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Grant Details

Grant Number: 5R01CA176568-05 Interpret this number
Primary Investigator: Gu, Jian
Organization: University Of Tx Md Anderson Can Ctr
Project Title: Epigenetic Mirna, Snp Signatures, and Their Functions in Lung Cancer Outcomes
Fiscal Year: 2018
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Abstract

DESCRIPTION (provided by applicant): Non-small cell lung cancer (NSCLC) comprises over 80% of all lung cancer cases. More than two-thirds of NSCLC are diagnosed at a late stage, when current treatments are largely ineffective and only benefit a small portion of patients. Clinical variables alone cannot satisfactorily predict patients' outcomes. Biomarkers are urgently needed to assist in the patient stratification for personalized cancer therapy. Novel therapeutic agents are also highly desired to give patients alternative options after improved prediction of outcomes of treatments. The goals of this project are to identify germline genetic and circulating biomarkers related to microRNA (miRNA) as predictors of survival in late stage NSCLC patients. MiRNAs can regulate up to a third of human genes and play important roles in human carcinogenesis. The inherited genetic variants, mostly in the form of single nucleotide polymorphisms (SNPs), particularly SNPs in miRNA regulatory pathways (miR-SNPs), can also affect expression and/or function of their host and target genes. We propose to conduct a systematic study of miR-SNPs and circulating miRNAs in lung cancer. This proposal builds upon a lung cancer population at MD Anderson Cancer Center, with comprehensive epidemiological and clinical data and rich bio specimens. There are three specific aims: 1) to identify novel germline genetic loci in miR-SNPs that predict survival in patients with late-stage NSCLC. We will use a discovery and validation design with each phase consisting of 1,200 patients for platinum-treated patients; 2) to identify circulating miRNAs as predictors of survival in late- stage NSCLC patients using a testing and a validation set with a total of 800 plasma samples; and 3) to determine the potential disease-causative structural context, biological function, and molecular mechanism of the identified epigenetic miR-SNP and circulating miRNA biomarkers. This is a significant and innovative project incorporating epidemiology, inherited genetics, circulating biomarkers, biological and mechanistic studies, and preclinical therapeutic development.

