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Mutation analysis biomarkers cancer

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https://www.readbyqxmd.com/read/28623901/biomarker-correlation-network-in-colorectal-carcinoma-by-tumor-anatomic-location
#1
Reiko Nishihara, Kimberly Glass, Kosuke Mima, Tsuyoshi Hamada, Jonathan A Nowak, Zhi Rong Qian, Peter Kraft, Edward L Giovannucci, Charles S Fuchs, Andrew T Chan, John Quackenbush, Shuji Ogino, Jukka-Pekka Onnela
BACKGROUND: Colorectal carcinoma evolves through a multitude of molecular events including somatic mutations, epigenetic alterations, and aberrant protein expression, influenced by host immune reactions. One way to interrogate the complex carcinogenic process and interactions between aberrant events is to model a biomarker correlation network. Such a network analysis integrates multidimensional tumor biomarker data to identify key molecular events and pathways that are central to an underlying biological process...
June 17, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28620130/circulating-microparticles-are-prognostic-biomarkers-in-advanced-non-small-cell-lung-cancer-patients
#2
Chin-Chou Wang, Chia-Cheng Tseng, Huang-Chih Chang, Kuo-Tung Huang, Wen-Feng Fang, Yu-Mu Chen, Cheng-Ta Yang, Chang-Chun Hsiao, Meng-Chih Lin, Chi-Kung Ho, Hon-Kan Yip
We investigated whether circulating microparticles (MPs) could serve as prognostic biomarkers in non-small cell lung cancer (NSCLC) patients. We enrolled 25 control subjects and 136 NSCLC patients categorized into disease-progression (DP, n=42) and disease-control (DC, n=94) groups. Flow cytometric analysis showed that levels of four types of circulating microparticles (EDAc-MPs, EDAp-MPs, PDAc-MPs and PDAp-MPs) were higher in the study patients than the control subjects (P < 0.04). DP patients showed poor initially performance status and more non-adenocarcinomas than DC patients...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28615531/environment-and-bladder-cancer-molecular-analysis-by-interaction-networks
#3
Andrea Polo, Anna Crispo, Pellegrino Cerino, Luca Falzone, Saverio Candido, Aldo Giudice, Giuseppina De Petro, Gennaro Ciliberto, Maurizio Montella, Alfredo Budillon, Susan Costantini
Bladder cancer (BC) is the 9th most common cancer worldwide, and the 6th most common cancer in men. Its development is linked to chronic inflammation, genetic susceptibility, smoking, occupational exposures and environmental pollutants. Aim of this work was to identify a sub-network of genes/proteins modulated by environmental or arsenic exposure in BC by computational network approaches. Our studies evidenced the presence of HUB nodes both in "BC and environment" and "BC and arsenicals" networks. These HUB nodes resulted to be correlated to circadian genes and targeted by some miRNAs already reported as involved in BC, thus suggesting how they play an important role in BC development due to environmental or arsenic exposure...
May 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28609226/phase-ii-trial-of-atezolizumab-as-first-line-or-subsequent-therapy-for-patients-with-programmed-death-ligand-1-selected-advanced-non-small-cell-lung-cancer-birch
#4
Solange Peters, Scott Gettinger, Melissa L Johnson, Pasi A Jänne, Marina C Garassino, Daniel Christoph, Chee Keong Toh, Naiyer A Rizvi, Jamie E Chaft, Enric Carcereny Costa, Jyoti D Patel, Laura Q M Chow, Marianna Koczywas, Cheryl Ho, Martin Früh, Michel van den Heuvel, Jeffrey Rothenstein, Martin Reck, Luis Paz-Ares, Frances A Shepherd, Takayasu Kurata, Zhengrong Li, Jiaheng Qiu, Marcin Kowanetz, Simonetta Mocci, Geetha Shankar, Alan Sandler, Enriqueta Felip
Purpose BIRCH was designed to examine the efficacy of atezolizumab, a humanized anti-programmed death-ligand 1 (PD-L1) monoclonal antibody, in advanced non-small-cell lung cancer (NSCLC) across lines of therapy. Patients were selected on the basis of PD-L1 expression on tumor cells (TC) or tumor-infiltrating immune cells (IC). Patients and Methods Eligible patients had advanced-stage NSCLC, no CNS metastases, and zero to two or more lines of prior chemotherapy. Patients whose tumors expressed PD-L1 using the SP142 immunohistochemistry assay on ≥ 5% of TC or IC (TC2/3 or IC2/3 [TC or IC ≥ 5% PD-L1-expressing cells, respectively]) were enrolled...
