BMC Genomics, Journal Year: 2022, Volume and Issue: 23(1)
Published: Feb. 15, 2022
The collective of somatic mutations in a genome represents record mutational processes that have been operative cell. These can be investigated by extracting relevant patterns from sequencing data.
Language: Английский
Cell Research, Journal Year: 2019, Volume and Issue: 29(9), P. 725 - 738
Published: July 4, 2019
Language: Английский
Citations
963
Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)
Published: March 12, 2020
The epigenetic regulation of immune response has been demonstrated in recent studies. Nonetheless, potential roles RNA N6-methyladenosine (m6A) modification tumor microenvironment (TME) cell infiltration remain unknown.We comprehensively evaluated the m6A patterns 1938 gastric cancer samples based on 21 regulators, and systematically correlated these with TME cell-infiltrating characteristics. m6Ascore was constructed to quantify individual tumors using principal component analysis algorithms.Three distinct were determined. characteristics under three highly consistent phenotypes including immune-excluded, immune-inflamed immune-desert phenotypes. We evaluation within could predict stages inflammation, subtypes, stromal activity, genetic variation, patient prognosis. Low m6Ascore, characterized by increased mutation burden activation immunity, indicated an inflamed phenotype, 69.4% 5-year survival. Activation stroma lack effective observed high subtype, indicating a non-inflamed immune-exclusion poorer also linked neoantigen load enhanced anti-PD-1/L1 immunotherapy. Two immunotherapy cohorts confirmed patients lower significant therapeutic advantages clinical benefits.This work revealed played nonnegligible role formation diversity complexity. Evaluating pattern will contribute enhancing our cognition characterization guiding more strategies.
Language: Английский
Citations
789
Nature, Journal Year: 2019, Volume and Issue: 567(7747), P. 257 - 261
Published: Feb. 27, 2019
Language: Английский
Citations
760
Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12
Published: July 2, 2021
Recent advances in next-generation sequencing (NGS) technologies have triggered the rapid accumulation of publicly available multi-omics datasets. The application integrated omics to explore robust signatures for clinical translation is increasingly emphasized, and this attributed success immune checkpoint blockades diverse malignancies. However, effective tools comprehensively interpreting data are still warranted provide increased granularity into intrinsic mechanism oncogenesis immunotherapeutic sensitivity. Therefore, we developed a computational tool Immuno-Oncology Biological Research (IOBR), providing comprehensive investigation estimation reported or user-built signatures, TME deconvolution, signature construction based on data. Notably, IOBR offers batch analyses these their correlations with phenotypes, long non-coding RNA (lncRNA) profiling, genomic characteristics, generated from single-cell (scRNA-seq) different cancer settings. Additionally, integrates multiple existing microenvironmental deconvolution methodologies convenient comparison selection. Collectively, user-friendly leveraging facilitate immuno-oncology exploration unveil tumor-immune interactions accelerating precision immunotherapy.
Language: Английский
Citations
758
Cell, Journal Year: 2020, Volume and Issue: 183(5), P. 1436 - 1456.e31
Published: Nov. 1, 2020
The integration of mass spectrometry-based proteomics with next-generation DNA and RNA sequencing profiles tumors more comprehensively. Here this "proteogenomics" approach was applied to 122 treatment-naive primary breast cancers accrued preserve post-translational modifications, including protein phosphorylation acetylation. Proteogenomics challenged standard cancer diagnoses, provided detailed analysis the ERBB2 amplicon, defined tumor subsets that could benefit from immune checkpoint therapy, allowed accurate assessment Rb status for prediction CDK4/6 inhibitor responsiveness. Phosphoproteomics uncovered novel associations between suppressor loss targetable kinases. Acetylproteome highlighted acetylation on key nuclear proteins involved in damage response revealed cross-talk cytoplasmic mitochondrial metabolism. Our results underscore potential proteogenomics clinical investigation through annotation pathways biological features remarkably heterogeneous malignancy.
Language: Английский
Citations
404
Cell, Journal Year: 2021, Volume and Issue: 184(1), P. 226 - 242.e21
Published: Jan. 1, 2021
Language: Английский
Citations
357
Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)
Published: April 14, 2021
Abstract Breast cancer is a heterogeneous pathology, but the genomic basis of its variability remains poorly understood in populations other than Caucasians. Here, through DNA and RNA portraits we explored molecular features breast cancers set Hispanic-Mexican (HM) women compared them to public multi-ancestry datasets. HM patients present an earlier onset disease, particularly aggressive clinical subtypes, non-Hispanic women. The age-related COSMIC signature 1 was more frequent those from ancestries. We found AKT1 E17K hotspot mutation 8% identify AKT1/PIK3CA axis as potentially druggable target. Also, luminal tumors enhanced immunogenic phenotype Asiatic Caucasian tumors. This study initial effort include Hispanic research etiology biology further understand disparities.
