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early stage lung cancer gene

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https://www.readbyqxmd.com/read/28202515/systematic-in-vivo-inactivation-of-chromatin-regulating-enzymes-identifies-setd2-as-a-potent-tumor-suppressor-in-lung-adenocarcinoma
#1
David M Walter, Olivia S Venancio, Elizabeth L Buza, John W Tobias, Charuhas Deshpande, A Andrea Gudiel, Caroline Kim-Kiselak, Michelle Cicchini, Travis J Yates, David M Feldser
Chromatin modifying genes are frequently mutated in human lung adenocarcinoma, but the functional impact of these mutations on disease initiation and progression is not well understood. Using a CRISPR-based approach, we systematically inactivated three of the most commonly mutated chromatin regulatory genes in two KrasG12D-driven mouse models of lung adenocarcinoma to characterize the impact of their loss. Targeted inactivation of SWI/SNF nucleosome remodeling complex members Smarca4 (Brg1) or Arid1a had complex effects on lung adenocarcinoma initiation and progression...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28197383/analysis-of-the-prognostic-role-of-an-immune-checkpoint-score-in-resected-non-small-cell-lung-cancer-patients
#2
Marta Usó, Eloísa Jantus-Lewintre, Silvia Calabuig-Fariñas, Ana Blasco, Eva García Del Olmo, Ricardo Guijarro, Miguel Martorell, Carlos Camps, Rafael Sirera
Tumors develop mechanisms to recruit tolerogenic immune cells and to induce the expression of molecules that act as immune checkpoints. This regulation of the immune microenvironment favors immune tolerance to the neoplastic cells. In this study, we have investigated the prognostic role of immune-checkpoint expression markers in a cohort of resectable non-small cell lung cancer (NSCLC) patients. RNA was isolated from fresh-frozen lung specimens (tumor and normal lung) (n = 178). RTqPCR was performed to analyze the relative expression of 20 immune-related genes that were normalized by the use of endogenous genes selected by GeNorm algorithm...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28194229/circulating-and-tissue-biomarkers-in-early-stage-non-small-cell-lung-cancer
#3
Caterina Fumagalli, Fabrizio Bianchi, Paola Rafaniello Raviele, Davide Vacirca, Giovanni Bertalot, Cristiano Rampinelli, Matteo Lazzeroni, Bernardo Bonanni, Giulia Veronesi, Nicola Fusco, Massimo Barberis, Elena Guerini-Rocco
OBJECTIVE: We sought to characterise circulating and tissue tumour biomarkers of patients who developed early-stage non-small cell lung cancer (NSCLC) during long-term follow-up of a chemoprevention trial (NCT00321893). MATERIALS AND METHODS: Blood and sputum samples were collected from 202 high-risk asymptomatic individuals with CT-detected stable lung nodules. Real-time PCR was performed on plasma to quantify free circulating DNA. Baseline serum was investigated with a previously validated test based on 13 circulating miRNAs (miR-Test)...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/28132868/lag-3-protein-expression-in-non-small-cell-lung-cancer-and-its-relationship-with-pd-1-pd-l1-and-tumor-infiltrating-lymphocytes
#4
Yayi He, Hui Yu, Leslie Rozeboom, Christopher J Rivard, Kim Ellison, Rafal Dziadziuszko, Kenichi Suda, Shengxiang Ren, Chunyan Wu, Likun Hou, Caicun Zhou, Fred R Hirsch
BACKGROUND: Immunotherapy targeting the programmed death-1 (PD-1) / programmed death ligand-1 (PD-L1) checkpoint has shown promising efficacy in patients with non-small cell lung cancer (NSCLC). Lymphocyte activation gene-3 (LAG-3) is another important checkpoint, and its role in NSCLC is still not clear. In this study, we investigated LAG-3 protein expression and its correlation with PD-1, PD-L1, tumor-infiltrating lymphocytes (TILs), and association with survival in NSCLC. METHODS: The expression of LAG-3 (EPR4392, Abcam) protein was assessed in 55 NSCLC cell lines by immunohistochemistry (IHC)...
January 26, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28126539/regional-emphysema-score-predicting-overall-survival-quality-of-life-and-pulmonary-function-recovery-in-early-stage-lung-cancer-patients
#5
Jie Dai, Ming Liu, Stephen J Swensen, Shawn M Stoddard, Jason A Wampfler, Andrew H Limper, Gening Jiang, Ping Yang
INTRODUCTION: Pulmonary emphysema is a common comorbidity in lung cancer, but its role in tumor prognosis remains obscure. Our aim was to evaluate the impact of the regional emphysema score (RES) on patient's overall survival, quality of life (QOL), and pulmonary function recovery in stage I-II lung cancer. METHODS: Between 1997 and 2009, 1,073 patients were identified and divided into two surgical groups (cancer in emphysematous [group 1, n=565] and non-emphysematous [group 2, n=435] region) and one non-surgical group (group 3, n=73)...
