Pyroptosis and Inflammasome-Related Genes-NLRP3, NLRC4 and NLRP7 Polymorphisms Were Associated with Risk of Lung Cancer

Pharmacogenomics and Personalized Medicine, Год журнала: 2023, Номер Volume 16, С. 795 - 804

Опубликована: Авг. 1, 2023

Cancer development and tumor immune microenvironment remodeling are closely linked to pyroptosis inflammasome activation. However, little information is available in single nucleotide polymorphisms (SNPs) inflammasome-related genes patients with lung cancer. This study aims evaluate the associations between pyroptosis-related gene (NLRP3, NLRC4, NLRP7) risk of cancer.The MassARRAY platform was used genotype six SNPs NLRP3, NLRP7 660 cancer cases controls.Individuals rs35829419-A, rs385076-C, rs775882-T alleles exhibited a higher (p < 0.01), while rs212704-T appears protective = 0.006). The rs35829419-AA, rs385076-TC/CC, rs775882-CT/TT genotypes were associated various degrees elevated (p<0.02), whereas rs212704-TT reduced disease (p=0.014). Genetic models analysis showed that rs35829419, rs385076, rs775882 an increased cancer, rs212704 related all three 0.05). four remained significant smoker nonsmoker subgroups rs35829419 correlated adenocarcinoma small cell only for squamous carcinoma. rs385076 pathological types 0.01).Besides providing candidate markers identification high-risk populations early prevention disease, our research also provided new insight into anti-tumor strategies targeting inflammasomes pyroptosis.

Язык: Английский

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Exosomal lncCRLA is predictive for the evolvement and development of lung adenocarcinoma

Cancer Letters, Год журнала: 2023, Номер 582, С. 216588 - 216588

Опубликована: Дек. 12, 2023

Lung adenocarcinoma, the most common histological subtype of non-small cell lung cancer, exhibits heterogeneity that enables adaptability, limits therapeutic success, and remains incompletely understood. Our team uncovers lncRNA related to chemotherapy resistance in adenocarcinoma (lncCRLA) is preferentially expressed cells with mesenchymal phenotype. lncCRLA can not enhance due its binding RIPK1 exosomes, which released into intercellular media transferred by exosomes from mesenchymal-like epithelial-like cells. However, plasmatic corresponding tissue functions as a preferred biomarker reflect response disease progression adenocarcinoma. Through single-cell sequencing, RNA-Mutect technique spatial transcriptomics, handful hybrid EMT elevated are characterized origin indiscriminated in-depth sequencing. Plasmatic properly predictive for preinvasive lesion would evolve invasive lesion. That notion confirmed brand-new transgenic mouse model tracked Cre Dre system. Dasatinib potential hinder spontaneous Together, defined circulating predict occurrence evolvement light early detection

Язык: Английский

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Comprehensive functional interrogation of susceptibility loci in GWASs identified KIAA0391 as a novel oncogenic driver via regulating pyroptosis in NSCLC

Cancer Letters, Год журнала: 2024, Номер 585, С. 216646 - 216646

Опубликована: Янв. 21, 2024

Язык: Английский

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MTF1 genetic variants are associated with lung cancer risk in the Chinese Han population

BMC Cancer, Год журнала: 2024, Номер 24(1)

Опубликована: Июнь 28, 2024

Metal-regulatory transcription factor 1 (MTF1), a conserved metal-binding in eukaryotes, regulates the proliferation of cancer cells by activating downstream target genes and then participates formation progression tumors, including lung (LC). The expression level MTF1 is down-regulated LC, high associated with good prognosis LC. However, association between polymorphism LC risk has not been explored.

Язык: Английский

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Systematic identification of pathogenic variants of non-small cell lung cancer in the promoters of DNA-damage repair genes

EBioMedicine, Год журнала: 2024, Номер 110, С. 105480 - 105480

Опубликована: Дек. 1, 2024

SummaryBackgroundDeficiency in DNA-damage repair (DDR) genes, often due to disruptive coding variants, is linked higher cancer risk. Our previous study has revealed the association between rare loss-of-function variants DDR genes and risk of lung cancer. However, it still challenging predisposing role regulatory these genes.MethodsBased on whole-genome sequencing data from 2984 patients with non-small cell (NSCLC) 3020 controls, we performed massively parallel reporter assays 1818 located promoters genes. Pathway- or gene-level burden analyses were using Firth's logistic regression generalized linear model.FindingsWe identified 750 functional (frVars) that showed allelic differences transcriptional activity within promoter regions Interestingly, frVars was significantly elevated cases (odds ratio [OR] = 1.17, p 0.026), whereas prioritized solely based bioinformatics annotation comparable controls (OR 1.04, 0.549). Among frVars, 297 down-regulated (dr-frVars) 453 up-regulated (ur-frVars); especially, dr-frVars 1.30, 0.008) rather than ur-frVars 1.06, 0.495) associated NSCLC. Individuals NSCLC carried more Fanconi anemia, homologous recombination, nucleotide excision pathways. In addition, seven (i.e., BRCA2, GTF2H1, DDB2, BLM, ALKBH2, APEX1, RAD51B) susceptibility.InterpretationOur findings indicate addition protein-truncating can be pathogenic contribute susceptibility.FundingNational Natural Science Foundation China, Youth Jiangsu Province, Research Unit Prospective Cohort Cardiovascular Diseases Cancer Chinese Academy Medical Sciences, Province.

Язык: Английский

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