Germline genetic variants are associated with development of insulin-dependent diabetes in cancer patients treated with immune checkpoint inhibitors

Journal for ImmunoTherapy of Cancer, Год журнала: 2023, Номер 11(3), С. e006570 - e006570

Опубликована: Март 1, 2023

Background Immune checkpoint inhibitors (ICIs) have dramatically improved survival in patients with cancer but are often accompanied by severe immune-related adverse events (irAEs), which can sometimes be irreversible. Insulin-dependent diabetes is a rare, life-altering irAE. Our purpose was to determine whether recurrent somatic or germline mutations observed who develop insulin-dependent as an Methods We performed RNA and whole exome sequencing on tumors from 13 developed due ICI exposure (ICI-induced mellitus, ICI-DM) compared control did not diabetes. Results In ICI-DM patients, we find differences expression of conventional type 1 autoantigens, observe significant overexpression ORM1, PLG, G6PC, all been implicated related pancreas islet cell function. Interestingly, missense mutation NLRC5 9 the that treated same drugs for cancers. Germline DNA sequenced; were germline. The prevalence variants significantly greater than general population (p=5.98×10 −6 ). Although development diabetes, found public databases suggesting different mechanism immunotherapy-treated cancer. Conclusions Validation potential predictive biomarker warranted, it might improve patient selection treatment regimens. Furthermore, this genetic alteration suggests mechanisms destruction setting inhibitor therapy.

Язык: Английский

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Identification of crucial extracellular genes as potential biomarkers in newly diagnosed Type 1 diabetes via integrated bioinformatics analysis

PeerJ, Год журнала: 2025, Номер 13, С. e18660 - e18660

Опубликована: Янв. 9, 2025

In this study, we aimed to study the role of extracellular proteins as biomarkers associated with newly diagnosed Type 1 diabetes (NT1D) diagnosis and prognosis. We retrieved analyzed GSE55098 microarray dataset from Gene Expression Omnibus (GEO) database. Using R software, screened out protein-differentially expressed genes (EP-DEGs) through several protein-related databases. Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) analyses were applied describe function these EP-DEGs. used STRING database construct interaction proteins, Cytoscape software visualize protein-protein (PPI) networks, its plugin CytoHubba identify crucial between PPI networks. Finally, comparative toxicogenomics (CTD) evaluate connection NT1D potential validated our conclusions another (GSE33440) some clinical samples. identified 422 DEGs 122 EP-DEGs a that includes (12) patients compared (10) healthy people. Protein digestion absorption, toll-like receptor signaling, T cell signaling most meaningful pathways defined by KEGG enrichment analyses. recognized nine important genes: The key genes, particularly

Язык: Английский

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Osmosensor TMEM63B facilitates insulin secretion in pancreatic β-cells

Science China Life Sciences, Год журнала: 2025, Номер unknown

Опубликована: Фев. 20, 2025

Язык: Английский

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A new perspective on the autophagic and non-autophagic functions of the GABARAP protein family: a potential therapeutic target for human diseases

Molecular and Cellular Biochemistry, Год журнала: 2023, Номер 479(6), С. 1415 - 1441

Опубликована: Июль 13, 2023

Язык: Английский

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Riemannian manifold-based geometric clustering of continuous glucose monitoring to improve personalized diabetes management

Computers in Biology and Medicine, Год журнала: 2024, Номер 183, С. 109255 - 109255

Опубликована: Окт. 16, 2024

Язык: Английский

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A new machine learning based computational framework identifies therapeutic targets and unveils influential genes in pancreatic islet cells

Gene, Год журнала: 2022, Номер 853, С. 147038 - 147038

Опубликована: Ноя. 28, 2022

Язык: Английский

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In silico identification and functional prediction of differentially expressed genes in South Asian populations associated with type 2 diabetes

