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Multi-Omics and Single-Cell Mendelian Randomization Reveal a Potential Role of VNN2 in Lung Adenocarcinoma in Resting Natural Killer Cells

World J Oncol. 2026 Mar 5;17(2):247-255. doi: 10.14740/wjon2689. eCollection 2026 Apr.

ABSTRACT

BACKGROUND: We aimed to evaluate the potential association between genetically predicted vanin-2 (VNN2) expression and lung adenocarcinoma (LUAD) risk, and to explore the immune cell subtype that may underlie this relationship.

METHODS: We integrated whole-blood expression quantitative trait loci (eQTL) data from eQTLGen, plasma protein quantitative trait loci (pQTL) data from deCODE, and LUAD genome-wide association study (GWAS) data from European-ancestry cohorts, together with differential expression analysis using GEPIA2, to identify candidate genes for subsequent single-cell eQTL (sc-eQTL) Mendelian randomization (MR) analysis. For the sc-eQTL analysis, VNN2-associated eQTLs from 14 immune cell types profiled in the OneK1K single-cell eQTL resource were tested for associations with LUAD risk.

RESULTS: Bulk-level MR analysis showed that genetically predicted increases in VNN2 expression and protein levels were significantly associated with a reduced risk of LUAD (eQTL-MR: odds ratio (OR) = 0.964, 95% confidence interval (95% CI), 0.934-0.995; P = 0.024; pQTL-MR: OR = 0.946, 95% CI, 0.921-0.970; P = 2.87 × 10-5). Transcriptomic analyses confirmed significant downregulation of VNN2 in LUAD tumors compared with normal lung tissues. sc-eQTL MR identified the strongest association in resting natural killer (rNK) cells (OR = 0.896, 95% CI, 0.829-0.967; P = 0.005).

CONCLUSIONS: Multi-omics and sc-eQTL MR analyses indicated that genetically predicted increases in VNN2 expression were associated with a reduced risk of LUAD, with the most pronounced effect observed in rNK cells. These findings suggest a potential cell type-specific role of VNN2 in LUAD susceptibility and warrant further studies to validate its biological relevance and clinical implications.

PMID:41822323 | PMC:PMC12978397 | DOI:10.14740/wjon2689

Breast Cancer Screening Knowledge and Sentiments in Singaporean Women: Mixed Methods Study Using Topic Modeling, Sentiment Analysis, and Structured Questionnaire Data

Background: Mammography screening uptake in Singapore remains below 40% despite campaigns and subsidies. Natural language processing (NLP) can extract nuanced attitudes from free text that fixed response options miss, revealing latent factors influencing breast cancer (BC) screening behavior. Objective: This study characterized women’s attitudes toward mammography using mixed methods data, examined associations between BC awareness and screening willingness, and identified barriers and facilitators through NLP of free-text responses. Methods: We conducted a cross-sectional study within the multicenter cohort in Singapore (October 2021-December 2023). In total, 4169 women aged 35‐59 years (median 48, IQR 43‐54) were recruited via convenience sampling (3 hospitals and 2 polyclinics). Participants completed online structured questionnaires on demographics and screening history, then a BC education quiz with feedback. Participants answering >80% correctly were classified as “BC-aware.” Posteducation, participants reported screening willingness (motivated or neutral) with optional free-text explanations. Logistic regression models (adjusted for study site, age, ethnicity, marital status, housing, and education) examined the associations with willingness. For 3819 English-language respondents, biterm topic modeling identified themes and sentiment analysis quantified emotional tone. Statistical significance: =.05. Results: Overall, 79% (3287/4169) were BC-aware, and 94% (3908/4169) reported increased motivation posteducation. BC-aware women had higher screening motivation than BC-unaware women (adjusted odds ratio [aOR] 2.88, 95% CI 2.19‐3.80;
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