January 23, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28122330/a-novel-seven-long-non-coding-rna-signature-predicts-survival-in-early-stage-lung-adenocarcinoma
#6
Mingwei Chen, Baoquan Liu, Jianbing Xiao, Yingnan Yang, Yafang Zhang
Increasing evidence has revealed the significant association between dysregulated lncRNA expression and cancers. The prognostic value of lncRNAs in predicting the risk of disease recurrence and identifying high-risk subgroup of early stage lung adenocarcinoma (LUAD) is still unclear. In this study, we analyzed lncRNA expression profiles of 415 early-stage LUAD patients from Gene Expression Omnibus and identified a novel seven-lncRNA signature that was significantly associated with survival in patients with early-stage LUAD (HR = 2...
January 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28101350/tp53-mutation-is-associated-with-a-poor-clinical-outcome-for-non-small-cell-lung-cancer-evidence-from-a-meta-analysis
#7
Jincui Gu, Yanbin Zhou, Lixia Huang, Weijun Ou, Jian Wu, Shaoli Li, Junwen Xu, Jinlun Feng, Baomo Liu
A number of studies have examined the association between tumor protein 53 (TP53) mutations and the clinical outcome in patients with non-small-cell lung cancer (NSCLC), although these have yielded conflicting results. In the present study, electronic databases updated to September 2015 were searched to find relevant studies. A meta-analysis was performed on the eligible studies, which quantitatively evaluated the association between the TP53 mutations and the survival of patients with NSCLC. Subgroup and sensitivity analyses were performed...
December 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28098899/analysis-of-gene-expression-profiles-of-non-small-cell-lung-cancer-at-different-stages-reveals-significantly-altered-biological-functions-and-candidate-genes
#8
Jin Wang, Jianxiang Song, Zhengya Gao, Xudong Huo, Yajun Zhang, Wencai Wang, Jianwei Qi, Shiying Zheng
We attempt to dissect the pathology of non-small cell lung cancer (NSCLC) patients at different stages and discover the novel candidate genes. Microarray data (GSE21933) were retrieved from the Gene Expression Omnibus database. The differential expression profiles of lung tumor tissues during different stages were analyzed. The significantly altered functions and pathways were assessed and the key nodes in a protein-protein interaction (PPI) network were screened out. Then, the coexpression gene pairs and tumor-related genes were assessed...
January 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28088789/gprc5a-knockout-mouse-lung-epithelial-cells-predicts-ceruloplasmin-lipocalin-2-and-periostin-as-potential-biomarkers-at-early-stages-of-lung-tumorigenesis
#9
Beibei Sun, Wenzheng Guo, Song Hu, Feng Yao, Keke Yu, Jie Xing, Ronghua Wang, Hongyong Song, Yueling Liao, Tong Wang, Pengfei Jiang, Baohui Han, Jiong Deng
Lung cancer is the leading cause of cancer death. As most of lung cancer patients were diagnosed with the advanced stage, early detection is considered as the most effective strategy to reduce high mortality. Thus, it is desirable to identify specific biomarkers at early stages of lung tumorigenesis. GPRC5A is a lung tumor suppressor gene. GPRC5A deficiency is linked to lung cancer development. We hyposthesized that, dysregulated gene expression that results from Gprc5a deficiency may provide potential biomarkers at early stages of lung tumorigenesis...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28052056/genome-wide-in-vivo-screen-identifies-novel-host-regulators-of-metastatic-colonization
#10
Louise van der Weyden, Mark J Arends, Andrew D Campbell, Tobias Bald, Hannah Wardle-Jones, Nicola Griggs, Martin Del Castillo Velasco-Herrera, Thomas Tüting, Owen J Sansom, Natasha A Karp, Simon Clare, Diane Gleeson, Edward Ryder, Antonella Galli, Elizabeth Tuck, Emma L Cambridge, Thierry Voet, Iain C Macaulay, Kim Wong, Sarah Spiegel, Anneliese O Speak, David J Adams
Metastasis is the leading cause of death for cancer patients. This multi-stage process requires tumour cells to survive in the circulation, extravasate at distant sites, then proliferate; it involves contributions from both the tumour cell and tumour microenvironment ('host', which includes stromal cells and the immune system). Studies suggest the early steps of the metastatic process are relatively efficient, with the post-extravasation regulation of tumour growth ('colonization') being critical in determining metastatic outcome...
