Image_1_Immune infiltration landscape on prognosis and therapeutic response and relevant epigenetic and transcriptomic mechanisms in lung adenocarcinoma.tif

ObjectiveLung adenocarcinoma (LUAD) is the most prevalent lung cancer subtype, but its immune infiltration features are not comprehensively understood. To address the issue, the present study was initiated to describe the immune infiltrations across LUAD from cellular compositional, functional, and mechanism perspectives.MethodsWe adopted five LUAD datasets (GSE32863, GSE43458, GSE75037, TCGA-LUAD, and GSE72094). Differentially expressed genes between LUAD and controls were selected for co-expression network analysis. Risky immune cell types were determined for classifying LUAD patients as diverse subtypes, followed by a comparison of antitumor immunity and therapeutic response between subtypes. Then, LUAD- and subtype-related key module genes affected by DNA methylation were determined for quantifying a scoring scheme. EXO1 was chosen for functional analysis via in vitro assays.ResultsTwo immune cell infiltration-based subtypes (C1 and C2) were established across LUAD, with poorer prognostic outcomes and lower infiltration of immune cell types in C1. Additionally, C1 presented higher responses to immune checkpoint blockade and targeted agents (JNK inhibitor VIII, BI-D1870, RO-3306, etc.). The scoring system (comprising GAPDH, EXO1, FYN, CFTR, and KLF4) possessed higher accuracy in estimating patients’ prognostic outcomes. EXO1 upregulation contributed to the growth, migration, and invasion of LUAD cells. In addition, EXO1 facilitated PD-L1 and sPD-L1 expression in LUAD cells.ConclusionAltogether, our findings offer a comprehensive understanding of the immune infiltration landscape on prognosis and therapeutic response of LUAD as well as unveil potential epigenetic and transcriptomic mechanisms, which might assist personalized treatment.</p

Table_1_Immune infiltration landscape on prognosis and therapeutic response and relevant epigenetic and transcriptomic mechanisms in lung adenocarcinoma.xlsx

ObjectiveLung adenocarcinoma (LUAD) is the most prevalent lung cancer subtype, but its immune infiltration features are not comprehensively understood. To address the issue, the present study was initiated to describe the immune infiltrations across LUAD from cellular compositional, functional, and mechanism perspectives.MethodsWe adopted five LUAD datasets (GSE32863, GSE43458, GSE75037, TCGA-LUAD, and GSE72094). Differentially expressed genes between LUAD and controls were selected for co-expression network analysis. Risky immune cell types were determined for classifying LUAD patients as diverse subtypes, followed by a comparison of antitumor immunity and therapeutic response between subtypes. Then, LUAD- and subtype-related key module genes affected by DNA methylation were determined for quantifying a scoring scheme. EXO1 was chosen for functional analysis via in vitro assays.ResultsTwo immune cell infiltration-based subtypes (C1 and C2) were established across LUAD, with poorer prognostic outcomes and lower infiltration of immune cell types in C1. Additionally, C1 presented higher responses to immune checkpoint blockade and targeted agents (JNK inhibitor VIII, BI-D1870, RO-3306, etc.). The scoring system (comprising GAPDH, EXO1, FYN, CFTR, and KLF4) possessed higher accuracy in estimating patients’ prognostic outcomes. EXO1 upregulation contributed to the growth, migration, and invasion of LUAD cells. In addition, EXO1 facilitated PD-L1 and sPD-L1 expression in LUAD cells.ConclusionAltogether, our findings offer a comprehensive understanding of the immune infiltration landscape on prognosis and therapeutic response of LUAD as well as unveil potential epigenetic and transcriptomic mechanisms, which might assist personalized treatment.</p

Table_2_Immune infiltration landscape on prognosis and therapeutic response and relevant epigenetic and transcriptomic mechanisms in lung adenocarcinoma.xlsx

