Cell, Год журнала: 2020, Номер 180(5), С. 915 - 927.e16
Опубликована: Фев. 20, 2020
Язык: Английский
Scientific Reports, Год журнала: 2021, Номер 11(1)
Опубликована: Март 15, 2021
Abstract Cancer hallmark genes are responsible for the most essential phenotypic characteristics of malignant transformation and progression. In this study, our aim was to estimate prognostic effect established cancer in multiple distinct types. RNA-seq HTSeq counts survival data from 26 different tumor types were acquired TCGA repository. DESeq used normalization. Correlations between gene expression computed using Cox proportional hazards regression by plotting Kaplan–Meier plots. The false discovery rate calculated correct hypothesis testing. Signatures based on involved genome instability invasion reached significance individual Thyroid glioblastoma independent (61 54 significant, respectively), while renal clear cell low grade gliomas harbored changes (403 419 respectively). eight with highest included BRCA1 (genome instability, HR 4.26, p < 1E−16), RUNX1 (sustaining proliferative signaling, 2.96, = 3.1E−10) SERPINE1 (inducing angiogenesis, 3.36, 1.5E−12) glioma, CDK1 (cell death resistance, 5.67, 2.1E−10) kidney papillary carcinoma, E2F1 (tumor suppressor, 0.38, 2.4E−05) EREG (enabling replicative immortality, 3.23, 2.1E−07) cervical cancer, FBP1 (deregulation cellular energetics, 0.45, 2.8E−07) carcinoma MYC (invasion metastasis, 1.81, 5.8E−05) bladder cancer. We observed unexpected heterogeneity tissue specificity when correlating survival. These results will help prioritize future targeted therapy development solid tumors.
Язык: Английский
Процитировано
1022
Nature reviews. Cancer, Год журнала: 2020, Номер 20(10), С. 555 - 572
Опубликована: Авг. 10, 2020
Язык: Английский
Процитировано
987
Nature, Год журнала: 2020, Номер 577(7789), С. 179 - 189
Опубликована: Янв. 8, 2020
Язык: Английский
Процитировано
600
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2018, Номер unknown
Опубликована: Май 18, 2018
Abstract UCSC Xena is a visual exploration resource for both public and private omics data, supported through the web-based Browser multiple turn-key Hubs. This unique archecture allows researchers to view their own data securely, using Hubs, simultaneously visualizing large cancer genomics datasets, including TCGA GDC. Data integration occurs only within Browser, keeping private. supports virtually any functional SNVs, INDELs, structural variants, CNV, expression, DNA methylation, ATAC-seq signals, phenotypic annotations. features include Visual Spreadsheet, survival analyses, powerful filtering subgrouping, statistical genomic signatures, bookmarks. differentiates itself from other tools, its predecessor, Cancer Genomics by ability easily securely high performance, broad type support, many features.
Язык: Английский
Процитировано
444
Cancer Discovery, Год журнала: 2021, Номер 11(4), С. 900 - 915
Опубликована: Апрель 1, 2021
Artificial intelligence (AI) is rapidly reshaping cancer research and personalized clinical care. Availability of high-dimensionality datasets coupled with advances in high-performance computing, as well innovative deep learning architectures, has led to an explosion AI use various aspects oncology research. These applications range from detection classification cancer, molecular characterization tumors their microenvironment, drug discovery repurposing, predicting treatment outcomes for patients. As these start penetrating the clinic, we foresee a shifting paradigm care becoming strongly driven by AI. SIGNIFICANCE: potential dramatically affect nearly all oncology-from enhancing diagnosis personalizing discovering novel anticancer drugs. Here, review recent enormous progress application oncology, highlight limitations pitfalls, chart path adoption clinic.