January 12, 2017: Nature
https://www.readbyqxmd.com/read/28024696/pik3ca-mutations-as-prognostic-factor-in-squamous-cell-lung-carcinoma
#11
Marc McGowan, Aleksandra Silye Hoven, Marius Lund-Iversen, Steinar Solberg, Åslaug Helland, Fred R Hirsch, Odd Terje Brustugun
OBJECTIVES: Mutation in the PIK3CA gene is reported frequent in squamous cell carcinomas of the lung, but its potential prognostic role is still obscure. We have studied the prognostic importance of PIK3CA mutations as well as the relation to other markers in a large number of early stage lung cancers of squamous carcinoma subtype. PATIENTS AND METHODS: Tumour tissue was obtained from 308 consecutively operated lung cancer patients with squamous cell carcinoma in the period 2003-2013...
January 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28008145/msh2-brca1-expression-as-a-dna-repair-signature-predicting-survival-in-early-stage-lung-cancer-patients-from-the-ifct-0002-phase-3-trial
#12
Guénaëlle Levallet, Fatéméh Dubois, Pierre Fouret, Martine Antoine, Solenn Brosseau, Emmanuel Bergot, Michèle Beau-Faller, Valérie Gounant, Elisabeth Brambilla, Didier Debieuvre, Olivier Molinier, Françoise Galateau-Sallé, Julien Mazieres, Elisabeth Quoix, Jean-Louis Pujol, Denis Moro-Sibilot, Alexandra Langlais, Franck Morin, Virginie Westeel, Gérard Zalcman
INTRODUCTION: DNA repair is a double-edged sword in lung carcinogenesis. When defective, it promotes genetic instability and accumulated genetic alterations. Conversely these defects could sensitize cancer cells to therapeutic agents inducing DNA breaks. METHODS: We used immunohistochemistry (IHC) to assess MSH2, XRCC5, and BRCA1 expression in 443 post-chemotherapy specimens from patients randomized in a Phase 3 trial, comparing two neoadjuvant regimens in 528 Stage I-II non-small cell lung cancer (NSCLC) patients (IFCT-0002)...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/27982019/the-associations-of-tert-clptm1l-variants-and-tert-mrna-expression-with-the-prognosis-of-early-stage-non-small-cell-lung-cancer
#13
Z Chen, J Wang, Y Bai, S Wang, X Yin, J Xiang, X Li, M He, X Zhang, T Wu, P Xu, H Guo
Lung cancer is the leading cause of cancer-related death in the world. Several genome-wide association studies (GWAS) have identified TERT-CLPTM1L as plausible causative locus for lung cancer development. This study aimed to investigate the associations of genetic variations in TERT-CLPTM1L and the expression level of TERT with the survival of early stage non-small cell lung cancer (NSCLC) patients. We selected three single-nucleotide polymorphisms of TERT-CLPTM1L (rs2853669, rs2736108 and rs31490) and genotyped in 140 early stage NSCLC patients by TaqMan assay...
December 16, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27955654/depletion-of-sag-rbx2-e3-ubiquitin-ligase-suppresses-prostate-tumorigenesis-via-inactivation-of-the-pi3k-akt-mtor-axis
#14
Mingjia Tan, Jie Xu, Javed Siddiqui, Felix Feng, Yi Sun
BACKGROUND: SAG (Sensitive to Apoptosis Gene), also known as RBX2, ROC2 or RNF7, is a RING component of CRL (Cullin-RING ligase), required for its activity. Our recent study showed that SAG/RBX2 co-operated with Kras to promote lung tumorigenesis, but antagonized Kras to inhibit skin tumorigenesis, suggesting a tissue/context dependent function of Sag. However, it is totally unknown whether and how Sag would play in prostate tumorigenesis, triggered by Pten loss. METHODS: Sag and Pten double conditional knockout mice were generated and prostate specific deletion of Sag and Pten was achieved by PB4-Cre, and their effect on prostate tumorigenesis was evaluated by H&E staining...