June 13, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28607607/microrna-signature-of-lung-adenocarcinoma-with-egfr-exon-19-deletion
#5
Lixia Ju, Mingquan Han, Xuefei Li, Chao Zhao
The findings of EGFR mutations and the development of targeted therapies have significantly improved the overall survival of lung cancer patients. Still, the prognosis remains poor, so we need to know more about the genetic alterations in lung cancer. MicroRNAs are dysregulated in lung cancer, and some of them can regulate EGFR. So it is very important to predict the candidate microRNAs that target mutated EGFR and to investigate the role of these candidate microRNAs in lung cancer. In this study, we investigated the difference of microRNAs expression between lung adenocarcinoma cell lines with EGFR exon 19 deletion (H1650 and PC9) and wild-type (H1299 and A549) using the Phalanx Human Whole Genome Microarray...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28592616/multicenter-phase-ii-study-of-panitumumab-in-platinum-pretreated-advanced-head-and-neck-squamous-cell-cancer
#6
Marco Siano, Francesca Molinari, Vittoria Martin, Nicolas Mach, Martin Früh, Stefania Freguia, Irene Corradino, Michele Ghielmini, Milo Frattini, Vittoria Espeli
LESSONS LEARNED: Panitumumab shows activity in terms of disease control rate and preventing disease progression but not for tumor shrinkage in head and neck squamous cell cancer for second-line treatment. Epidermal growth factor receptor (EGFR) copy number gain, a property of tumor cells that theoretically could identify patients more likely to experience disease response, was common among patients having disease control.Our trial, given the lower toxicity with an every-2-week schedule, provides guidance for future trials, for example, in combinations of immune therapies and anti-EGFR-antibodies...
June 7, 2017: Oncologist
https://www.readbyqxmd.com/read/28587748/liquid-biopsy-of-pik3ca-mutations-in-cervical-cancer-in-hong-kong-chinese-women
#7
Tony K H Chung, Tak Hong Cheung, So Fan Yim, Mei Yun Yu, Rossa W K Chiu, Keith W K Lo, Ida P C Lee, Raymond R Y Wong, Kitty K M Lau, Vivian W Wang, Michael J Worley, Kevin M Elias, Stephen J Fiascone, David I Smith, Ross S Berkowitz, Yick Fu Wong
INTRODUCTION: Cervical cancer is the fourth most common female cancer worldwide. The prognosis for women with advanced-stage or recurrent cervical cancer remains poor and response to treatment is variable. Standardized management protocols leave little room for individualization. We report on a novel blood-based liquid biopsy for specific PIK3CA mutations as a clinically useful biomarker in patients with invasive cervical cancer. METHODS: One hundred seventeen Hong Kong Chinese women with primary invasive cervical cancer and their pre-treatment plasma samples were investigated...
June 3, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28583311/next-generation-sequencing-of-nonmuscle-invasive-bladder-cancer-reveals-potential-biomarkers-and-rational-therapeutic-targets
#8
Eugene J Pietzak, Aditya Bagrodia, Eugene K Cha, Esther N Drill, Gopa Iyer, Sumit Isharwal, Irina Ostrovnaya, Priscilla Baez, Qiang Li, Michael F Berger, Ahmet Zehir, Nikolaus Schultz, Jonathan E Rosenberg, Dean F Bajorin, Guido Dalbagni, Hikmat Al-Ahmadie, David B Solit, Bernard H Bochner
BACKGROUND: Molecular characterization of nonmuscle invasive bladder cancer (NMIBC) may provide a biologic rationale for treatment response and novel therapeutic strategies. OBJECTIVE: To identify genetic alterations with potential clinical implications in NMIBC. DESIGN, SETTING, AND PARTICIPANTS: Pretreatment index tumors and matched germline DNA from 105 patients with NMIBC on a prospective Institutional Review Board-approved protocol underwent targeted exon sequencing analysis in a Clinical Laboratory Improvement Amendments-certified clinical laboratory...