PLoS ONE, Год журнала: 2023, Номер 18(12), С. e0294399 - e0294399

Опубликована: Дек. 14, 2023

Type 2 diabetes (T2D) is one of the major metabolic disorders in humans caused by hyperglycemia and insulin resistance syndrome. Although significant genetic effects on T2D pathogenesis are experimentally proved, molecular mechanism South Asian Populations (SAPs) still limited. Hence, current research analyzed two Gene Expression Omnibus (GEO) 17 Genome-Wide Association Studies (GWAS) datasets associated with SAP to identify DEGs (differentially expressed genes). The identified were further explore following a series bioinformatics approaches. Following PPI (Protein-Protein Interaction), 867 potential nine hub genes that might play roles pathogenesis. Interestingly, CTNNB1 RUNX2 found be unique for SAPs. Then, GO (Gene Ontology) showed biological, molecular, cellular functions DEGs. target also interacted different pathways In fact, 118 (including HNF1A TCF7L2 genes) directly Indeed, eight key miRNAs among 2582 significantly genes. Even 64 downregulated 367 FDA-approved drugs. 11 wide range (9-43) drug specificity. may guide elucidate Therefore, integrating findings candidate drug-mediated downregulation marker genes, future drugs or treatments could developed treat

Язык: Английский

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CCDC158: A novel regulator in renal proximal tubular endocytosis unveiled through exome sequencing and interactome analysis

Journal of Cellular Physiology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 25, 2024

Abstract Renal proximal tubular reabsorption of proteins and polypeptides is tightly regulated by a concerted action the multi‐ligand receptors with subsequent processing from clathrin‐coated pits to early/recycling late endosomes towards lysosomes. We performed whole exome‐sequencing in male patient consanguineous family, who presented low‐ intermediate molecular weight proteinuria, nephrocalcinosis oligospermia. identified new potential player endocytosis, coiled‐coil domain containing 158 (CCDC158). The variant CCDC158 segregated phenotype was also detected female sibling similar clinical kidney phenotype. demonstrated expression this protein tubules modeled its structure silico . hypothesized that played role endocytosis interacting other regulators, used mass spectrometry identify interactors. receptor‐mediated further confirmed transferrin GST‐RAP trafficking analyses patient‐derived epithelial cells. Finally, as known be expressed testis, presence oligospermia substantiated pathogenic missense observed In study, we provide data demonstrate most likely interaction endocytosis‐related strongly correlate dysfunction patients. However, more studies are needed fully unravel mechanism(s) which involved.

Язык: Английский

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Exploring Computational Data Amplification and Imputation for the Discovery of Type 1 Diabetes (T1D) Biomarkers from Limited Human Datasets

Biomolecules, Год журнала: 2022, Номер 12(10), С. 1444 - 1444

Опубликована: Окт. 9, 2022

Background: Type 1 diabetes (T1D) is a devastating disease with serious health complications. Early T1D biomarkers that could enable timely detection and prevention before the onset of clinical symptoms are paramount but currently unavailable. Despite their promise, omics approaches have so far failed to deliver such biomarkers, likely due fragmented nature information obtained through single approach. We recently demonstrated utility parallel multi-omics for identification biomarker signatures. Our studies also identified challenges. Methods: Here, we evaluated novel computational approach data imputation amplification as one way overcome challenges associated relatively small number subjects in these studies. Results: Using proprietary algorithms, amplified our quadra-omics (proteomics, metabolomics, lipidomics, transcriptomics) dataset from nine thousand-fold analyzed using Ingenuity Pathway Analysis (IPA) software assess change its analytical capabilities prediction power datasets compared original. These showed ability identify an increased T1D-relevant pathways computationally datasets, especially, at ratios close “golden ratio” 38.2%:61.8%. Specifically, Canonical Diseases Functions modules higher numbers inflammatory functions relevant autoimmune T1D, including ones not original data. The Biomarker Prediction module predicted several unique candidates direct links pathogenesis. Conclusions: preliminary findings indicate large-scale useful facilitating discovery candidate integrated signatures or other diseases by increasing predictive range existing mining tools, especially when size input inherently limited.

Язык: Английский

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Roles of ANP32 proteins in cell biology and viral replication

Animal Diseases, Год журнала: 2022, Номер 2(1)

Опубликована: Окт. 11, 2022

Abstract The acidic leucine-rich nuclear phosphoprotein 32 kDa (ANP32) family consists of evolutionarily conserved proteins 220–291 amino acids characterized by an N-terminal repeat domain (LRR) and a C-terminal low-complexity region (LCAR). ANP32 regulate variety physiological functions, including chromatin remodeling, apoptosis nervous system development. Abnormal expression is closely related to tumorigenesis. In recent years, the role in viral infections has received considerable attention due their activity supporting influenza virus replication restriction cross-species transmission. Moreover, are HIV nonsegmented negative-strand RNA viruses (NNSVs). this review, general functions proteins, as well roles replication, summarized detail.

Язык: Английский

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