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early stage lung cancer gene

Casina Kan, Geoffrey Vargas, François Le Pape, Philippe Clézardin
Bone metastases are a common complication of epithelial cancers, of which breast, prostate and lung carcinomas are the most common. The establishment of cancer cells to distant sites such as the bone microenvironment requires multiple steps. Tumour cells can acquire properties to allow epithelial-to-mesenchymal transition, extravasation and migration. Within the bone metastatic niche, disseminated tumour cells may enter a dormancy stage or proliferate to adapt and survive, interacting with bone cells such as hematopoietic stem cells, osteoblasts and osteoclasts...
October 4, 2016: International Journal of Molecular Sciences
Hong Tao, Yiran Cai, Liang Shi, Junfang Tang, Zhidong Liu, Zitong Wang, Lianqi Bai, Zhe Liu
BACKGROUND: Recent research into lung cancer-related driver genes has identified a distinctive molecular subtype of non-small cell lung cancer (NSCLC) - anaplastic lymphoma kinase (ALK)-positive NSCLC. We evaluated the clinical features and survival rates of ALK-positive lung adenocarcinoma patients who had undergone surgery but had not received ALK inhibitor therapy, along with the characteristics of patients with distant metastases. METHODS: Clinical data of 40 patients with ALK-positive, postsurgical lung adenocarcinoma were retrospectively analyzed...
October 24, 2016: Thoracic Cancer
Yun Su, HongBin Fang, Feng Jiang
BACKGROUND: Abnormal microRNA (miRNA) expressions and promoter methylation of genes detected in sputum may provide biomarkers for non-small lung cancer (NSCLC). Here, we evaluate the individual and combined analysis of the two classes of sputum molecular biomarkers for NSCLC detection. RESULTS: We analyze expression of 3 miRNAs (miR-21, miR-31, and miR-210) and methylation of 3 genes (RASSF1A, PRDM14, and 3OST2), which were previously identified as potential biomarkers for NSCLC, in sputum of a set of 117 stage I NSCLC patients and 174 cancer-free smokers...
2016: Clinical Epigenetics
Soon Young Shin, Chang Gun Kim, You Jung Jung, Yearam Jung, Hyeryoung Jung, Jihyun Im, Yoongho Lim, Young Han Lee
BACKGROUND: Breast cancer is the most common type of malignancy in women worldwide. Euphorbia humifusa Willd (EuH) is a plant that is widely used as a traditional medicine. However, no systemic studies on the anti-cancer effects of EuH have been reported. The aim of this study is to evaluate the anti-metastatic effect of the EuH. METHODS: Ethyl acetate fraction was prepared from EuH methanol extracts (EA/EuH). Inhibitory effect of EA/EuH on cell migration was determined using an in vitro scratch-wound healing assay...
October 24, 2016: BMC Complementary and Alternative Medicine
Touria Derkaoui, Joaira Bakkach, Mohamed Mansouri, Ali Loudiyi, Mohamed Fihri, Fatima Zahra Alaoui, Amina Barakat, Bouchra El Yemlahi, Hassan Bihri, Naima Ghailani Nourouti, Mohcine Bennani Mechita
BACKGROUND: Triple Negative Breast Cancer (TNBC) is defined by a lack of estrogen and progesterone receptor gene expression and by the absence of overexpression on HER2. It is associated to a poor prognosis. We propose to analyze the clinicopathologic and prognostic characteristics of this breast cancer subtype in a Mediterranean population originated or resident in the North of Morocco. METHODS: We conducted a retrospective study of 279 patients diagnosed with breast cancer between January 2010 and January 2015...