June 2, 2017: European Urology
https://www.readbyqxmd.com/read/28583095/the-prognostic-significance-of-kras-and-braf-mutation-status-in-korean-colorectal-cancer-patients
#9
Daeyoun David Won, Jae Im Lee, In Kyu Lee, Seong-Taek Oh, Eun Sun Jung, Sung Hak Lee
BACKGROUND: BRAF and KRAS mutations are well-established biomarkers in anti-EGFR therapy. However, the prognostic significance of these mutations is still being examined. We determined the prognostic value of BRAF and KRAS mutations in Korean colorectal cancer (CRC) patients. METHODS: From July 2010 to September 2013, 1096 patients who underwent surgery for CRC at Seoul St. Mary's Hospital were included in the analysis. Resected specimens were examined for BRAF, KRAS, and microsatellite instability (MSI) status...
June 5, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28575854/genomic-alterations-in-mucins-across-cancers
#10
Ryan J King, Fang Yu, Pankaj K Singh
The significance of mucins in cancers has led to the development of novel biomarkers and therapeutic agents against cancers. Despite significant advances in the understanding of mucins, systemic investigations into the role of mucins in cancer biology focusing particularly on the histological subtypes and stages, along with other variables, are yet to be carried out to discover potential novel functions and cancer-specific roles. Here, we investigated 11 mucin expressing cancers for DNA mutations, mRNA expression, copy number, methylation, and the impacts these genomic features may have on patient survival by utilizing The Cancer Genome Atlas dataset...
May 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28566328/somatic-mutations-drive-distinct-imaging-phenotypes-in-lung-cancer
#11
Emmanuel Rios Velazquez, Chintan Parmar, Ying Liu, Thibaud P Coroller, Gisele Cruz, Olya Stringfield, Zhaoxiang Ye, G Mike Makrigiorgos, Fiona M M Fennessy, Raymond H Mak, Robert J Gillies, John Quackenbush, Hugo Aerts
Tumors are characterized by somatic mutations that drive biological processes ultimately reflected in tumor phenotype. With regard to radiographic phenotypes, generally unconnected through present understanding to the presence of specific mutations, artificial intelligence (AI) methods can automatically quantify phenotypic characters by using predefined, engineered algorithms or automatic deep-learning methods, a process also known as radiomics. Here we demonstrate how imaging phenotypes can be connected to somatic mutations through an integrated analysis of independent datasets of 763 lung adenocarcinoma patients with somatic mutation testing and engineered computed tomography (CT) image analytics...
May 31, 2017: Cancer Research
https://www.readbyqxmd.com/read/28550907/analysis-of-pik3ca-mutations-and-pi3k-pathway-proteins-in-advanced-gastric-cancer
#12
Chie Ito, Satoshi S Nishizuka, Kazuyuki Ishida, Noriyuki Uesugi, Tamotsu Sugai, Gen Tamura, Keisuke Koeda, Akira Sasaki
BACKGROUND: Although surgery and chemotherapy have extended advanced gastric cancer patient survival, some patients still experience relapse and metastasis. We postulated that PI3K pathway proteins could be prognostic biomarkers for the advanced gastric cancer patients. METHODS: A retrospective cohort of 160 advanced gastric cancer patients receiving potentially curative surgery with/without chemotherapy was investigated for PIK3CA mutation and PI3K pathway protein level in the context of overall survival and relapse-free survival...
May 15, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28544821/predictive-model-for-high-frequency-microsatellite-instability-in-colorectal-cancer-patients-over-50%C3%A2-years-of-age
#13
Kenji Fujiyoshi, Tatsuro Yamaguchi, Miho Kakuta, Akemi Takahashi, Yoshiko Arai, Mina Yamada, Gou Yamamoto, Sachiko Ohde, Misato Takao, Shin-Ichiro Horiguchi, Soichiro Natsume, Shinsuke Kazama, Yusuke Nishizawa, Yoji Nishimura, Yoshito Akagi, Hirohiko Sakamoto, Kiwamu Akagi
Microsatellite instability (MSI) is an important biomarker for screening for Lynch syndrome, and also of response to immune checkpoint inhibitors. The aim of this study is to create a predictive model to determine which elderly patients with colorectal cancer (CRC) should undergo MSI and/or immunohistochemistry testing on the basis of clinicopathological data. We analyzed a test cohort of CRC patients aged ≥50 years (n = 2219) by multivariate logistic regression analyses to identify predictors of high-frequency MSI (MSI-H)...