Язык: Английский
Процитировано
436
Cell, Год журнала: 2022, Номер 185(3), С. 563 - 575.e11
Опубликована: Фев. 1, 2022
Язык: Английский
Процитировано
422
Cell Metabolism, Год журнала: 2022, Номер 35(1), С. 84 - 100.e8
Опубликована: Окт. 17, 2022
Treatment of triple-negative breast cancer (TNBC) remains challenging. Deciphering the orchestration metabolic pathways in regulating ferroptosis will provide new insights into TNBC therapeutic strategies. Here, we integrated multiomics data our large cohort (n = 465) to develop atlas. We discovered that TNBCs had heterogeneous phenotypes ferroptosis-related metabolites and pathways. The luminal androgen receptor (LAR) subtype was characterized by upregulation oxidized phosphatidylethanolamines glutathione metabolism (especially GPX4), which allowed utilization GPX4 inhibitors induce ferroptosis. Furthermore, verified inhibition not only induced tumor but also enhanced antitumor immunity. combination anti-PD1 possessed greater efficacy than monotherapy. Clinically, higher expression correlated with lower cytolytic scores worse prognosis immunotherapy cohorts. Collectively, this study demonstrated landscape revealed an innovative strategy for refractory LAR tumors.
Язык: Английский
Процитировано
311
Cancer Cell, Год журнала: 2019, Номер 35(2), С. 177 - 190.e8
Опубликована: Янв. 27, 2019
Язык: Английский
Процитировано
253
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2020, Номер unknown
Опубликована: Ноя. 16, 2020
ABSTRACT Cancer hallmark genes are responsible for the most essential phenotypic characteristics of malignant transformation and progression. In this study, our aim was to estimate prognostic effect established cancer in multiple distinct types. RNA-seq HTSeq counts survival data from 26 different tumor types were acquired TCGA repository. DESeq used normalization. Correlations between gene expression computed using Cox proportional hazards regression by plotting Kaplan-Meier plots. The false discovery rate calculated correct hypothesis testing. Signatures based on involved genome instability invasion reached significance individual Thyroid glioblastoma independent (61 54 significant, respectively), while renal clear cell low grade gliomas harbored changes (403 419 respectively). eight with highest included BRCA1 (genome instability, HR=4.26, p<1E-16), RUNX1 (sustaining proliferative signaling, HR=2.96, p=3.1E-10) SERPINE1 (inducing angiogenesis, HR=3.36, p=1.5E-12) glioma, CDK1 (cell death resistance, HR=5.67, p=2.1E-10) kidney papillary carcinoma, E2F1 (tumor suppressor, HR=0.38, p=2.4E-05) EREG (enabling replicative immortality, HR=3.23, p=2.1E-07) cervical cancer, FBP1 (deregulation cellular energetics, HR=0.45, p=2.8E-07) carcinoma MYC (invasion metastasis, HR=1.81, p=5.8E-05) bladder cancer. We observed unexpected heterogeneity tissue specificity when correlating survival. These results will help prioritize future targeted therapy development solid tumors.
Язык: Английский
Процитировано
241
Molecular Therapy, Год журнала: 2020, Номер 28(11), С. 2358 - 2366
Опубликована: Сен. 2, 2020
System xc- cystine/glutamate antiporter, composed of a light-chain subunit (xCT, SLC7A11) and heavy-chain (CD98hc, SLC3A2), is mainly responsible for the cellular uptake cystine in exchange intracellular glutamate. In recent years, xCT molecule has been found to play an important role tumor growth, progression, metastasis, multidrug resistance various types cancer. Interestingly, also exhibits essential function regulating tumor-associated ferroptosis. Despite significant progress targeting system transporter cancer treatment, underlying mechanisms still remain elusive. It unclear why solid tumors are more sensitive inhibitors such as sulfasalazine, compared hematological malignancies. This review focuses on regard chemoresistance, tumor-selective ferroptosis, gene expression. The potential therapeutic implications its combination with chemotherapeutic agents or immunotherapy suppress growth overcome drug discussed.
Язык: Английский
Процитировано
234