Abstract：
:Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3064 credible risk variants for NSCLC, which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER = 1.95, P = 0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.
journal_name
Front Medjournal_title
Frontiers of medicineauthors
Qin N,Li Y,Wang C,Zhu M,Dai J,Hong T,Albanes D,Lam S,Tardon A,Chen C,Goodman G,Bojesen SE,Landi MT,Johansson M,Risch A,Wichmann HE,Bickeboller H,Rennert G,Arnold S,Brennan P,Field JK,Shete S,Le Marchand L,Medoi
10.1007/s11684-020-0779-4subject
Has Abstractpub_date
2020-09-05 00:00:00eissn
2095-0217issn
2095-0225pii
10.1007/s11684-020-0779-4pub_type
杂志文章abstract：:Antitumor angiogenic therapy has been shown promising in the treatment of several advanced cancers since the approval of the first antiangiogenic drug Avastin in 2004. Although the current antiangiogenic drugs reduce the density of tumor blood vessels and result in tumor shrinkage at the early stage of treatment, rece...
journal_title：Frontiers of medicine
pub_type： 杂志文章,评审
doi：10.1007/s11684-012-0176-8
更新日期：2012-03-01 00:00:00
abstract：:Tissue factor pathway inhibitor (TFPI) is the main inhibitor of tissue factor-mediated coagulation. TFPI is expressed by endothelial and smooth muscle cells in the vasculature. Endothelium-derived TFPI has been reported to play a regulatory role in arterial thrombosis. However, the role of endogenous TFPI in vascular ...
journal_title：Frontiers of medicine
pub_type： 杂志文章
doi：10.1007/s11684-017-0522-y
更新日期：2017-09-01 00:00:00
abstract：:Growing evidence suggests that somatic hypermutational status and programmed cell death-1 overexpression are potential predictive biomarkers indicating treatment benefits from immunotherapy using immune checkpoint inhibitors. However, biomarker-matched trials are still limited, and many of the genomic alterations rema...
journal_title：Frontiers of medicine
pub_type： 杂志文章,多中心研究
doi：10.1007/s11684-019-0698-4
更新日期：2020-02-01 00:00:00
abstract：:This study evaluated the immunogenicity and protective immunity of a Hemophilus influenzae b (Hib) polysaccharide conjugate vaccine with the pneumococcal surface adhesin A (PsaA) protein carrier in young mice. The Hib polysaccharide was conjugated with the rPsaA protein carrier, which was produced using recombinant DN...
journal_title：Frontiers of medicine
pub_type： 杂志文章
doi：10.1007/s11684-016-0470-y
更新日期：2016-12-01 00:00:00
abstract：:The inhibitory environment that surrounds the lesion site and the lack of intrinsic regenerative capacity of the adult mammalian central nervous system (CNS) impede the regrowth of injured axons and thereby the reestablishment of neural circuits required for functional recovery after spinal cord injuries (SCI). To cir...
journal_title：Frontiers of medicine
pub_type： 杂志文章,评审
doi：10.1007/s11684-018-0642-z
更新日期：2019-04-01 00:00:00
abstract：:An effective eradication therapy of Helicobacter pylori (H. pylori) should be used for the first time. In this study, we assessed whether tailored therapy based on antibiotic susceptibility testing is more effective than traditional therapy. We also evaluated the factors that cause treatment failure in high-resistance...
journal_title：Frontiers of medicine
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1007/s11684-019-0706-8
更新日期：2020-02-01 00:00:00
abstract：:Recent evidences suggested that cyclic guanosine monophosphate-specific phosphodiesterase 5 (PDE5) inhibitor represents an important therapeutic target for cardiovascular diseases. Whether and how it ameliorates cardiac fibrosis, a major cause of diastolic dysfunction and heart failure, is unknown. The purpose of this...
journal_title：Frontiers of medicine
pub_type： 杂志文章
doi：10.1007/s11684-014-0378-3
更新日期：2014-12-01 00:00:00
abstract：:A high level of social support can improve long-term diabetes self-management. Support from a single source has been evaluated. This study aims to analyze support from multiple and multilevel sources for diabetic patients by using the Chronic Illness Resources Survey (CIRS). Factors influencing the utilization of the ...
journal_title：Frontiers of medicine
pub_type： 杂志文章,多中心研究
doi：10.1007/s11684-016-0441-3
更新日期：2016-06-01 00:00:00
abstract：:Pulmonary hypertension (PH), as a complication of bronchiectasis, is associated with increased mortality. However, hemodynamic characteristics and the efficacy of pulmonary arterial hypertension (PAH) therapies in patients with bronchiectasis and PH remain unknown. Patients with bilateral bronchiectasis and concurrent...