June 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28543104/circulating-tumor-dna-profiling-reveals-clonal-evolution-and-real-time-disease-progression-in-advanced-hepatocellular-carcinoma
#14
Zhi-Xiong Cai, Geng Chen, Yong-Yi Zeng, Xiu-Qing Dong, Min-Jie Lin, Xin-Hui Huang, Da Zhang, Xiao-Long Liu, Jing-Feng Liu
Circulating tumor DNA (ctDNA) provides a potential non-invasive biomarker for cancer diagnosis and prognosis, but whether it could reflect tumor heterogeneity and monitor therapeutic responses in hepatocellular carcinoma (HCC) is unclear. Focusing on 574 cancer genes known to harbor actionable mutations, we identified the mutation repertoire of HCC tissues, and monitored the corresponding ctDNA features in blood samples to evaluate its clinical significance. Analysis of 3 HCC patients' mutation profiles revealed that ctDNA could overcome tumor heterogeneity and provide information of tumor burden and prognosis...
May 22, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28537764/gefitinib-and-egfr-gene-copy-number-aberrations-in-esophageal-cancer
#15
Russell D Petty, Asa Dahle-Smith, David A J Stevenson, Aileen Osborne, Doreen Massie, Caroline Clark, Graeme I Murray, Susan J Dutton, Corran Roberts, Irene Y Chong, Wasat Mansoor, Joyce Thompson, Mark Harrison, Anirban Chatterjee, Stephen J Falk, Sean Elyan, Angel Garcia-Alonso, David Walter Fyfe, Jonathan Wadsley, Ian Chau, David R Ferry, Zosia Miedzybrodzka
Purpose The Cancer Esophagus Gefitinib trial demonstrated improved progression-free survival with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib relative to placebo in patients with advanced esophageal cancer who had disease progression after chemotherapy. Rapid and durable responses were observed in a minority of patients. We hypothesized that genetic aberration of the EGFR pathway would identify patients benefitting from gefitinib. Methods A prespecified, blinded molecular analysis of Cancer Esophagus Gefitinib trial tumors was conducted to compare efficacy of gefitinib with that of placebo according to EGFR copy number gain (CNG) and EGFR, KRAS, BRAF, and PIK3CA mutation status...
May 24, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28525846/exploring-the-clonal-evolution-of-cd133-aldehyde-dehydrogenase-1-aldh1-positive-cancer-stem-like-cells-from-primary-to-recurrent-high-grade-serous-ovarian-cancer-hgsoc-a-study-of-the-ovarian-cancer-therapy-innovative-models-prolong-survival-octips-consortium
#16
Ilary Ruscito, Dan Cacsire Castillo-Tong, Ignace Vergote, Iulia Ignat, Mandy Stanske, Adriaan Vanderstichele, Ram N Ganapathi, Jacek Glajzer, Hagen Kulbe, Fabian Trillsch, Alexander Mustea, Caroline Kreuzinger, Pierluigi Benedetti Panici, Charlie Gourley, Hani Gabra, Mirjana Kessler, Jalid Sehouli, Silvia Darb-Esfahani, Elena Ioana Braicu
BACKGROUND: High-grade serous ovarian cancer (HGSOC) causes 80% of all ovarian cancer (OC) deaths. In this setting, the role of cancer stem-like cells (CSCs) is still unclear. In particular, the evolution of CSC biomarkers from primary (pOC) to recurrent (rOC) HGSOCs is unknown. Aim of this study was to investigate changes in CD133 and aldehyde dehydrogenase-1 (ALDH1) CSC biomarker expression in pOC and rOC HGSOCs. METHODS: Two-hundred and twenty-four pOC and rOC intrapatient paired tissue samples derived from 112 HGSOC patients were evaluated for CD133 and ALDH1 expression using immunohistochemistry (IHC); pOCs and rOCs were compared for CD133 and/or ALDH1 levels...
