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

Mingxing An,

Congcong Chen, Jun Xiang

et al.

EBioMedicine, Journal Year: 2024, Volume and Issue: 110, P. 105480 - 105480

Published: Dec. 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.

Language: Английский

Professionalism vs. engagement: quality of SSc information on WeChat DOI Creative Commons
Lei Wang, Xiong Yue,

Tingting Wu

et al.

Frontiers in Public Health, Journal Year: 2025, Volume and Issue: 13

Published: May 14, 2025

Background Systemic sclerosis (SSc) is a rare autoimmune disease, and WeChat major source of health information in China. This study assesses the quality SSc on to understand its impact public knowledge engagement. Methods A total 375 articles from 9 accounts were systematically analyzed using DISCERN Global Quality Scale (GQS) tools. Article was evaluated based credibility, content accuracy, user engagement, including metrics such as views, likes, comments. Results Individual authors posted 50% articles, while non-profit organizations 21%, with non-profits providing higher content. Disease dominated (52.8%), yet readers showed interest policy interpretation rehabilitation. The average GQS scores 28.96 1.62, indicating low across articles. Conclusion While facilitates dissemination, overall lacking. Enhancing professionalism interactivity platforms like could better meet needs patients for reliable information.

Language: Английский

Citations

0
NLRP7 participates in the human subcortical maternal complex and its variants cause female infertility characterized by early embryo arrest DOI
Jian Han, Nana Zhang, Qiqi Cao

et al.

Journal of Molecular Medicine, Journal Year: 2023, Volume and Issue: 101(6), P. 717 - 729

Published: May 6, 2023

Language: Английский

Citations

9
Integrative splicing-quantitative-trait-locus analysis reveals risk loci for non-small-cell lung cancer DOI Creative Commons
Yuzhuo Wang, Yue Ding,

Su Liu

et al.

The American Journal of Human Genetics, Journal Year: 2023, Volume and Issue: 110(9), P. 1574 - 1589

Published: Aug. 9, 2023

Language: Английский

Citations

9
Single nucleotide variants in lung cancer DOI Creative Commons
Xiaoling Tian, Zhe Liu

Chinese Medical Journal - Pulmonary and Critical Care Medicine, Journal Year: 2024, Volume and Issue: 2(2), P. 88 - 94

Published: June 1, 2024

Germline genetic variants, including single-nucleotide variants (SNVs) and copy number (CNVs), account for interpatient heterogeneity. In the past several decades, genome-wide association studies (GWAS) have identified multiple lung cancer-associated SNVs in Caucasian Chinese populations. These either reside within coding regions change structure function of cancer-related proteins or non-coding alter expression level proteins. The can be used not only cancer risk assessment prevention but also development new therapies. this review, we discuss to date, their contributions tumorigenesis prognosis, potential use predicting prognosis implementing therapeutic strategies.

Language: Английский

Citations

3
SEAD reference panel with 22,134 haplotypes boosts rare variant imputation and genome-wide association analysis in Asian populations DOI Creative Commons
Mengyuan Yang,

Jia-Dong Zhong,

Xin Li

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Dec. 30, 2024

Limited whole genome sequencing (WGS) studies in Asian populations result a lack of representative reference panels, thus hindering the discovery ancestry-specific variants. Here, we present South and East Database (SEAD) panel ( https://imputationserver.westlake.edu.cn/ ), which integrates WGS data for 11,067 individuals from various sources across 17 countries. The SEAD panel, comprising 22,134 haplotypes 88,294,957 variants, demonstrates improved imputation accuracy compared to 1000 Genomes Project, TOPMed, ChinaMAP with higher proportion well-imputed rare For populations, shows concordance comparable ChinaMAP, but outperforming TOPMed. Additionally, apply conduct genome-wide association study total hip (Hip) femoral neck (FN) bone mineral density (BMD) traits 5369 genotyped Chinese samples. single-variant test suggests that variants near SNTG1 are associated Hip BMD (rs60103302, MAF = 0.0092, P 1.67 × 10-7), variant-set analysis further supports (Pslide_window 9.08 10-9, Pgene_centric 5.27 10-8). This was not reported previously can only be detected by using panels. Preliminary vitro experiments one identified provide evidence it upregulates expression, could turn inhibit proliferation differentiation preosteoblasts.

Language: Английский

Citations

3
Paternal genomic resources from the YanHuang cohort suggested a Weakly-Differentiated Multi-source Admixture model for the formation of Han’s founding ancestral lineages DOI Creative Commons

Zhiyong Wang,

Mengge Wang, Kaijun Liu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 13, 2023

Abstract The large-scale human genome revolution and rapidly advanced statistical innovation have updated our understanding of the fine-scale complex genetic structure, entire landscape diversity evolutionary trajectories spatiotemporally different ancients ethnolinguistically diverse modern populations. Recent ancient DNA research provided a detailed admixture picture Europeans but limited insights into East Asians as few available genomes. Y-chromosome variations in male-specific regions, served molecular archaeological tool, unique features that can be utilized to reconstruct origin subsequent interaction Asian paternal lineages. We launched YanHuang cohort using designed highest-resolution capture sequencing panel explore trajectory Han Chinese, one largest ethnic groups world. reported uniparental genomic resources observed multiple founding lineages dominant western Eurasian, Siberian participating formation gene pool Chinese. identified structure correlated with patterns population geographical mountain barriers (Qinling-Huaihe line Nanling Mountains), suggesting isolation-enhanced admixture-introduced differentiation enhanced complexity Chinese diversity. strong direct correlation between frequency proportion subsistence-related ancestry sources related pastoralists, Holocene Mongolian Plateau people Asians, reflecting migration events contributed finally novel most plausible admixture-by-admixture model, Weakly-Differentiated Multi-Source Admixture major mechanism illuminate pattern interactions ancestral Generally, we presented resource from cohort, portrayed model herders, hunter-gatherers farmers who participated