December 12, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27935865/bronchial-airway-gene-expression-signatures-in-mouse-lung-squamous-cell-carcinoma-and-their-modulation-by-cancer-chemopreventive-agents
#15
Donghai Xiong, Jing Pan, Qi Zhang, Eva Szabo, Mark Steven Miller, Ronald A Lubet, Ming You, Yian Wang
Due to exposure to environmental toxicants, a "field cancerization" effect occurs in the lung resulting in the development of a field of initiated but morphologically normal appearing cells in the damaged epithelium of bronchial airways with dysregulated gene expression patterns. Using a mouse model of lung squamous cell carcinoma (SCC), we performed transcriptome sequencing (RNA-Seq) to profile bronchial airway gene expression and found activation of the PI3K and Myc signaling networks in cytologically normal bronchial airway epithelial cells of mice with preneopastic lung SCC lesions, which was reversed by treatment with the PI3K Inhibitor XL-147 and pioglitazone, respectively...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926516/frequent-silencing-of-the-candidate-tumor-suppressor-trim58-by-promoter-methylation-in-early-stage-lung-adenocarcinoma
#16
Koichiro Kajiura, Kiyoshi Masuda, Takuya Naruto, Tomohiro Kohmoto, Miki Watabnabe, Mitsuhiro Tsuboi, Hiromitsu Takizawa, Kazuya Kondo, Akira Tangoku, Issei Imoto
In this study, we aimed to identify novel drivers that would be epigenetically altered through aberrant methylation in early-stage lung adenocarcinoma (LADC), regardless of the presence or absence of tobacco smoking-induced epigenetic field defects. Through genome-wide screening for aberrantly methylated CpG islands (CGIs) in 12 clinically uniform, stage-I LADC cases affecting six non-smokers and six smokers, we identified candidate tumor-suppressor genes (TSGs) inactivated by hypermethylation. Through systematic expression analyses of those candidates in panels of additional tumor samples and cell lines treated or not treated with 5-aza-deoxycitidine followed by validation analyses of cancer-specific silencing by CGI hypermethylation using a public database, we identified TRIM58 as the most prominent candidate for TSG...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/27915342/in-vitro-effects-of-has-2-gene-silencing-on-the-proliferation-and-apoptosis-of-the-mcf-7-human-breast-cancer-cell-line
#17
Hong-Yan Zhang, Feng Liang, Fei Wang, Jian-Wei Zhang, Li Wang, Xi-Gang Kang, Jie Wang, Qi-Liu Duan
BACKGROUND: Breast cancer is characterized by a distinct metastatic pattern involving the regional lymph nodes, bone marrow, lung and liver. This study is aimed to investigate the effects of silencing the HAS-2 gene on the proliferation and apoptosis of human breast cancer cells. METHODS: MCF-7 cells were collected and assigned into control, scrambled siRNA and HAS-2- siRNA groups. After transfection, the morphological changes in the MCF-7 cells were observed using phase contrast microscopy...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27867542/the-expression-of-sall4-is-significantly-associated-with-egfr-but-not-kras-or-eml4-alk-mutations-in-lung-cancer
#18
Xiangbo Jia, Rulin Qian, Binbin Zhang, Song Zhao
BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide; unfortunately, its prognosis is still very poor. Therefore, developing the target molecular is very important for lung cancer diagnosis and treatment, especially in the early stage. With this in view, spalt-like transcription factor 4 (SALL4) is considered a potential biomarker for diagnosis and prognosis in cancers, including lung cancer. METHODS: In order to better investigate the association between the expression of SALL4 and driver genes mutation, 450 histopathologically diagnosed patients with lung cancer and 11 non-cancer patients were enrolled to test the expression of SALL4 and the status of driver genes mutation...
October 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/27863400/differentiated-regulation-of-immune-response-related-genes-between-luad-and-lusc-subtypes-of-lung-cancers
#19
Mengzhu Chen, Xiuying Liu, Jie Du, Xiu-Jie Wang, Lixin Xia
Lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) are the two major subtypes of lung cancer, with LUSC exhibits faster progression rate than LUAD. To investigate the roles of immune-response related genes (IRGs) in lung cancer progression, we used LUAD and LUSC samples at different cancer progression stages, and identified that the expression profiles of IRGs could serve as a better classification marker for cancerous tissues of both LUAD and LUSC. We found that the expression changes of IRGs were different between LUAD and LUSC...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/27843638/kras-driven-lung-adenocarcinoma-combined-ddr1-notch-inhibition-as-an-effective-therapy
#20
REVIEW
Chiara Ambrogio, Ernest Nadal, Alberto Villanueva, Gonzalo Gómez-López, Timothy P Cash, Mariano Barbacid, David Santamaría
Understanding the early evolution of cancer heterogeneity during the initial steps of tumorigenesis can uncover vulnerabilities of cancer cells that may be masked at later stages. We describe a comprehensive approach employing gene expression analysis in early lesions to identify novel therapeutic targets and the use of mouse models to test synthetic lethal drug combinations to treat human Kirsten rat sarcoma viral oncogene homologue (KRAS)-driven lung adenocarcinoma.
2016: ESMO Open
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