ABSTRACT
BACKGROUND@#Low-density computed tomography (LDCT) improved early lung cancer diagnosis but introduces an excess of false-positive pulmonary nodules data. Hence, accurate diagnosis of early-stage lung cancer remains challenging. The purpose of the study was to assess the feasibility of using circulating tumour cells (CTCs) to differentiate malignant from benign pulmonary nodules.@*METHODS@#122 patients with suspected malignant pulmonary nodules detected on chest CT in preparation for surgery were prospectively recruited. Peripheral blood samples were collected before surgery, and CTCs were identified upon isolation by size of epithelial tumour cells and morphological analysis. Laser capture microdissection, MALBAC amplification, and whole-exome sequencing were performed on 8 samples. The diagnostic efficacy of CTCs counting, and the genomic variation profile of benign and malignant CTCs samples were analysed.@*RESULTS@#Using 2.5 cells/5 mL as the cut-off value, the area under the receiver operating characteristic curve was of 0.651 (95% confidence interval: 0.538-0.764), with a sensitivity and specificity of 0.526 and 0.800, respectively, and positive and negative predictive values of 91.1% and 30.3%, respectively. Distinct sequence variations differences in DNA damage repair-related and driver genes were observed in benign and malignant samples. TP53 mutations were identified in CTCs of four malignant cases; in particular, g.7578115T>C, g.7578645C>T, and g.7579472G>C were exclusively detected in all four malignant samples.@*CONCLUSIONS@#CTCs play an ancillary role in the diagnosis of pulmonary nodules. TP53 mutations in CTCs might be used to identify benign and malignant pulmonary nodules.
Subject(s)
Humans , Lung Neoplasms , Exome Sequencing , Multiple Pulmonary Nodules , Carcinoma , DNA RepairABSTRACT
OBJECTIVE: An HLA imputation was conducted to explore the relationship between HLA and patients with moyamoya disease (MMD) in the Chinese Han population. METHODS: In this study, we performed an association analysis of the major histocompatibility complex region in 2,786 individuals of Chinese Han ancestry (2,031 controls and 755 patients with MMD), through a widely used HLA imputation method. RESULTS: We identified that the variant rs3129731 (odds ratio [OR] = 1.79, p = 3.69 × 10-16) located between the MTCO3P1 and HLA-DQA2 is a major genetic risk factor for MMD. In addition to this variant, found in the conditional association analysis, we also detected another independent signal, rs1071817 (OR = 0.62, p = 1.20 × 10-11), in HLA-B. CONCLUSIONS: Our research suggests that the genetic polymorphism of HLA-DQA2 and HLA-B could be a genetic predisposing factor for MMD in Chinese Han. This may provide some evidence for further HLA-related studies of patients with MMD of Chinese Han ethnicity and indicates that MMD is an immune-related disease.
ABSTRACT
BACKGROUND: Both stroke and depression are multi-factorial diseases, with both genetic and environmental factors likely to participate in their pathogenesis. Post stroke depression (PSD) is a common complication after stroke leading to poor functional outcome, increased physical disability and mortality. Although several genes have been associated with PSD, the genetic basis of PSD remains poorly understood. METHOD: A 2-stage candidate gene study by targeted sequencing was conducted involving stroke patients with or without depression and health controls. In the discovery stage (121 PSD, 131 non-PSD and 639 HC), logistic regression was used to test associations respectively in PSD and non-PSD groups. In the replication stage (200 PSD, 218 non-PSD and 983 HC), 54 selected SNPs were again genotyped in an independent cohort. Fixed-effects inverse variance-weighted meta-analysis was used in the combined samples. RESULTS: The study identified 2 novel genes associated with PSD [HTR3D (rs55674402, pâ¯=â¯0.002512, odds ratio (OR)â¯=â¯0.7431); NEUROG3 (rs144643855, pâ¯=â¯0.00325, ORâ¯=â¯0.6523)] and 3 risk SNPs in one risk gene associated with non-PSD [PIK3C2B (rs17406271, pâ¯=â¯0.0006801, ORâ¯=â¯1.446; rs2271419, pâ¯=â¯0.0005836, ORâ¯=â¯1.497; rs2271420, pâ¯=â¯0.001031, ORâ¯=â¯1.431)] in the Chinese sample. NEUROG3 shows highest expression level in hippocampus. Functional enrichment analysis shows that susceptibility genes for PSD are mostly enriched in chemical synaptic transmission and regulation of lipid synthetic process. LIMITATIONS: The sample size was not sufficient to reach a genome-wide p value level. To overcome this shortage, some unique strategies were applied during the selection of SNPs for replication. Secondly, the age, gender composition and depressive severity between two stages were not well-matched. Different sample sources should be blamed, and to minimizing the influence, gender was corrected as co-variant in logistic regression. CONCLUSION: This study identified that HTR3D and NEUROG3 were linked with the susceptibility of PSD and PIK3C2B with stroke in the Chinese Han population. Further replication of these findings in a larger and better matched sample is warranted. Functional analysis suggests that the pathogenesis of PSD may be implicated in 5-HT synaptic transmission, neural plasticity and lipid metabolism, and therapeutic interventions targeting these pathways may be effective approaches for PSD treatment.