October 22, 2016: BMC Women's Health
Shin Yup Lee, Cheng Cheng Jin, Jin Eun Choi, Mi Jeong Hong, Deuk Kju Jung, Sook Kyung Do, Sun Ah Baek, Hyo Jung Kang, Hyo-Gyoung Kang, Sun Ha Choi, Won Kee Lee, Yangki Seok, Eung Bae Lee, Ji Yun Jeong, Kyung Min Shin, Sukki Cho, Seung Soo Yoo, Jaehee Lee, Seung Ick Cha, Chang Ho Kim, You Mie Lee, In-Kyu Lee, Sanghoon Jheon, Jae Yong Park
This study was conducted to investigate whether polymorphisms of genes involved in glycolysis are associated with the prognosis of patients with non-small cell lung cancer (NSCLC) after surgical resection. Forty-four single nucleotide polymorphisms (SNPs) of 17 genes in glycolytic pathway were investigated in a total of 782 patients with NSCLC who underwent curative surgical resection. The association of the SNPs with overall survival (OS) and disease free survival (DFS) were analyzed. Among the 44 SNPs investigated, four SNPs (ENO1 rs2274971A > G, PFKM rs11168417C > T, PFKP rs1132173C > T, PDK2 rs3785921G > A) were significantly associated with survival outcomes in multivariate analyses...
October 21, 2016: Scientific Reports
Alicia Hulbert, Ignacio Jusue Torres, Alejandro Stark, Chen Chen, Kristen Rodgers, Beverly Lee, Candace Griffin, Andrew Yang, Peng Huang, John Wrangle, Steven A Belinsky, Tza-Huei Wang, Stephen C Yang, Stephen B Baylin, Malcolm V Brock, James G Herman
PURPOSE: CT screening can reduce death from lung cancer. We sought to improve the diagnostic accuracy of lung cancer screening using ultrasensitive methods and a lung cancer specific gene panel to detect DNA methylation in sputum and Plasma. EXPERIMENTAL DESIGN: This is a case-control study of subjects with suspicious nodules on CT imaging. Plasma and sputum were obtained pre-operatively. Cases (n=150) had pathological confirmation of node negative (stage I and IIA) non-small cell lung cancer...
October 11, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Rongfei Han, Guanqun Huang, Yejun Wang, Yafei Xu, Yueming Hu, Wenqi Jiang, Tianfu Wang, Tian Xiao, Duo Zheng
Gene expression in metazoans is delicately organized. As genetic information transmits from DNA to RNA and protein, expression noise is inevitably generated. Recent studies begin to unveil the mechanisms of gene expression noise control, but the changes of gene expression precision in pathologic conditions like cancers are unknown. Here we analyzed the transcriptomic data of human breast, liver, lung and colon cancers, and found that the expression noise of more than 74.9% genes was increased in cancer tissues as compared to adjacent normal tissues...
October 4, 2016: Oncotarget
Seong-Min Park, Eun-Young Choi, Mingyun Bae, Sunshin Kim, Jong Bae Park, Heon Yoo, Jung Kyoon Choi, Youn-Jae Kim, Seung-Hoon Lee, In-Hoo Kim
Although several somatic single nucleotide variations in histone H3.3 have been investigated as cancer drivers, other types of aberration have not been well studied. Here, we demonstrate that overexpression of H3F3A, encoding H3.3, is associated with lung cancer progression and promotes lung cancer cell migration by activating metastasis-related genes. H3.3 globally activates gene expression through the occupation of intronic regions in lung cancer cells. Moreover, H3.3 binding regions show characteristics of regulatory DNA elements...
October 3, 2016: Nature Communications
H Kadara, M Choi, J Zhang, E P Cuentas, J R Canales, S G Gaffney, Z Zhao, C Behrens, J Fujimoto, C Chow, Y Yoo, N Kalhor, C Moran, D Rimm, S Swisher, D L Gibbons, J Heymach, E Kaftan, J P Townsend, T J Lynch, J Schlessinger, J Lee, R P Lifton, I I Wistuba, R S Herbst
BACKGROUND: Lung adenocarcinomas (LUADs) lead to the majority of deaths attributable to lung cancer. We performed whole-exome sequencing (WES) and immune profiling analyses of a unique set of clinically annotated early-stage LUADs to better understand the pathogenesis of this disease and identify clinically relevant molecular markers. METHODS: We performed WES of 108 paired stage I-III LUADs and normal lung tissues using the Illumina HiSeq 2000 platform. Ten immune markers (PD-L1, PD-1, CD3, CD4, CD8, CD45ro, CD57, CD68, FOXP3 and Granzyme B) were profiled by imaging-based immunohistochemistry in a subset of LUADs (n=92)...
