Lymphoma Heterogeneity Unraveled by Single-Cell Transcriptomics

Ysebaert, Loïc; Quillet‐Mary, Anne; Tosolini, Marie; Pont, Frédéric; Laurent, Camille; Fournié, Jean‐Jacques

doi:10.3389/fimmu.2021.597651

Cited by 10 publications

(4 citation statements)

References 76 publications

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“…Patients with DLBCL have different survival rates considering the heterogeneity of the diseases [ 29 ]. Current efforts have advanced in understanding the genome and transcriptome of DLBCL that distinguish subgroups of patients with poor prognosis after chemo-immunotherapy [ 30 – 33 ]. Autophagy-related gene expression profiles are believed to delineate two distinct groups of cases with high or low risks in terms of survival probability [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Prediction significance of autophagy-related genes in survival probability and drug resistance in diffuse large B-cell lymphoma

Xiong,

Wei,

Huang

et al. 2024

Aging

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Background/Aims: Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin lymphoma, has significant prognostic heterogeneity. This study aimed to generate a prognostic prediction model based on autophagy-related genes for DLBCL patients. Methods: Utilizing bioinformatics techniques, we analyzed the clinical information and transcriptome data of DLBCL patients from the Gene Expression Omnibus (GEO) database. Through unsupervised clustering, we identified new autophagy-related molecular subtypes and pinpointed differentially expressed genes (DEGs) between these subtypes. Based on these DEGs, a prognostic model was constructed using Cox and Lasso regression. The effectiveness, accuracy, and clinical utility of this prognostic model were assessed using numerous independent validation cohorts, survival analyses, receiver operating characteristic (ROC) curves, multivariate Cox regression analysis, nomograms, and calibration curves. Moreover, functional analysis, immune cell infiltration, and drug sensitivity analysis were performed. Results: DLBCL patients with different clinical characterizations (age, molecular subtypes, ECOG scores, and stages) showed different expression features of autophagy-related genes. The prediction model was constructed based on the eight autophagy-related genes (ADD3, IGFBP3, TPM1, LYZ, AFDN, DNAJC10, GLIS3, and CCDC102A). The prognostic nomogram for overall survival of DLBCL patients incorporated risk level, stage, ECOG scores, and molecular subtypes, showing excellent agreement between observed and predicted outcomes. Differences were noted in the proportions of immune cells (native B cells, Treg cells, CD8 + T cell, CD4 + memory activated T cells, gamma delta T cells, macrophages M1, and resting mast cells) between high-risk and low-risk groups. LYZ and ADD3 exhibited correlations with drug resistance to most chemotherapeutic drugs. Conclusions: This study established a novel prognostic assessment model based on the expression profile of autophagy-related genes and clinical characteristics of DLBCL patients, explored immune infiltration and predicted drug resistance, which may guide precise and individualized immunochemotherapy regimens.

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Section: Discussionmentioning

confidence: 99%

Prediction significance of autophagy-related genes in survival probability and drug resistance in diffuse large B-cell lymphoma

Xiong,

Wei,

Huang

et al. 2024

Aging

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“…That allows an unprecedented dissection of transcription within millions of individual cells. Both single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq) have exciting applications [65][66][67][68][69][70][71][72][73][74][75][76][77], for instance: (i) discovering and characterizing cell type in health and diseases, such as cancer [13,[78][79][80][81][82][83][84][85][86][87][88][89], with implications in immunology [90], immune-mediated diseases [91], immunotherapy [92][93][94][95][96][97][98][99][100] and drug resistance [101]; (ii) deciphering the roles of such specific cell types in health and disease [102], including mitochondrial heteroplasmy [33]; and (iii) analyzing cell emergence, development and plasticity in tissues and organisms. These studies are also applied to study plant biology [103,104].…”

Section: Functional Genomicsmentioning

confidence: 99%

Analyzing Modern Biomolecules: The Revolution of Nucleic-Acid Sequencing – Review

et al. 2021

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Recent developments have revolutionized the study of biomolecules. Among them are molecular markers, amplification and sequencing of nucleic acids. The latter is classified into three generations. The first allows to sequence small DNA fragments. The second one increases throughput, reducing turnaround and pricing, and is therefore more convenient to sequence full genomes and transcriptomes. The third generation is currently pushing technology to its limits, being able to sequence single molecules, without previous amplification, which was previously impossible. Besides, this represents a new revolution, allowing researchers to directly sequence RNA without previous retrotranscription. These technologies are having a significant impact on different areas, such as medicine, agronomy, ecology and biotechnology. Additionally, the study of biomolecules is revealing interesting evolutionary information. That includes deciphering what makes us human, including phenomena like non-coding RNA expansion. All this is redefining the concept of gene and transcript. Basic analyses and applications are now facilitated with new genome editing tools, such as CRISPR. All these developments, in general, and nucleic-acid sequencing, in particular, are opening a new exciting era of biomolecule analyses and applications, including personalized medicine, and diagnosis and prevention of diseases for humans and other animals.

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“…Several papers have recently been published on the status quo of single-cell technologies and on their applications in blood cancer research [ 20 , 21 , 22 , 24 , 25 , 28 , 74 , 75 , 76 ]. In this review, we specifically focus on pediatric leukemia with an aim to summarize how SCS studies shed light on the pathobiology of this disease group and discuss how different layers of single-cell omics approaches can expectedly support clinical decision making in the future.…”

Section: Introductionmentioning

confidence: 99%

Single-Cell Sequencing: Biological Insight and Potential Clinical Implications in Pediatric Leukemia

Alpár

Egyed

Bödör

et al. 2021

Cancers

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Single-cell sequencing (SCS) provides high-resolution insight into the genomic, epigenomic, and transcriptomic landscape of oncohematological malignancies including pediatric leukemia, the most common type of childhood cancer. Besides broadening our biological understanding of cellular heterogeneity, sub-clonal architecture, and regulatory network of tumor cell populations, SCS can offer clinically relevant, detailed characterization of distinct compartments affected by leukemia and identify therapeutically exploitable vulnerabilities. In this review, we provide an overview of SCS studies focused on the high-resolution genomic and transcriptomic scrutiny of pediatric leukemia. Our aim is to investigate and summarize how different layers of single-cell omics approaches can expectedly support clinical decision making in the future. Although the clinical management of pediatric leukemia underwent a spectacular improvement during the past decades, resistant disease is a major cause of therapy failure. Currently, only a small proportion of childhood leukemia patients benefit from genomics-driven therapy, as 15–20% of them meet the indication criteria of on-label targeted agents, and their overall response rate falls in a relatively wide range (40–85%). The in-depth scrutiny of various cell populations influencing the development, progression, and treatment resistance of different disease subtypes can potentially uncover a wider range of driver mechanisms for innovative therapeutic interventions.

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Lymphoma Heterogeneity Unraveled by Single-Cell Transcriptomics

Cited by 10 publications

References 76 publications

Prediction significance of autophagy-related genes in survival probability and drug resistance in diffuse large B-cell lymphoma

Prediction significance of autophagy-related genes in survival probability and drug resistance in diffuse large B-cell lymphoma

Analyzing Modern Biomolecules: The Revolution of Nucleic-Acid Sequencing – Review

Single-Cell Sequencing: Biological Insight and Potential Clinical Implications in Pediatric Leukemia

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