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Background: Genetic susceptibilities play a large role in the pathogenesis of lung cancer (LC). The polycomb repressive complex 2 (PRC2) is a conserved chromatin-associated complex that represses gene expression and is crucial for proper organismal development and gene expression patterns. Despite PRC2 dysregulation has been observed in various human cancers, the relationship between PRC2 genes variants and lung cancer risk remains largely unexplored.Methods: To investigate the association between single nucleotide polymorphisms (SNPs) in PRC2 genes and the risk of developing LC, we genotyped blood genomic DNA from 270 LC patients and 452 healthy individuals of Chinese Han ethnicity using the TaqMan™ genotyping technique.Results: We found that rs17171119T>G(adjusted odds ratio (OR) = 0.662, 95% CI: 0.467– 0.938, P < 0.05), rs10898459 T>C(adjusted OR = 0.615, 95% CI: 0.4– 0.947, P < 0.05), and rs1136258 C>T(adjusted OR = 0.273, 95% CI: 0.186– 0.401, P < 0.001) were significantly associated with a reduced risk of LC. Stratified analysis revealed a protective effect of rs17171119 in both male and female patients, specifically those with lung adenocarcinoma (LUAD). Additionally, rs1391221 showed a protective effect in both the LUAD and lung squamous cell carcinoma (LUSC) groups, while rs1136258 exhibited a protective effect in both females and males, as well as in both LUAD and LUSC groups. Furthermore, analysis of The Cancer Genome Atlas (TCGA) dataset revealed expression levels of EED and RBBP4 in both LUAD and LUSC.Conclusion: This study provides evidence that allelic variants in EZH2, EED, and RBBP4 may act as protective factors against LC development and could serve as genetic markers associated with susceptibility to LC. [ABSTRACT FROM AUTHOR]

Introduction: Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 80%– 85% of all cases of lung cancer. Huntingtin interacting protein-1 interacting protein (HIPPI) is a transcription regulator and plays an important role in apoptotic cell death. However, the role of HIPPI in NSCLC remains unclear. Methods: Immunohistochemistry (IHC) and qRT-PCR were performed for expression analysis. The roles of HIPPI were studied using cell counting kit-8 (CCK-8), colony formation, flow cytometry, wound healing, Transwell invasion assays and mouse xenograft model. Gene microarray analysis and bioinformatics analysis were used to identify differentially expressed genes after HIPPI silencing. Results: HIPPI is highly expressed in NSCLC tissues relative to adjacent normal tissues. Targeting HIPPI by RNA interference inhibits NSCLC cell proliferation in vitro and tumor growth in vivo. HIPPI silencing also attenuates cell migration and invasion and enhances cisplatin sensitivity in NSCLC cells. Mechanistic investigation suggests that HIPPI can positively regulate the expression of MCM2, MCM6 and MCM8, which are key regulators of DNA replication. Furthermore, consistent with HIPPI, MCM2, MCM6 and MCM8 are also upregulated in NSCLC tissues. Conclusion: Our study highlights the importance of HIPPI for tumor biology in NSCLC and suggests that HIPPI may be a potential therapeutic target for NSCLC treatment. [ABSTRACT FROM AUTHOR]

Introduction: Immune-based and antibody-drug conjugate therapies have shown promise in the treatment of patients with small cell lung cancer (SCLC). However, better predictive biomarkers are needed for selection of the appropriate SCLC patients for these advanced therapies and also for evaluation of the efficacy of these treatments. Objective: The aim of this study was to examine the expression of delta-like protein 3 (DLL3), cytotoxic T lymphocyte-associated protein 4 (CTLA-4), and mesothelin (MSTN) in patients with SCLC and compare them with those patients' clinical characteristics. Methods: Immunohistochemical analyses of DLL3, CTLA-4 and MSTN expression were performed in 38 samples from patients with SCLC. Results: We found that positive expression in patients of the biomarkers was as follows: for DLL3, 100% (38/38), for CTLA-4, 89.5% (36/38) and for MSTN 81.5% (31/38). The median survival time was 17.9 months in the DLL3 high expression group and 23 months in the DLL3 low expression group. Patients with a high expression of DLL3 showed a poorer prognosis than those with a low expression of DLL3 (HR=3.4; 95% CI, 1.34–8.6; p=0.01). Conclusion: The expression of DLL3, CTLA-4 and MSTN was not correlated with patients' age, sex, smoking status, stage, and tumor metastasis. The fact that there was a higher expression of DLL3, CTLA-4, and MSTN in SCLC suggested that these molecules could be used as predictive biomarkers for SCLC. [ABSTRACT FROM AUTHOR]