Genome-Wide Association Study of Prognosis in Advanced Non–Small Cell Lung Cancer Patients Receiving Platinum-Based Chemotherapy

Hu, Lingmin; Wu, Chen; Zhao, Xingyu; Heist, Rebecca S.; Li, Su; Zhao, Yang; Han, Baohui; Cao, Shougen; Chu, Minjie; Dai, Juncheng; Dong, Jing; Shu, Yongqian; Xu, Lin; Chen, Yijiang; Wang, Yi; Lu, Feng; Jiang, Yue; Yu, Dianke; Chen, Hongyan; Tan, Wen; Ma, Hongxia; Chen, Jiaping; Jin, Guangfu; Wu, Tangchun; Lu, Daru; Christiani, David C.; Lin, Dong; Hu, Zhibin; Shen, Hongbing

doi:10.1158/1078-0432.ccr-12-1202

Cited by 55 publications

(44 citation statements)

References 41 publications

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“…Thus, the most advanced high throughput technologies have enabled the exploration of the cellular traits associated with increased resistance to CDDP at multiple levels. For instance, the genomic and epigenetic features associated with the loss of CDDP sensitivity have been thoroughly examined trough the search for Small Nucleotide Polymorphism (SNP) associated with CDDP resistance [1][2][3][4] or by exome sequencing. 5 Gene expression programs associated with CDDP resistance have also been intensively scrutinized by cDNA microarrays analysis or exploring alternative levels of gene expression regulation such as those mediated by microRNAs or long non-coding RNAs.…”

Section: Reportmentioning

confidence: 99%

Translational regulation of the mRNA encoding the ubiquitin peptidase USP1 involved in the DNA damage response as a determinant of Cisplatin resistance

et al. 2016

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(2016) Cisplatin (cis-diaminedichloroplatin (II), CDDP) is part of the standard therapy for a number of solid tumors including Non-Small-Cell Lung Cancer (NSCLC). The initial response observed is in most cases only transient and tumors quickly become refractory to the drug. Tumor cell resistance to CDDP relies on multiple mechanisms, some of which still remain unknown. In search for such mechanisms, we examined the impact of CDDP on mRNA translation in a sensitive and in a matched resistant NSCLC cell line. We identified a set of genes whose mRNAs are differentially translated in CDDP resistant vs. sensitive cells. The translation of the mRNA encoding the Ubiquitin-Specific Peptidase 1 (USP1), a Ubiquitin peptidase with important function in multiple DNA repair pathways, is inhibited by CDDP exposure in the sensitive cells, but not in the resistant cells. This lack of down-regulation of USP1 expression at the translational level plays a primary role in CDDP resistance since inhibition of USP1 expression or activity by siRNA or the small molecule inhibitor ML323, respectively is sufficient to re-sensitize resistant cells to CDDP. We involved the USP1 mRNA translation as a major mechanism of CDDP resistance in NSCLC cells and suggest that USP1 could be evaluated as a candidate predictive marker and as a therapeutic target to overcome CDDP resistance. More generally, our results indicate that analysis of gene expression at the level of mRNA translation is a useful approach to identify new determinants of CDDP resistance.

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Section: Reportmentioning

confidence: 99%

Translational regulation of the mRNA encoding the ubiquitin peptidase USP1 involved in the DNA damage response as a determinant of Cisplatin resistance

et al. 2016

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“…Among these five SNPs, two SNPs, rs7629386 in CTNNB1 and rs3850370 in SNW1-ALKBH1-NRXN3, were further replicated in a Caucasian population (32). One of the strengths of this study is that the suggestive associated SNPs were not only validated in an independent sample from the Chinese population but also in another sample set from the Caucasian population.…”

Section: Lung Cancermentioning

confidence: 87%

Genome-Wide Association Study: A Useful Tool to Identify Common Genetic Variants Associated with Drug Toxicity and Efficacy in Cancer Pharmacogenomics