September 29, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
M Choi, H Kadara, J Zhang, E P Cuentas, J R Canales, S G Gaffney, Z Zhao, C Behrens, J Fujimoto, C Chow, K Kim, N Kalhor, C Moran, D Rimm, S Swisher, D L Gibbons, J Heymach, E Kaftan, J P Townsend, T J Lynch, J Schlessinger, J Jack Lee, R P Lifton, R S Herbst, I I Wistuba
BACKGROUND: Lung squamous cell carcinoma (LUSC) accounts for 20-30% of non-small cell lung cancers (NSCLCs). There are limited treatment strategies for LUSC in part due to our inadequate understanding of the molecular underpinnings of the disease. We performed whole-exome sequencing (WES) and comprehensive immune profiling of a unique set of clinically annotated early-stage LUSCs to increase our understanding of the pathobiology of this malignancy. METHODS: Matched pairs of surgically resected stage I-III LUSCs and normal lung tissues (n=108) were analyzed by WES...
September 29, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Rintaro Noro, Teruhide Ishigame, Naomi Walsh, Kouya Shiraishi, Ana I Robles, Bríd M Ryan, Aaron J Schetter, Elise D Bowman, Judith A Welsh, Masahiro Seike, Akihiko Gemma, Vidar Skaug, Steen Mollerup, Aage Haugen, Jun Yokota, Takashi Kohno, Curtis C Harris
INTRODUCTION: There are no validated molecular methods that prospectively identify patients with surgically resected lung squamous cell carcinoma (SCC) at high risk for recurrence. By focusing on the expression of genes with known functions in development of lung SCC and prognosis, we sought to develop a robust prognostic classifier of early-stage lung SCC. METHODS: The expression of 253 genes selected by literature search was evaluated in microarrays from 107 stage I/II tumors...
September 6, 2016: Journal of Thoracic Oncology
Xiang Jin, Xingang Liu, Xiaodan Li, Yinghui Guan
Introduction. Lung adenocarcinoma (LAC) is the most frequent type of lung cancer and has a high metastatic rate at an early stage. This study is aimed at identifying LAC-associated genes. Materials and Methods. GSE62950 downloaded from Gene Expression Omnibus included a DNA methylation dataset and an mRNA expression profiles dataset, both of which included 28 LAC tissue samples and 28 adjacent normal tissue samples. The differentially expressed genes (DEGs) were screened by Limma package in R, and their functions were predicted by enrichment analysis using TargetMine online tool...
2016: BioMed Research International
Xindong Zhang, Lin Gao, Zhi-Ping Liu, Songwei Jia, Luonan Chen
As smoking rates decrease, proportionally more cases with lung adenocarcinoma occur in never-smokers, while aberrant DNA methylation has been suggested to contribute to the tumorigenesis of lung adenocarcinoma. It is extremely difficult to distinguish which genes play key roles in tumorigenic processes via DNA methylation-mediated gene silencing from a large number of differentially methylated genes. By integrating gene expression and DNA methylation data, a pipeline combined with the differential network analysis is designed to uncover driver methylation genes and responsive modules, which demonstrate distinctive expressions and network topology in tumors with aberrant DNA methylation...
2016: BioMed Research International
Christina I Selinger, Bob T Li, Nick Pavlakis, Matthew Links, Anthony J Gill, Adrian Lee, Stephen Clarke, Thang N Tran, Trina Lum, Po Yee Yip, Lisa Horvath, Bing Yu, Maija R J Kohonen-Corish, Sandra A O'Toole, Wendy A Cooper
AIMS: To assess the prevalence of ROS1 rearrangements in a retrospective and prospective diagnostic Australian cohort and evaluate the effectiveness of immunohistochemical screening. METHODS: A retrospective cohort of 278 early stage lung adenocarcinomas and an additional 104 prospective NSCLC cases referred for routine molecular testing were evaluated. ROS1 immunohistochemistry (IHC) was performed (D4D6 clone, Cell Signaling Technology) on all cases as well as fluorescence in situ hybridisation (FISH) using the ZytoVision and Abbott Molecular ROS1 FISH probes, with >15% of cells with split signals considered positive for rearrangement...