May 16, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28525386/prognostic-value-of-kras-mutation-in-advanced-non-small-cell-lung-cancer-treated-with-immune-checkpoint-inhibitors-a-metaanalysis-and-review
#17
Jung Han Kim, Hyeong Su Kim, Bum Jun Kim
Immune checkpoint inhibitors (ICIs) have emerged as a promising treatment option in the fight against advanced non-small-cell lung cancer (NSCLC). KRAS is the most frequently mutated oncogene in NSCLC. We performed this meta-analysis to investigate if KRAS mutation status affects survival benefits of ICIs in patients with advanced NSCLC. Electronic databases were searched for eligible studies. We included randomized trials with the data of overall survival stratified by KRAS mutation status. From 3 eligible studies, 138 patients with KRAS mutant NSCLC and 371 with KRAS wild-type tumor were included in the meta-analysis...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28514740/differential-expression-of-circulating-biomarkers-of-tumor-phenotype-and-outcomes-in-previously-treated-non-small-cell-lung-cancer-patients-receiving-erlotinib-vs-cytotoxic-chemotherapy
#18
Mary Jo Fidler, Casey Frankenberger, Richard Seto, Gabriela C Lobato, Cristina L Fhied, Selina Sayidine, Sanjib Basu, Mark Pool, Reem Karmali, Marta Batus, Wen-Rong Lie, David Hayes, Jehangir Mistry, Philip Bonomi, Jeffrey A Borgia
BACKGROUND: The objective of this study was to identify serum biomarkers capable of predicting clinical outcomes in previously-treated NSCLC patients with wild-type for EGFR activating mutations or insufficient tissue for mutation status determination. METHODS: Sixty-six Luminex immunoassays representative of biological themes that emerged from a re-analysis of transcriptome data from the Cancer Genome Atlas (TCGA) were evaluate against pretreatment serum specimens from previously-treated advanced NSCLC patients received either cytotoxic chemotherapy (n=32) or erlotinib (n=79)...
April 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28512298/genetic-load-makes-cancer-cells-more-sensitive-to-common-drugs-evidence-from-cancer-cell-line-encyclopedia
#19
Ana B Pavel, Kirill S Korolev
Genetic alterations initiate tumors and enable the evolution of drug resistance. The pro-cancer view of mutations is however incomplete, and several studies show that mutational load can reduce tumor fitness. Given its negative effect, genetic load should make tumors more sensitive to anticancer drugs. Here, we test this hypothesis across all major types of cancer from the Cancer Cell Line Encyclopedia, which provides genetic and expression data of 496 cell lines together with their response to 24 common anticancer drugs...
May 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28507806/preclinical-efficacy-of-immune-checkpoint-monotherapy-does-not-recapitulate-corresponding-biomarkers-based-clinical-predictions-in-glioblastoma
#20
Abhishek D Garg, Lien Vandenberk, Matthias Van Woensel, Jochen Belmans, Marco Schaaf, Louis Boon, Steven De Vleeschouwer, Patrizia Agostinis
Glioblastoma (GBM) is resistant to most multimodal therapies. Clinical success of immune-checkpoint inhibitors (ICIs) has spurred interest in applying ICIs targeting CTLA4, PD1 or IDO1 against GBM. This amplifies the need to ascertain GBM's intrinsic susceptibility (or resistance) toward these ICIs, through clinical biomarkers that may also "guide and prioritize" preclinical testing. Here, we interrogated the TCGA and/or REMBRANDT human patient-cohorts to predict GBM's predisposition toward ICIs. We exploited various broad clinical biomarkers, including mutational or predicted-neoantigen burden, pre-existing or basal levels of tumor-infiltrating T lymphocytes (TILs), differential expression of immune-checkpoints within the tumor and their correlation with particular TILs/Treg-associated functional signature and prognostic impact of differential immune-checkpoint expression...
2017: Oncoimmunology
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