Low

Takahashi

Mushiroda

et al. 2014

Clinical Cancer Research

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In recent years, the utilization of genome-wide association study (GWAS) has proved to be a beneficial method to identify novel common genetic variations not only for disease susceptibility but also for drug efficacy and drug-induced toxicity, creating a field of pharmacogenomics studies. In addition, the findings from GWAS also generate new biologic hypotheses that could improve the understanding of pathophysiology for disease or the mechanism of drug-induced toxicity. This review highlights the implications of GWAS that have been published to date and discusses the successes as well as challenges of using GWAS in cancer pharmacogenomics. The aim of pharmacogenomics is to realize the vision of personalized medicine; it is hoped that through GWAS, novel common genetic variations could be identified to predict clinical outcome and/or toxicity in cancer therapies that subsequently could be implemented to improve the quality of lives of patients with cancer. Nevertheless, given the complexity of cancer therapies, underpowered studies, and large heterogeneity of study designs, collaborative efforts are needed to validate these findings and overcome the limitations of GWA studies before clinical implementation.

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“…Evidences revealed that patients with lung cancer with similar stages or histologic classifications have dramatically different responses to anticancer therapies and distinct survival outcomes, likely due to heterogeneity of gene/protein expression profiles (3). Established methods for predicting prognosis include the tumor, node, and metastasis (TNM) staging system; however, accumulating studies indicated that genetic biomarkers might play a vital role in cancer prognosis, according to their influences on cancer progression and treatment efficiency (4,5). Therefore, seeking distinctive molecular biomarkers and genetic variants of the key genes involved tumor initiation and progression may promote improving survival outcomes for human cancers.…”

Section: Introductionmentioning

confidence: 99%

Sequence Variation in Mature MicroRNA-499 Confers Unfavorable Prognosis of Lung Cancer Patients Treated with Platinum-Based Chemotherapy

Qiu

Yang

Ling

et al. 2015

Clinical Cancer Research

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Purpose: This study was implemented to investigate the associations between SNP in mature microRNA (miRNA) sequence and lung cancer prognosis and to verify the function of those SNP.Experimental Design: Eight SNPs (rs3746444T>C in hsa-mir-499, rs4919510C>G in hsa-mir-608, rs13299349G>A in hsa-mir-3152, rs12220909G>C in hsa-mir-4293, rs2168518G>A in hsamir-4513, rs8078913T>C in hsa-mir-4520a, rs11237828T>C in hsa-mir-5579, and rs9295535T>C in hsa-mir-5689) were analyzed in a southern Chinese population with 576 patients with lung cancer, and the significant results were validated in two additional cohorts of 346 and 368 patients, respectively. A series of experiments were performed to evaluate the relevancies of those potentially functional SNPs.Results: We found that the microRNA-499 rs3746444T>C polymorphism exhibited a consistently poor prognosis for patients with lung cancer in the discovery set [HR, 1.24; 95% confidence interval (CI), 1.02-1.49; P ¼ 0.028], in the validation set I (HR, 1.31; 95% CI, 1.01-1.71; P ¼ 0.048) and in the validation set II (HR, 1.45; 95% CI, 1.12-1.86; P ¼ 0.004). The adverse effect of CT/CC variants was more remarkable in patients receiving platinum-based chemotherapy. Further functional assays demonstrated that the rs3746444C variant allele influences the expression of several cancer-related genes and affects lung cancer cells' proliferation and tumor growth in vivo and in vitro via the cisplatinum resistance.Conclusion: Our findings suggested that the rs3746444T>C polymorphism in mature miR-499 sequence could contribute to poor prognosis by modulating cancer-related genes' expression and thus involve tumorigenesis and anti-chemotherapy, which may be a useful biomarker to predict lung cancer patients' prognosis.

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Genome-Wide Association Study of Prognosis in Advanced Non–Small Cell Lung Cancer Patients Receiving Platinum-Based Chemotherapy

Cited by 55 publications

References 41 publications

Translational regulation of the mRNA encoding the ubiquitin peptidase USP1 involved in the DNA damage response as a determinant of Cisplatin resistance

Translational regulation of the mRNA encoding the ubiquitin peptidase USP1 involved in the DNA damage response as a determinant of Cisplatin resistance

Genome-Wide Association Study: A Useful Tool to Identify Common Genetic Variants Associated with Drug Toxicity and Efficacy in Cancer Pharmacogenomics

Sequence Variation in Mature MicroRNA-499 Confers Unfavorable Prognosis of Lung Cancer Patients Treated with Platinum-Based Chemotherapy

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