Language: Английский
Citations
285
Cell, Journal Year: 2020, Volume and Issue: 182(1), P. 226 - 244.e17
Published: July 1, 2020
Lung cancer in East Asia is characterized by a high percentage of never-smokers, early onset and predominant EGFR mutations. To illuminate the molecular phenotype this demographically distinct disease, we performed deep comprehensive proteogenomic study on prospectively collected cohort Taiwan, representing stage, predominantly female, non-smoking lung adenocarcinoma. Integrated genomic, proteomic, phosphoproteomic analysis delineated attributes hallmarks tumor progression. Mutational signature revealed age- gender-related mutagenesis mechanisms, prevalence APOBEC mutational younger females over-representation environmental carcinogen-like signatures older females. A proteomics-informed classification distinguished clinical characteristics stage patients with Furthermore, integrated protein network cellular remodeling underpinning trajectories nominated candidate biomarkers for patient stratification therapeutic intervention. This multi-omic architecture may help develop strategies management never-smoker
Language: Английский
Citations
278
International Journal of Surgery, Journal Year: 2022, Volume and Issue: 107, P. 106936 - 106936
Published: Sept. 20, 2022
Postoperative progression and chemotherapy resistance is the major cause of treatment failure in patients with triple-negative breast cancer (TNBC). Currently, there a lack an ideal predictive model for drug sensitivity postoperative TNBC patients. Diverse programmed cell death (PCD) patterns play important role tumor progression, which has potential to be prognostic indicator after surgery.Twelve PCD (apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, entotic death, netotic parthanatos, lysosome-dependent autophagy-dependent alkaliptosis, oxeiptosis) were analyzed construction. Bulk transcriptome, single-cell genomics, clinical information collected from TCGA-BRCA, METABRIC, GSE58812, GSE21653, GSE176078, GSE75688, KM-plotter cohorts validate model.The machine learning algorithm established index (CDI) 12-gene signature. Validated five independent datasets, high CDI had worse prognosis surgery. Two molecular subtypes distinct vital biological processes identified by unsupervised clustering model. A nomogram performance was constructed incorporating features. Furthermore, associated immune checkpoint genes key microenvironment components integrated analysis bulk transcriptome. are resistant standard adjuvant regimens (docetaxel, oxaliplatin, etc.); however, they might sensitive palbociclib (an FDA-approved luminal cancer).Generally, we novel comprehensively analyzing diverse patterns, can accurately predict user-friendly website created facilitate application this prediction (https://tnbc.shinyapps.io/CDI_Model/).
Language: Английский
Citations
269
Genes, Journal Year: 2022, Volume and Issue: 13(5), P. 851 - 851
Published: May 10, 2022
Clear cell renal carcinoma (ccRCC) is the most prevalent subtype of carcinoma, which characterized by metabolic reprogramming. Cuproptosis, a novel form death, highly linked to mitochondrial metabolism and mediated protein lipoylation. However, clinical impacts cuproptosis-related genes (CRGs) in ccRCC largely remain unclear. In current study, we systematically evaluated genetic alterations ccRCC. Our results revealed that CDKN2A, DLAT, DLD, FDX1, GLS, PDHA1 PDHB exhibited differential expression between normal tissues (|log2(fold change)| > 2/3 p < 0.05). Utilizing an iterative sure independence screening (SIS) method, separately constructed prognostic signature CRGs for predicting overall survival (OS) progression-free (PFS) patients. The score yielded area under curve (AUC) 0.658 0.682 prediction 5-year OS PFS, respectively. Kaplan−Meier analysis OS, higher risk gene was significantly correlated with worse (HR = 2.72 (2.01−3.68), log-rank 1.76 × 10−7). Patients had shorter PFS 2.83 (2.08−3.85), 3.66 Two independent validation datasets (GSE40435 (N 101), GSE53757 72)) were collected meta-analysis, suggesting CDKN2A (log2(fold change) 1.46, 95%CI: 1.75−2.35) showed while DLAT −0.54, −0.93−−0.15) FDX1 −1.01, −1.61−−0.42) lowly expressed. also associated immune infiltration levels programmed death 1 (PD-1) (CDKN2A: r 0.24, 2.14 10−8; FDX1: −0.17, 1.37 10−4). conclusion, could serve as potential predictor patients may offer insights into cancer treatment.
Language: Английский
Citations
264