journal_title：Frontiers of medicine
pub_type： 杂志文章
doi：10.1007/s11684-016-0461-z
更新日期：2016-09-01 00:00:00
abstract：:Electroacupuncture (EA) at Zhongliao (BL33) can improve the symptoms of overactive bladder (OAB), such as urinary frequency, urgency, and incontinence. However, its performance compared with other acupoints remains unclear. This study investigated the effects of EA at BL33 with deep needling on rats with OAB by detect...
journal_title：Frontiers of medicine
pub_type： 杂志文章
doi：10.1007/s11684-016-0491-6
更新日期：2017-03-01 00:00:00
abstract：:Chromosomal aberrations have been associated with cancer development since their discovery more than a hundred years ago. Chromosomal translocations, a type of particular structural changes involving heterologous chromosomes, have made a critical impact on diagnosis, prognosis and treatment of cancers. For example, th...
journal_title：Frontiers of medicine
pub_type： 杂志文章,评审
doi：10.1007/s11684-012-0215-5
更新日期：2012-09-01 00:00:00
abstract：:This study aimed to evaluate the efficacy of Chinese herbal medicine (CHM) in patients with severe/critical coronavirus disease 2019 (COVID-19). In this retrospective study, data were collected from 662 patients with severe/critical COVID-19 who were admitted to a designated hospital to treat patients with severe COVI...
journal_title：Frontiers of medicine
pub_type： 杂志文章
doi：10.1007/s11684-020-0813-6
更新日期：2020-12-01 00:00:00
abstract：:This study aims to investigate the effect of non-transecting anastomotic urethroplasty for treatment of posterior urethral stricture. A total of 23 patients with traumatic posterior urethral stricture were enrolled and then divided into two groups. In one group, 12 patients underwent non-transecting anastomotic urethr...
journal_title：Frontiers of medicine
pub_type： 杂志文章
doi：10.1007/s11684-017-0515-x
更新日期：2017-06-01 00:00:00
abstract：:Cleft lip and palate (CLP) is the most common craniofacial congenital deformity. The etiology of CLP is multifactorial and involves complex interactions between environmental and genetic factors. Millard's rotation advancement technique has long been considered as state-of-the-art for unilateral cleft lip repair. Howe...
journal_title：Frontiers of medicine
pub_type： 杂志文章
doi：10.1007/s11684-013-0299-6
更新日期：2013-12-01 00:00:00
abstract：:γδ T cells display unique developmental, distributional, and functional patterns and can rapidly respond to various insults and contribute to diverse diseases. Different subtypes of γδ T cells are produced in the thymus prior to their migration to peripheral tissues. γδ T cells are enriched in the liver and exhibit li...
journal_title：Frontiers of medicine
pub_type： 杂志文章,评审
doi：10.1007/s11684-017-0584-x
更新日期：2018-06-01 00:00:00
abstract：:Swallowing multiple magnets is not uncommon worldwide and it frequently leads to serious consequences. However, most patients fail to receive timely and correct diagnosis and treatment. A literature search was performed to establish an algorithm for these accidents by the authors to identify relevant articles publishe...
journal_title：Frontiers of medicine
pub_type： 杂志文章,评审
doi：10.1007/s11684-012-0207-5
更新日期：2012-09-01 00:00:00
abstract：:Laparoscopic liver surgery has been increasingly used for the treatment of pediatric liver diseases over the past decade due to the development of special laparoscopic instruments and improvements in the technique. A number of factors are considered when electing to undergo the surgical process, including age, type of...
journal_title：Frontiers of medicine
pub_type： 杂志文章,评审
doi：10.1007/s11684-011-0165-3
更新日期：2011-12-01 00:00:00
abstract：:Chimeric antigen receptor T (CAR-T) cell therapy is a novel cellular immunotherapy that is widely used to treat hematological malignancies, including acute leukemia, lymphoma, and multiple myeloma. Despite its remarkable clinical effects, this therapy has side effects that cannot be underestimated. Cytokine release sy...
journal_title：Frontiers of medicine
pub_type： 杂志文章
doi：10.1007/s11684-019-0714-8
更新日期：2019-10-01 00:00:00
abstract：:Foodborne disease is one of the most important public health issues worldwide. China faces various and unprecedented challenges in all aspects of the food chain. Data from laboratory-based foodborne disease surveillance systems from 2013 to 2016, as well as different regions and ages, can be found along with differenc...
journal_title：Frontiers of medicine
pub_type： 杂志文章,评审
doi：10.1007/s11684-017-0608-6
更新日期：2018-02-01 00:00:00
abstract：:Inappropriate cell proliferation during oncogenesis is often accompanied by inactivation of components involved in the cell cycle machinery. Here, we report that cyclin-dependent kinase inhibitor 2C (CDKN2C) as a member of the cyclin-dependent kinase inhibitors is a target of the PML/RARα oncofusion protein in leukemo...