Language: Английский

Citations

8
The design and implementation of natural population cohort study Biobank: A multiple-center project cooperation with medical consortia in Southwest China DOI Creative Commons
Ping Fan, Shu Zhang, Weiya Wang

et al.

Frontiers in Public Health, Journal Year: 2022, Volume and Issue: 10

Published: Dec. 1, 2022

Objective The West China Hospital of Sichuan University collaborated with regional medical consortia in Province to launch a natural population cohort study (NPCS) investigate the health status residents and collect public data southwest China. Methods Up 80,000 participants will be enrolled by NPCS from 11 over five years. Individuals are invited visit one participating fill out questionnaires, receive free exam, donate biospecimens upon enrolment. All facilities adhered standard operating procedures for collecting processing ensure uniformity (serum, lithium heparinized plasma, ethylene diamine tetraacetie acid buffy coat). Electronic Data Capture System, Picture Archiving Communication Laboratory Information Management Biospecimen Quality Control Biobank used sort classify clinical indices, imaging data, laboratory parameters, pre-analytical variables, biospecimen information, respectively. quality assurance control biobank “DAIDS Guidelines Good Clinical Practice Standards”. This project integrate high-dimensional multi-omics questionnaire environmental risk factors. Results An estimated 2,240,000 aliquots sample stored end study. These samples linked comprehensively collected parameters. Big analysis can implemented create predictive algorithms, explore pathogenesis mechanisms, uncover potential biomarkers, provide information on health. Conclusions an integrative approach research factors major chronic or endemic diseases key scientific evidence support formulation management policies

Language: Английский

Citations

12
Integrating genomics and proteomics data to identify candidate plasma biomarkers for lung cancer risk among European descendants DOI
Yaohua Yang, Shuai Xu, Guochong Jia

et al.

British Journal of Cancer, Journal Year: 2023, Volume and Issue: 129(9), P. 1510 - 1515

Published: Sept. 7, 2023

Language: Английский

Citations

7
Current status of molecular diagnostics for lung cancer DOI Creative Commons
Evgeny N. Imyanitov, Elena V. Preobrazhenskaya, С. В. Орлов

et al.

Exploration of Targeted Anti-tumor Therapy, Journal Year: 2024, Volume and Issue: 5(3), P. 742 - 765

Published: June 27, 2024

The management of lung cancer (LC) requires the analysis a diverse spectrum molecular targets, including kinase activating mutations in EGFR, ERBB2 (HER2), BRAF and MET oncogenes, KRAS G12C substitutions, ALK, ROS1, RET NTRK1-3 gene fusions. Administration immune checkpoint inhibitors (ICIs) is based on immunohistochemical (IHC) PD-L1 expression determination tumor mutation burden (TMB). Clinical characteristics patients, particularly age, gender smoking history, significantly influence probability finding above targets: for example, LC young patients characterized by high frequency rearrangements, while heavy smokers often have and/or TMB. Proper selection first-line therapy influences overall treatment outcomes, therefore, majority these tests need to be completed within no more than 10 working days. Activating events MAPK signaling pathway are mutually exclusive, hence, fast single-gene testing remains an option some laboratories. RNA next-generation sequencing (NGS) capable detecting entire repertoire druggable alterations, therefore it gradually becoming dominating technology diagnosis.

Language: Английский

Citations

2
BRCA2 mutation in advanced lung squamous cell carcinoma treated with Olaparib and a PD-1 inhibitor: a case report DOI Creative Commons
Zhujun Chen, Kang Wang,

Lintao Zhao

et al.

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: May 16, 2023

Background Mutations in the human breast cancer susceptibility gene 2 (breast 2, BRCA2) increase risk of breast, ovarian and other cancers. Olaparib, an oral poly[adenosine diphosphate (ADP)–ribose] polymerase (PARP) inhibitor, is usually prescribed to treat BRCA mutated tumors, especially Programmed cell death-1 (PD-1) inhibitors have revolutionized treatment lung many cancers by destroying interaction between receptors with ligands tumor-immune microenvironment enabling T cells recognize attack cells. Case description In our study, we report a patient advanced BRCA2 squamous carcinoma who received platinum-based chemotherapy combined paclitaxel. Seven months later, disease progressed. mutations were detected peripheral blood next-generation sequencing. After Olaparib Cindilimab, was partial remission progression-free survival (PFS) lasted for 6 months, but developed immune renal damage. Conclusions This study adds clinical data mutant non-small demonstrating that has good response PARP inhibitors. It also serves as reminder there may still be some negative effects from targeted superimposed immunotherapy.

Language: Английский

Citations

6