Li W.,BGI Shenzhen |
Xia Y.,BGI Shenzhen |
Xia Y.,Sun Yat Sen University |
Wang C.,BGI Shenzhen |
And 16 more authors.
PLoS ONE | Year: 2015
Copy-number variations (CNV), loss of heterozygosity (LOH), and uniparental disomy (UPD) are large genomic aberrations leading to many common inherited diseases, cancers, and other complex diseases. An integrated tool to identify these aberrations is essential in understanding diseases and in designing clinical interventions. Previous discovery methods based on whole-genome sequencing (WGS) require very high depth of coverage on the whole genome scale, and are cost-wise inefficient. Another approach, whole exome genome sequencing (WEGS), is limited to discovering variations within exons. Thus, we are lacking efficient methods to detect genomic aberrations on the whole genome scale using next-generation sequencing technology. Here we present a method to identify genomewide CNV, LOH and UPD for the human genome via selectively sequencing a small portion of genome termed Selected Target Regions (SeTRs). In our experiments, the SeTRs are covered by 99.73%-99.95% with sufficient depth. Our developed bioinformatics pipeline calls genome-wide CNVs with high confidence, revealing 8 credible events of LOH and 3 UPD events larger than 5M from 15 individual samples. We demonstrate that genome-wide CNV, LOH and UPD can be detected using a cost-effective SeTRs sequencing approach, and that LOH and UPD can be identified using just a sample grouping technique, without using a matched sample or familial information. © 2015 Li et al. Source
Wang F.,University of Jinan |
Wang F.,Shandong Academy of Sciences |
Fu P.,University of Jinan |
Pang Y.,Sishui People Hospital |
And 8 more authors.
Tumor Biology | Year: 2014
Telomerase reverse transcriptase (TERT) is the catalytic component of telomerase, especially the rate-limiting determinant of telomerase activity. Accumulating evidence has suggested that TERT could modulate the expression of numerous genes including interleukin 6 (IL-6), an important cytokine for the development of lung cancer. It has been reported that TERT polymorphism rs2736100T/G is associated with increased susceptibility to non-small cell lung cancer (NSCLC). However, the mechanism remains unclear. In the current study, we investigated the association between rs2736100T/G and NSCLC in 1,552 NSCLC and 1,602 healthy controls. Data revealed that the prevalence of TG and GG genotypes were significantly elevated in patients than in controls (odds ratio (OR)=1.18; 95% confidence interval (CI), 1.01-1.39; p=0.040 and OR=1.46; 95% CI, 1.19-1.78; p<0.001, respectively). The association was more prominent in patients with lung adenocarcinoma than those with squamous cell carcinoma (p=0.039). When analyzing the function of the polymorphism, we observed a significantly augmented level of IL-6 in subjects withGG genotype than those with GT and TT genotypes. Interestingly, the upregulation of IL-6 by GG genotype was 2.3-fold higher in lung adenocarcinoma compared to squamous cell carcinoma. These results suggest that the rs2736100T/G polymorphism modulates IL-6 expression and may play a unique role in lung adenocarcinoma. © International Society of Oncology and BioMarkers (ISOBM) 2014. Source
Cheng S.,University of Jinan |
Cheng S.,Shandong Academy of Sciences |
Zheng J.,Shandong Academy of Sciences |
Zhu J.,Weifang Hospital of Traditional Chinese Medicine |
And 7 more authors.
International Journal of Biological Markers | Year: 2015
Background: PD-1 and its ligand PD-L1 belong to the co-inhibition molecules, which can downregulate immune responses. The PD-L1 polymorphism and the level of soluble PD-L1 (sPD-L1) were investigated in non-small cell lung cancer (NSCLC). Methods: A total of 288 NSCLC patients and 300 controls were enrolled. An A/C polymorphism at position 8923 in the PD-L1 gene was genotyped using the polymerase chain reaction-restriction fragment length polymorphism method.Results: The prevalence of the 8923C allele was significantly higher in NSCLC patients than controls (10.2% versus 5.3%, p = 0.002, odds ratio 2.03, 95% confidence interval 1.30-3.17; data were adjusted for age and sex). NSCLC patients also showed increased plasma levels of sPD-L1 compared to controls (1.92 ng/mL versus 0.91 ng/mL, p<0.001). Furthermore, lung denocarcinoma patients had higher sPD-L1 levels than patients with squamous cell carcinoma (p<0.01). However, no association was observed between the different genetic variants and plasma concentrations of sPD-L1. Conclusions: The PD-L1 8923A/C polymorphism could be associated with increased susceptibility to NSCLC. Plasma levels of sPD-L1 are significantly increased in NSCLC patients, especially those with adenocarcinoma. © 2015 Wichtig Publishing. Source
Ma Y.,University of Jinan |
Ma Y.,Shandong Academy of Sciences |
Liu X.,Shandong Academy of Sciences |
Zhu J.,Weifang Hospital of Traditional Chinese Medicine |
And 7 more authors.
International Journal of Clinical and Experimental Medicine | Year: 2015
Lung cancer is a leading cause of cancer-related death in China, with non-small cell lung cancer (NSCLC) comprises the most common form. Co-inhibitory molecules, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death 1 (PD-1) and its ligand PD-L1, play a key roles in the physiopathological process of tumorigenesis. To investigate whether genetic variations of co-inhibitory molecules are associated with the risk of NSCLC, we analyzed polymorphisms of CTLA-4 (-318, +49), PD-1 (PD-1.1, PD-1.3, PD-1.5, PD-1.9) and PD-L1 (+8293) in a cohort of 528 NSCLC subjects and 600 healthy controls. By restriction fragment length polymorphism (RFLP) method, we found that the distributions of the CTLA-4 and PD-1 gene polymorphisms were similar between NSCLC patients and healthy controls. However, for the PD-L1 8923 A/C polymorphism, frequencies of the AC genotype and C-allele were significantly higher in NSCLC patients than in healthy controls (odds ratio [OR] =1.55; 95% confidence interval [CI] 1.13-2.13; P=0.006; OR=1.52; 95% CI 1.14-2.04; P=0.004, respectively). Stratification analysis revealed that prevalence of the 8923C allele was significantly increased in NSCLC patients who smoke compared to those non-smoking patients (OR=1.51; 95% CI 1.00-2.28; P<0.05). Moreover, NSCLC patients carrying the C-allele had higher risk of regional lymph node metastasis than those carrying the A-allele (OR=5.65; 95% CI 2.45~13.03; P<0.001). These data suggest that PD-L1+8293A>C polymorphism may play a role in the development and progression of NSCLC. © 2015, E-Century Publishing Corporation. All rights reserved. Source
Wang M.L.,Weifang Hospital of Traditional Chinese Medicine
Zhonghua nan ke xue = National journal of andrology | Year: 2012
Erectile dysfunction (ED), as a pathological phenomenon, refers to repeated or sustained difficulty to achieve and maintain sufficient penile erection to complete satisfactory sexual intercourse or sexual activity in male. The erectile reflex interruption induced by cavernous nerve (CN) damage is a direct cause of ED. In addition, the apoptosis of smooth muscle cells and endothelial cells in the corpus cavernosum caused by CN injury, along with the reduction of corpus cavernosum smooth muscle fibers, can increase the incidence of ED. Therefore, early intervention of the pathological process of CN injury and promotion of CN regeneration are essential for the treatment of ED. In recent years, the stem cell therapy for ED has become a focus in clinical research. This article offers an overview on the application of embryonic stem cells, mesenchymal stem cells, muscle-derived stem cells, and adipose stem cells in the treatment of ED. Source