September 6, 2016: Histopathology
Gaia Cantelli, Eva Crosas-Molist, Mirella Georgouli, Victoria Sanz-Moreno
The Transforming Growth Factor-beta (TGFβ) pathway mediates a broad spectrum of cellular processes and is involved in several diseases, including cancer. TGFβ has a dual role in tumours, acting as a tumour suppressor in the early phase of tumorigenesis and as a tumour promoter in more advanced stages. In this review, we discuss the effects of TGFβ-driven transcription on all stages of tumour progression, with special focus on lung cancer. Since some TGFβ target genes are specifically involved in promoting metastasis, we speculate that these genes might be good targets to block tumour progression without compromising the tumour suppressor effects of the TGFβ pathway...
August 29, 2016: Seminars in Cancer Biology
Weiguo Zhang, Jian-Hua Mao, Wei Zhu, Anshu K Jain, Ke Liu, James B Brown, Gary H Karpen
Chromosomal instability (CIN) is a hallmark of cancer that contributes to tumour heterogeneity and other malignant properties. Aberrant centromere and kinetochore function causes CIN through chromosome missegregation, leading to aneuploidy, rearrangements and micronucleus formation. Here we develop a Centromere and kinetochore gene Expression Score (CES) signature that quantifies the centromere and kinetochore gene misexpression in cancers. High CES values correlate with increased levels of genomic instability and several specific adverse tumour properties, and prognosticate poor patient survival for breast and lung cancers, especially early-stage tumours...
2016: Nature Communications
Yi Han, Kang Shi, Shi-Jie Zhou, Da-Ping Yu, Zhi-Dong Liu
The hMLH1 gene plays an essential role in DNA repair. Methylation of the hMLH1 gene is common in many types of cancer and can lead to the loss of hMLH1 expression. However, the association and clinicopathological significance between hMLH1 promoter hypermethylation and non-small-cell lung cancer (NSCLC) is elusive. Here, we investigated the correlation of hMLH1 promoter hypermethylation and NSCLC using 13 studies by comprising 1,056 lung cancer patients via a meta-analysis. We observed that 1) loss of hMLH1 protein expression was significantly associated with its promoter hypermethylation, 2) hMLH1 gene inactivation through hypermethylation contributed to the tumorigenesis of NSCLC, which could be a decisive factor for the pathogenesis of NSCLC due to its high occurrence in NSCLC tissues compared to normal lung tissues, 3) a correlation exists between histologic subtypes/disease stages (TNM I+II vs III+IV) and hypermethylation status of hMLH1 gene, and 4) NSCLC patients with hMLH1 hypermethylation and subsequent low expression levels of hMLH1 have a short overall survival period than those patients with normal expression of hMLH1 gene...
2016: OncoTargets and Therapy
Karolina H Czarnecka, Monika Migdalska-Sęk, Daria Domańska, Dorota Pastuszak-Lewandoska, Agata Dutkowska, Jacek Kordiak, Ewa Nawrot, Justyna Kiszałkiewicz, Adam Antczak, Ewa Brzeziańska-Lasota
FHIT is a tumor suppressor gene that is frequently silenced in non-small cell lung cancer (NSCLC) and also in preneoplastic lesions. Promoter hypermethylation was previously observed in NSCLC, and its epigenetic silencing, observed on mRNA or protein level, was proposed to predict NSCLC outcome. In the present study we evaluated the relationship between FHIT expression on mRNA level and promoter methylation, or immunoexpression level. The aim of this study was to analyze the usefulness of FHIT as early differentiating biomarker in NSCLC patients...
September 2016: International Journal of Oncology
Ke-Zhong Chen, Feng Lou, Fan Yang, Jing-Bo Zhang, Hua Ye, Wei Chen, Tian Guan, Ming-Yu Zhao, Xue-Xia Su, Rong Shi, Lindsey Jones, Xue F Huang, Si-Yi Chen, Jun Wang
Circulating tumor DNA (ctDNA) isolated from peripheral blood has recently been shown to be an alternative source to detect gene mutations in primary tumors; however, most previous studies have focused on advanced stage cancers, and few have evaluated ctDNA detection in early-stage lung cancer. In the present study, blood and tumor samples were collected prospectively from 58 early-stage non-small lung cancer (NSCLC) patients (stages IA, IB, and IIA) and a targeted sequencing approach was used to detect somatic driver mutations in matched tumor DNA (tDNA) and plasma ctDNA...
2016: Scientific Reports
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