Technological University
2021-2024
The clinical relevance of immune landscape intratumoural heterogeneity (immune-ITH) and its role in tumour evolution remain largely unexplored. Here, we uncover significant spatial phenotypic immune-ITH from multiple sectors decipher relationship with disease progression hepatocellular carcinomas (HCC). Immune-ITH is associated transcriptomic-ITH, mutational burden distinct microenvironments. Tumours low experience higher immunoselective pressure escape via loss heterozygosity human...
While immune checkpoint blockade (ICB) has shown promise in patients with hepatocellular carcinoma (HCC), it is associated modest response rates and immune-related adverse events (irAEs) are common. In this study, we aimed to decipher trajectories mechanisms of and/or irAEs HCC receiving anti-programmed cell death 1 (anti-PD-1) therapy.Pre- on-treatment peripheral blood samples (n = 60) obtained from 32 (Singapore cohort) were analysed by cytometry time-of-flight single-cell RNA sequencing,...
Intra-tumor heterogeneity (ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic (transcriptomic and immune) heterogeneity. Using one of largest prospective surgical cohorts for hepatocellular carcinoma (HCC) with multi-region sampling, we sequenced whole genomes paired transcriptomes from 67 HCC patients (331 samples). We found that while ITH was rather constant across stages, had very different...
Abstract Solid tumors are complex ecosystems with heterogeneous 3D structures, but the spatial intra-tumor heterogeneity (sITH) at macroscopic (i.e., whole tumor) level is under-explored. Using a phylogeographic approach, we sequence genomes and transcriptomes from 235 spatially informed sectors across 13 hepatocellular carcinomas (HCC), generating one of largest datasets for studying sITH. We find that tumor in HCC segregates into variegated blocks large genotypic phenotypic differences. By...
Hepatocellular carcinoma (HCC) is a highly fatal cancer characterized by high intra-tumor heterogeneity (ITH). A panoramic understanding of its tumor evolution, in relation to clinical trajectory, may provide novel prognostic and treatment strategies.
Abstract A Disintegrin and Metalloproteinase with ThromboSpondin motif (ADAMTS) 5 functions as an anti-angiogenic anti-cancer protein independent of its metalloproteinase activity. Both full-length ADAMTS5 TS5-p45, the autocatalytically cleaved C-terminal 45 kDa truncate ADAMTS5, inhibits angiogenesis, induces endothelial cell (EC) apoptosis. However, how triggers EC apoptosis remains unclear. This work shows that caspase-8 (Cas-8) caspase-9 (Cas-9) are involved in TS5-p45-induced We...
Combination therapy with radioembolization (yttrium-90)-resin microspheres) followed by nivolumab has shown a promising response rate of 30.6% in Phase II trial (CA209-678) for advanced hepatocellular carcinoma (HCC); however, the mechanisms and relevant biomarkers remain unknown. By collecting both pretreatment on-treatment samples, we performed multimodal profiling tissue blood samples investigated molecular changes associated favorable responses 33 patients from trial. We found that...
A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21556-y.
Lifestyle and environmental-related exposures are important risk factors for hepatocellular carcinoma (HCC), suggesting that epigenetic dysregulation significantly underpins HCC. We profiled 30 surgically resected tumours the matched adjacent normal tissues to understand aberrant events associated with HCC.We identified tumour differential enhancers genes by analysing H3K27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) Hi-C/HiChIP data from samples of patients...
Conventional differential expression (DE) testing compares the grouped mean value of tumour samples to normal samples, and may miss out dysregulated genes in small subgroup patients. This is especially so for highly heterogeneous cancer like Hepatocellular Carcinoma (HCC).Using multi-region sampled RNA-seq data 90 patients, we performed patient-specific testing, together with patients' matched adjacent samples.Comparing results from conventional DE analysis analyses, show that omits some due...
Hepatocellular carcinoma (HCC) is one of the deadliest cancer types with diverse etiological factors across world.Although large scale genomic studies have been conducted in different countries, integrative analysis HCC genomes and ethnic comparison cohorts are lacking.Methods: We first integrated 1,349 patients from five world applied multiple statistical methods identifying driver genes.Subsequently, we systematically compared transcriptomes between Asians Europeans using TCGA...
As one of few viral-positive cancers, nasopharyngeal carcinoma (NPC) is extremely rare across the world but very frequent in several regions world, including Southern China (known as Cantonese cancer). Even though genomic studies have been conducted for NPC, their sample sizes are relatively small and systematic comparison with other cancer types has not explored. In this study, we collected four-hundred-thirty-one samples from six previous provided first integrative analysis NPC genomes....
Abstract The liver has a remarkable regenerative capacity. Nevertheless, under chronic liver-damaging conditions, this capacity becomes exhausted, allowing the accumulation of fibrotic tissue and leading to end-stage disease. Enhancing endogenous by targeting regeneration breaks is an innovative therapeutic approach. We set up in vivo functional genetic screen identify such breaks. As top hit, we identified Microfibril associated protein 4 (Mfap4). Knockdown Mfap4 hepatocytes enhances cell...
Abstract Tumor purity is the proportion of cancer cells in tumor tissue. An accurate estimation crucial for pathologic evaluation and sample selection to minimize normal cell contamination high throughput genomic analysis. We developed a novel deep multiple instance learning model predicting from H&E stained digital histopathology slides. Our successfully predicted slides fresh-frozen sections eight different TCGA cohorts formalin-fixed paraffin-embedded local Singapore cohort. The...
<h3>Background</h3> Multiple clinical trials have shown an overall improved response rate in hepatocellular carcinoma (HCC) by combining radiotherapy (RT) with immunotherapy (IO), however, treatment rates remain low and unpredictable.<sup>1</sup> The suboptimal outcomes are largely due to the lack of knowledge underlying immunomodulation effect effective treatment-response biomarker. Previous studies using tissue-based assays like multiplexed immunofluorescence (mIF) demonstrated that...
Proposed short titleY90-Resin Microspheres Radioembolization Followed by Nivolumab in Advanced Hepatocellular CarcinomaBackground : (N) and Y90-resin microspheres radioembolization (Y90-RE) aretherapeutic options advanced hepatocellular carcinoma (aHCC). Emerging evidence suggests synergy between radiotherapy immune checkpoint inhibitors. Methods Eligible Child-Pugh A aHCC patients were treated with Y90-RE followed N 240mg, 21 days after every 2 weeks thereafter. Pre- on-treatment tumor...
We present a case of 49-year Turkish woman who had synchronous renal leiomyoma and breast cancer.The patient was evaluated for suspicious mass; mass detected incidentally by contrast-enhanced computed tomography (CT).Diagnostic tru-cut biopsy performed both masses.Breast reported as invasive ductal carcinoma (IDC) while described benign mesenchymal tumour.According to the results, followed six months.For cancer, segmental mastectomy concomitant sentinel lymph node performed.Histologically,...