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Background: Knee osteoarthritis (KOA) is a complex multifactorial disease, in which genetic factors account for 50% of the risk of osteoarthritis. This study investigated the association between ITLN1, XCL2 and DOT1L variants and KOA risk in the Han population. Methods: We applied Agena MassARRAY technology platform to genotype five single-nucleotide polymorphisms (SNPs) in 710 KOA patients and 709 controls. The correlation between ITLN1, XCL2 and DOT1L SNPs (rs2274908, rs4282797, rs4301615 and rs3815308) and KOA risk was calculated by logistic regression analysis, with odds ratio (OR) and 95% confidence intervals (CIs). Also, the relationship between genotypes at these different loci and clinical parameters (White blood cell, Eosinophil ratio, Neutrophil count, Eosinophil count, Monocyte ratio and Monocyte count) among patients and controls was analyzed. Results: In the overall results, rs2274908, rs4301615 and rs3815308 were correlated with KOA susceptibility. After gender stratification analysis, ITLN1 rs2274908 and XCL2 rs4301615 were related to an increased risk of KOA in males, and ITLN1 rs2274908 and DOT1L rs3815308 were related to an increased risk of KOA in females. After age stratification analysis, ITLN1 rs2274908 and XCL2 rs4301615 were correlated with an increased risk of KOA in people aged > 65 year old. After smoking stratification analysis and drinking stratification analysis, ITLN1 rs2274908, XCL2 rs4301615 and DOT1L rs3815308 were still associated with the risk of KOA. Conclusion: In short, ITLN1 rs2274908, XCL2 rs4301615 and DOT1L rs3815308 were related to KOA risk in the Han population, which was helpful to clarify the pathogenesis of these sites in KOA. [ABSTRACT FROM AUTHOR]

Simple Summary: Not all patients with advanced or metastatic non-small cell lung cancer (NSCLC) respond to pembrolizumab, even if their tumor expresses PD-L1. This is a monocentric study aimed at identifying potential predictive biomarkers for pembrolizumab first-line treatment. Tumor microenvironment was characterized by gene expression analysis in 46 tumor samples from 25 NSCLC patients with and 21 without durable clinical benefit. As expected, patients achieving clinical benefit had a greater infiltration of immune cells. In particular, CD8 T-cell and NK cell scores were strongly associated with durable benefit. Single immune cell markers such as XCL1/2 showed a high performance in predicting durable response to pembrolizumab with an AUC of 0.85. In the same series PD-L1 expression levels had an AUC equal to 0.61. Identified predictive biomarkers can improve patients' selection, thus optimizing treatment definition. Pembrolizumab has been approved as first-line treatment for advanced Non-small cell lung cancer (NSCLC) patients with tumors expressing PD-L1 and in the absence of other targetable alterations. However, not all patients that meet these criteria have a durable benefit. In this monocentric study, we aimed at refining the selection of patients based on the expression of immune genes. Forty-six consecutive advanced NSCLC patients treated with pembrolizumab in first-line setting were enrolled. The expression levels of 770 genes involved in the regulation of the immune system was analysed by the nanoString system. PD-L1 expression was evaluated by immunohistochemistry. Patients with durable clinical benefit had a greater infiltration of cytotoxic cells, exhausted CD8, B-cells, CD45, T-cells, CD8 T-cells and NK cells. Immune cell scores such as CD8 T-cell and NK cell were good predictors of durable response with an AUC of 0.82. Among the immune cell markers, XCL1/2 showed the better performance in predicting durable benefit to pembrolizumab, with an AUC of 0.85. Additionally, CD8A, CD8B and EOMES showed a high specificity (>0.86) in identifying patients with a good response to treatment. In the same series, PD-L1 expression levels had an AUC of 0.61. The characterization of tumor microenvironment, even with the use of single markers, can improve patients' selection for pembrolizumab treatment. [ABSTRACT FROM AUTHOR]