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Publications

Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk.
Authors: Ji X. , BossÚ Y. , Landi M.T. , Gui J. , Xiao X. , Qian D. , Joubert P. , Lamontagne M. , Li Y. , Gorlov I. , et al. .
Source: Nature Communications, 2018-08-13 00:00:00.0; 9(1), p. 3221.
EPub date: 2018-08-13 00:00:00.0.
PMID: 30104567
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Stage Dependence, Cell-Origin Independence, and Prognostic Capacity of Serum Glycan Fucosylation, ?1-4 Branching, ?1-6 Branching, and ?2-6 Sialylation in Cancer.
Authors: Ferdosi S. , Rehder D.S. , Maranian P. , Castle E.P. , Ho T.H. , Pass H.I. , Cramer D.W. , Anderson K.S. , Fu L. , Cole D.E.C. , et al. .
Source: Journal Of Proteome Research, 2018-01-05 00:00:00.0; 17(1), p. 543-558.
EPub date: 2017-11-21 00:00:00.0.
PMID: 29129073
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Circulating metabolite profiles to predict overall survival in advanced non-small cell lung cancer patients receiving first-line chemotherapy.
Authors: Shen J. , Ye Y. , Chang D.W. , Huang M. , Heymach J.V. , Roth J.A. , Wu X. , Zhao H. .
Source: Lung Cancer (amsterdam, Netherlands), 2017 Dec; 114, p. 70-78.
EPub date: 2017-11-02 00:00:00.0.
PMID: 29173770
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Polymorphisms in genes related to epithelial-mesenchymal transition and risk of non-small cell lung cancer.
Authors: Xie K. , Ye Y. , Zeng Y. , Gu J. , Yang H. , Wu X. .
Source: Carcinogenesis, 2017-10-01 00:00:00.0; 38(10), p. 1029-1035.
PMID: 28968839
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Common, germline genetic variations in the novel tumor suppressor BAP1 and risk of developing different types of cancer.
Authors: Lin M. , Zhang L. , Hildebrandt M.A.T. , Huang M. , Wu X. , Ye Y. .
Source: Oncotarget, 2017-09-26 00:00:00.0; 8(43), p. 74936-74946.
EPub date: 2017-08-24 00:00:00.0.
PMID: 29088836
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Serum MicroRNA-150 Predicts Prognosis for Early-Stage Non-Small Cell Lung Cancer and Promotes Tumor Cell Proliferation by Targeting Tumor Suppressor Gene SRCIN1.
Authors: Zhang L. , Lin J. , Ye Y. , Oba T. , Gentile E. , Lian J. , Wang J. , Zhao Y. , Gu J. , Wistuba I.I. , et al. .
Source: Clinical Pharmacology And Therapeutics, 2017-09-10 00:00:00.0; , .
EPub date: 2017-09-10 00:00:00.0.
PMID: 28891208
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A miR-SNP biomarker linked to an increased lung cancer survival by miRNA-mediated down-regulation of FZD4 expression and Wnt signaling.
Authors: Lin J. , Zandi R. , Shao R. , Gu J. , Ye Y. , Wang J. , Zhao Y. , Pertsemlidis A. , Wistuba I.I. , Wu X. , et al. .
Source: Scientific Reports, 2017-08-22 00:00:00.0; 7(1), p. 9029.
EPub date: 2017-08-22 00:00:00.0.
PMID: 28831115
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Cationic liquid crystalline nanoparticles for the delivery of synthetic RNAi-based therapeutics.
Authors: Gentile E. , Oba T. , Lin J. , Shao R. , Meng F. , Cao X. , Lin H.Y. , Mourad M. , Pataer A. , Baladandayuthapani V. , et al. .
Source: Oncotarget, 2017-07-18 00:00:00.0; 8(29), p. 48222-48239.
PMID: 28637023
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Hypoxia pathway genetic variants predict survival of non-small-cell lung cancer patients receiving platinum-based chemotherapy.
Authors: Li R. , Gu J. , Heymach J.V. , Shu X. , Zhao L. , Han B. , Ye Y. , Roth J. , Wu X. .
Source: Carcinogenesis, 2017-04-01 00:00:00.0; 38(4), p. 419-424.
PMID: 28186269
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Microrna-mediated Target Mrna Cleavage And 3'-uridylation In Human Cells
Authors: Xu K. , Lin J. , Zandi R. , Roth J.A. , Ji L. .
Source: Scientific Reports, 2016-07-21 00:00:00.0; 6, p. 30242.
PMID: 27440378
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Detection Of Sirna-mediated Target Mrna Cleavage Activities In Human Cells By A Novel Stem-loop Array Rt-pcr Analysis
Authors: Lin J. , Xu K. , Roth J.A. , Ji L. .
Source: Biochemistry And Biophysics Reports, 2016-07-01 00:00:00.0; 6, p. 16-23.
PMID: 26949742
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Different Dietary Patterns And Reduction Of Lung Cancer Risk: A Large Case-control Study In The U.s
Authors: Tu H. , Heymach J.V. , Wen C.P. , Ye Y. , Pierzynski J.A. , Roth J.A. , Wu X. .
Source: Scientific Reports, 2016-05-27 00:00:00.0; 6, p. 26760.
PMID: 27230571
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Glycemic Index, Glycemic Load, And Lung Cancer Risk In Non-hispanic Whites
Authors: Melkonian S.C. , Daniel C.R. , Ye Y. , Pierzynski J.A. , Roth J.A. , Wu X. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2016 Mar; 25(3), p. 532-9.
PMID: 26944871
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Microrna-124 Suppresses Tumor Cell Proliferation And Invasion By Targeting Cd164 Signaling Pathway In Non-small Cell Lung Cancer
Authors: Lin J. , Xu K. , Wei J. , Heimberger A.B. , Roth J.A. , Ji L. .
Source: Journal Of Gene Therapy, 2016 Feb; 2(1), .
PMID: 27376157
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Telomere Length And Recurrence Risk After Curative Resection In Patients With Early-stage Non-small-cell Lung Cancer: A Prospective Cohort Study
Authors: Kim E.S. , Ye Y. , Vaporciyan A.A. , Xing J. , Huang M. , Gu J. , Roth J.A. , Lippman S.M. , Wu X. .
Source: Journal Of Thoracic Oncology : Official Publication Of The International Association For The Study Of Lung Cancer, 2015 Feb; 10(2), p. 302-8.
PMID: 25299235
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Exogenous Restoration Of Tusc2 Expression Induces Responsiveness To Erlotinib In Wildtype Epidermal Growth Factor Receptor (egfr) Lung Cancer Cells Through Context Specific Pathways Resulting In Enhanced Therapeutic Efficacy
Authors: Dai B. , Yan S. , Lara-Guerra H. , Kawashima H. , Sakai R. , Jayachandran G. , Majidi M. , Mehran R. , Wang J. , Bekele B.N. , et al. .
Source: Plos One, 2015; 10(6), p. e0123967.
PMID: 26053020
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Genetic Variations In Epigenetic Genes Are Predictors Of Recurrence In Stage I Or Ii Non-small Cell Lung Cancer Patients
Authors: Wagner,K.W. , Ye,Y. , Lin,J. , Vaporciyan,A.A. , Roth,J.A. , Wu,X. .
Source: Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research, 2012-01-15 00:00:00.0; 18(2), p. 585-92.
PMID: 22252258
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