journal_title：Frontiers of medicine
pub_type： 杂志文章
doi：10.1007/s11684-016-0478-3
更新日期：2016-12-01 00:00:00
abstract：:At present, clinical pathway has become one of the most important health care reform measures in many countries. In this study, the authors introduced basic concepts and explored the application of the clinical pathway of evidence-based Chinese medicine incorporated with the methodology from the concepts of management...
journal_title：Frontiers of medicine
pub_type： 杂志文章,评审
doi：10.1007/s11684-011-0128-8
更新日期：2011-06-01 00:00:00
abstract：:Infection with Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 as an important respiratory disease with high fatality rates of 40%-60%. Despite the increased number of cases over subsequent years, the number of pediatric cases remained low. A review of studies conducted from June 2012 to April ...
journal_title：Frontiers of medicine
pub_type： 杂志文章
doi：10.1007/s11684-017-0603-y
更新日期：2019-02-01 00:00:00
abstract：:Ventricular hypertrophy is a powerful and independent predictor of cardiovascular morbid events. The vascular properties of low-dose acetyl salicylic acid (aspirin) provide cardiovascular benefits through the irreversible inhibition of platelet cyclooxygenase 1; however, the possible anti-hypertrophic properties and p...
journal_title：Frontiers of medicine
pub_type： 杂志文章
doi：10.1007/s11684-015-0421-z
更新日期：2015-12-01 00:00:00
abstract：:This study aimed to explore the association of maternal depression with nutrient intake, growth, and development of preterm infants. A cohort study of 201 infants was conducted in Beijing. Based on the gestational age of an infant and status of the mother, the infants were divided into four groups: non-depression-full...
journal_title：Frontiers of medicine
pub_type： 杂志文章
doi：10.1007/s11684-017-0591-y
更新日期：2018-10-01 00:00:00
abstract：:Sepsis is a common cause of death in hospitalized patients worldwide. The early detection of sepsis remains a great challenge for clinicians, and delayed diagnosis frequently undermines treatment efforts, thereby contributing to high mortality. Omics technologies allow high-throughput screening of sepsis biomarkers. T...
journal_title：Frontiers of medicine
pub_type： 杂志文章,评审
doi：10.1007/s11684-014-0318-2
更新日期：2014-03-01 00:00:00
abstract：:Zebrafish is an emerging animal model for studies on auditory system. This model presents high comparability with humans, good accessibility to the hearing organ, and high throughput capacity. To better utilize this animal model, methodologies need to be used to quantify the hearing function of the zebrafish. Zebrafis...
journal_title：Frontiers of medicine
pub_type： 杂志文章,评审
doi：10.1007/s11684-017-0507-x
更新日期：2017-06-01 00:00:00
abstract：:NUP98 fuses with approximately 34 different partner genes via translocation in hematological malignancies. Transgenic or retrovirus-mediated bone marrow transplanted mouse models reveal the leukemogenesis of some NUP98-related fusion genes. We previously reported the fusion protein NUP98-IQ motif containing G (IQCG) i...
journal_title：Frontiers of medicine
pub_type： 杂志文章
doi：10.1007/s11684-016-0489-0
更新日期：2016-12-01 00:00:00
abstract：:It has been known that, the novel coronavirus, 2019-nCoV, which is considered similar to SARS-CoV, invades human cells via the receptor angiotensin converting enzyme II (ACE2). Moreover, lung cells that have ACE2 expression may be the main target cells during 2019-nCoV infection. However, some patients also exhibit no...
journal_title：Frontiers of medicine
pub_type： 杂志文章
doi：10.1007/s11684-020-0754-0
更新日期：2020-04-01 00:00:00
abstract：:The aim of this study was to investigate the clinical characteristics of neonates born to SARS-CoV-2 infected mothers and increase the current knowledge on the perinatal consequences of COVID-19. Nineteen neonates were admitted to Tongji Hospital from January 31 to February 29, 2020. Their mothers were clinically diag...
journal_title：Frontiers of medicine
pub_type： 杂志文章
doi：10.1007/s11684-020-0772-y
更新日期：2020-04-01 00:00:00
abstract：:Alternative splicing plays a fundamental role in the development and physiological function of the inner ear. Inner-ear-specific gene splicing is necessary to establish the identity and maintain the function of the inner ear. For example, exon 68 of Cadherin 23 (Cdh23) gene is subject to inner-ear-specific alternative...
journal_title：Frontiers of medicine
pub_type： 杂志文章,评审
doi：10.1007/s11684-016-0454-y
更新日期：2016-09-01 00:00:00
