Cuproptosis-Associated lncRNA Establishes New Prognostic Profile and Predicts Immunotherapy Response in Clear Cell Renal Cell Carcinoma

Frontiers in Genetics, Journal Year: 2022, Volume and Issue: 13

Published: July 15, 2022

Background: Clear cell renal carcinoma (ccRCC) accounts for 80% of all kidney cancers and has a poor prognosis. Recent studies have shown that copper-dependent, regulated death differs from previously known mechanisms (apoptosis, ferroptosis, necroptosis) is dependent on mitochondrial respiration (Tsvetkov et al., Science, 2022, 375 (6586), 1254-1261). Studies also suggested targeting cuproptosis may be novel therapeutic strategy cancer therapy. In ccRCC, both lncRNA were critical, but the not fully understood. The aim our study was to construct prognostic profile based cuproptosis-associated lncRNAs predict prognosis ccRCC immune clear (ccRCC). Methods: We downloaded transcriptional clinical information Cancer Genome Atlas (TCGA). Co-expression network analysis, Cox regression method, least absolute shrinkage selection operator (LASSO) method used identify risk model. addition, predictive performance model validated recognized by an integrated approach. then constructed nomogram patients. Differences in biological function investigated GO, KEGG, immunoassay. Immunotherapy response measured using tumor mutational burden (TMB) dysfunction rejection (TIDE) scores. Results: panel 10 (HHLA3, H1-10-AS1, PICSAR, LINC02027, SNHG15, SNHG8, LINC00471, EIF1B-AS1, LINC02154, MINCR) prediction Kaplan-Meier ROC curves showed feature had acceptable validity TCGA training, test, complete groups. higher diagnostic efficiency compared other features. analysis Immune infiltration ssGSEA further confirmed features significantly associated with status Notably, superimposed effect patients high-risk group high TMB resulted shorter survival. TIDE scores poorer outcome checkpoint blockade these Conclusion: ten cuproptosis-related profiles help assess molecular improve treatment options, which can applied clinic.

Language: Английский

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Precise reconstruction of the TME using bulk RNA-seq and a machine learning algorithm trained on artificial transcriptomes

Cancer Cell, Journal Year: 2022, Volume and Issue: 40(8), P. 879 - 894.e16

Published: Aug. 1, 2022

Language: Английский

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RNA-seq data science: From raw data to effective interpretation

Frontiers in Genetics, Journal Year: 2023, Volume and Issue: 14

Published: March 13, 2023

RNA sequencing (RNA-seq) has become an exemplary technology in modern biology and clinical science. Its immense popularity is due large part to the continuous efforts of bioinformatics community develop accurate scalable computational tools analyze enormous amounts transcriptomic data that it produces. RNA-seq analysis enables genes their corresponding transcripts be probed for a variety purposes, such as detecting novel exons or whole transcripts, assessing expression alternative studying splicing structure. It can challenge, however, obtain meaningful biological signals from raw because scale well inherent limitations different technologies, amplification bias biases library preparation . The need overcome these technical challenges pushed rapid development tools, which have evolved diversified accordance with technological advancements, leading current myriad tools. These combined diverse skill sets biomedical researchers, help unlock full potential RNA-seq. purpose this review explain basic concepts define discipline-specific jargon.

Language: Английский

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Crosstalk between 5-methylcytosine and N6-methyladenosine machinery defines disease progression, therapeutic response and pharmacogenomic landscape in hepatocellular carcinoma

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Jan. 10, 2023

Accumulated evidence highlights the significance of crosstalk between epigenetic and epitranscriptomic mechanisms, notably 5-methylcytosine (5mC) N6-methyladenosine (m6A). Herein, we conducted a widespread analysis regarding 5mC m6A regulators in hepatocellular carcinoma (HCC).Pan-cancer genomic was presented at transcriptomic, genomic, epigenetic, other multi-omics levels. Hub were summarized to define an module eigengene (EME), which reflected both pre- post-transcriptional modifications.5mC interacted with one another multi-omic levels across pan-cancer, including HCC. The EME scoring system enabled greatly optimize risk stratification accurately predict HCC patients' clinical outcomes progression. Additionally, predicted responses mainstream therapies (TACE sorafenib) immunotherapy as well hyper-progression. In vitro, cooperatively weakened apoptosis facilitated proliferation, DNA damage repair, G2/M arrest, migration, invasion epithelial-to-mesenchymal transition (EMT) cells. remarkably linked potential extrinsic intrinsic immune escape high might contribute reduced copy number gain/loss frequency. Finally, determined therapeutic compounds druggable targets (TUBB1 P2RY4) for patients EME.Our findings suggest that may result from unique synergistic combination 5mC-epigenetic mechanism mixed m6A-epitranscriptomic mechanism, their defines response pharmacogenomic landscape.

Language: Английский

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A blueprint for tumor-infiltrating B cells across human cancers

Science, Journal Year: 2024, Volume and Issue: 384(6695)

Published: May 2, 2024

B lymphocytes are essential mediators of humoral immunity and play multiple roles in human cancer. To decode the functions tumor-infiltrating cells, we generated a cell blueprint encompassing single-cell transcriptome, cell-receptor repertoire, chromatin accessibility data across 20 different cancer types (477 samples, 269 patients). cells harbored extraordinary heterogeneity comprised 15 subsets, which could be grouped into two independent developmental paths (extrafollicular versus germinal center). Tumor extrafollicular pathway were linked with worse clinical outcomes resistance to immunotherapy. The dysfunctional program was associated glutamine-derived metabolites through epigenetic-metabolic cross-talk, promoted T cell-driven immunosuppressive program. These suggest an intratumor balance between germinal-center responses that possibly harnessed for cell-targeting

Language: Английский

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