ObjectiveLung adenocarcinoma (LUAD) is the most prevalent lung cancer subtype, but its immune infiltration features are not comprehensively understood. To address the issue, the present study was initiated to describe the immune infiltrations across LUAD from cellular compositional, functional, and mechanism perspectives.MethodsWe adopted five LUAD datasets (GSE32863, GSE43458, GSE75037, TCGA-LUAD, and GSE72094). Differentially expressed genes between LUAD and controls were selected for co-expression network analysis. Risky immune cell types were determined for classifying LUAD patients as diverse subtypes, followed by a comparison of antitumor immunity and therapeutic response between subtypes. Then, LUAD- and subtype-related key module genes affected by DNA methylation were determined for quantifying a scoring scheme. EXO1 was chosen for functional analysis via in vitro assays.ResultsTwo immune cell infiltration-based subtypes (C1 and C2) were established across LUAD, with poorer prognostic outcomes and lower infiltration of immune cell types in C1. Additionally, C1 presented higher responses to immune checkpoint blockade and targeted agents (JNK inhibitor VIII, BI-D1870, RO-3306, etc.). The scoring system (comprising GAPDH, EXO1, FYN, CFTR, and KLF4) possessed higher accuracy in estimating patients’ prognostic outcomes. EXO1 upregulation contributed to the growth, migration, and invasion of LUAD cells. In addition, EXO1 facilitated PD-L1 and sPD-L1 expression in LUAD cells.ConclusionAltogether, our findings offer a comprehensive understanding of the immune infiltration landscape on prognosis and therapeutic response of LUAD as well as unveil potential epigenetic and transcriptomic mechanisms, which might assist personalized treatment.</p

Association between Common Variants near <em>LBX1</em> and Adolescent Idiopathic Scoliosis Replicated in the Chinese Han Population

<div><h3>Background</h3><p>Adolescent idiopathic scoliosis (AIS) is one of the most common spinal deformities found in adolescent populations. Recently, a genome-wide association study (GWAS) in a Japanese population indicated that three single nucleotide polymorphisms (SNPs), rs11190870, rs625039 and rs11598564, all located near the <em>LBX1</em> gene, may be associated with AIS susceptibility <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053234#pone.0053234-Takahashi1">[1]</a>. This study suggests a novel AIS predisposition candidate gene and supports the hypothesis that somatosensory functional disorders could contribute to the pathogenesis of AIS. These findings warrant replication in other populations.</p> <h3>Methodology/Principal Findings</h3><p>First, we conducted a case-control study consisting of 953 Chinese Han individuals from southern China (513 patients and 440 healthy controls), and the three SNPs were all found to be associated with AIS predisposition. The ORs were observed as 1.49 (95% CI 1.23–1.80, <em>P</em> = 5.09E-5), 1.70 (95% CI 1.42–2.04, <em>P</em> = 1.17E-8) and 1.52 (95% CI 1.27–1.83, <em>P</em> = 5.54E-6) for rs625039, rs11190870 and rs11598564, respectively. Second, a case-only study including a subgroup of AIS patients (N = 234) was performed to determine the effects of these variants on the severity of the condition. However, we did not find any association between these variants and the severity of curvature.</p> <h3>Conclusion</h3><p>This study shows that the genetic variants near the <em>LBX1</em> gene are associated with AIS susceptibility in Chinese Han population. It successfully replicates the results of the GWAS, which was performed in a Japanese population.</p> </div

Linkage disequilibrium (LD) pattern and Haplotypes of the <i>Leptin</i> gene from the 45 healthy subjects.

<p>Two LD blocks were identified in the sequenced genomic region of the gene (calculated with the Solid spine of LD algorithm with the Minor Allele Frequency≥1%). Arrows indicate the positions of the 6 tag SNPs selected for the association study.</p

Comparison of all genes between AIS and control groups in adipogenesis assay.

<p>All <i>P</i> values were calculated with age adjusted.</p>*<p><i>P</i><0.05 was considered statistically significant.</p>**<p><i>P</i><0.01.</p

Gene expression levels in response to different doses of leptin.

<p>The expression levels in control group without leptin treatment were used as calibrators. Relative expression levels were calculated by using the 2^−ΔΔCt method.</p

r values of Correlations between the genes and parameters in AIS patients.

*<p><i>P</i><0.05 was considered statistically significant.</p>**<p><i>P</i><0.01.</p

Association between SNPs and the severity of spinal curvature in AIS.

a<p>Maximum Cobb angle (MCA).</p>b<p>β coefficients, standard errors and <i>P</i>-values were calculated using ordinary least squared regression.</p>c<p><i>P</i>-values were calculated using the Kruskal–Wallis test.</p

6 tag SNPs selected for the association study.

<p>6 tag SNPs selected for the association study.</p