Molecular Analysis of Plasma DNA for the Early Detection of Lung Cancer by Quantitative Methylation-Specific PCR

Ostrow, Kimberly Laskie; Hoque, Mohammad O.; Loyo, Myriam; Brait, Mariana; Greenberg, Alissa K.; Siegfried, Jill M.; Grandis, Jennifer R.; Davis, Autumn Gaither; Bigbee, William L.; Rom, William N.; Sidransky, David

doi:10.1158/1078-0432.ccr-09-3304

Cited by 100 publications

(79 citation statements)

References 45 publications

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“…The altered expression of KIF1A and other kinesin superfamily genes has been reported in a variety of human cancers including breast, glioblastoma, and prostate cancer (27)(28)(29). A recent study reported that KIF1A showed significant differences in plasma DNA methylation between control and patient samples in lung cancer and suggested a significant potential of molecular detection approaches (30). COCH is a cell adhesion molecule (31) that maps to human chromosome 14q11.…”

Section: Discussionmentioning

confidence: 99%

Three-gene signature predicts disease progression of non-muscle invasive bladder cancer

Jeong

Cho

et al. 2011

Oncology Letters

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Abstract.The clinical grades and staging methods currently employed for bladder cancer (BC) are inadequate for assessing treatment outcomes for non-muscle invasive bladder cancer (NMIBC). We have developed a clinically applicable quantitative real-time PCR (qPCR) gene signature to predict the progression of NMIBC. Three genes not previously described for BC were selected from our published progression-related gene classifier data set. Data were drawn from a previous study population and from new cases. Primary NMIBC tissue specimens (n=193) were analyzed by qPCR. Risk scores were then used to rank specimens into high-and low-risk signature groups based on their gene expression. The Kaplan-Meier method and a multivariate Cox regression model were used to identify the prognostic value of the three-gene signature for both recurrence and progression. The Kaplan-Meier estimates revealed significant differences in time-to-recurrence and progression between low-and high-risk signatures (log-rank test, p=0.011 and p<0.001, respectively). The multivariate Cox regression analysis showed that the three-gene risk signature is an independent predictor of bladder tumor progression (hazard ratio, 4.268; 95% CI, 1.542-11.814; p=0.005). In conclusion, our three-gene signature was found to be closely associated with progression among patients with NMIBC. IntroductionBladder cancer (BC), the incidence and mortality of which increases directly with age, is a heterogeneous disease that affects approxi mately 68,000 people in the United States annually (1). In Korea, BC is the second most common urological malignancy and is about five times more common in male as compared to female individuals (2). Patients diagnosed with non-muscle invasive bladder cancers (NMIBC) may have indolent, albeit recurrent, disease. However, NMIBC patients are required to receive frequent cystourethroscopy, which is inconvenient for patients. Additionally, they may experience progression to muscle invasive bladder cancer (MIBC), which potentially has a narrow window-of-cure and requires aggressive treatment (3). Therefore, predicting the course of the disease is of great value to both patients and urologists, in order for adequate management of NMIBC to occur. For example, early radical cystectomy has a superior 5-year survival rate compared to bladder-sparing surgery (4). The development of accurate and reliable biological markers would be useful for assessing aggressiveness and for predicting the prognosis of NMIBC.Previously, we undertook a microarray analysis of specimens derived from 103 primary NMIBC patients and identified an eight-gene progression-related gene classifier (5). Although there have been numerous attempts to establish prognostic markers for NMIBC (3,(6)(7)(8)

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Section: Discussionmentioning

confidence: 99%

Three-gene signature predicts disease progression of non-muscle invasive bladder cancer

Jeong

Cho

et al. 2011

Oncology Letters

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“…Its location at 3p21.1 puts it in a category of tumor suppressor genes that are associated with the development of many cancers (12). Highly aggressive breast cancer cells frequently exhibit genomic loss of the NISCH locus (12), whereas the NISCH promoter is hypermethylated in lung cancers (13). Nischarin mRNA and protein expression is high in stage 0 human breast specimens but reduced in stage I-IV breast cancer specimens (12).…”

Section: Discovery Of Nischarinmentioning

confidence: 99%

Breast Cancer Tumor Suppressors: A Special Emphasis on Novel Protein Nischarin

Maziveyi

Alahari

2015

Cancer Research

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Tumor suppressor genes regulate cell growth and prevent spontaneous proliferation that could lead to aberrant tissue function. Deletions and mutations of these genes typically lead to progression through the cell-cycle checkpoints, as well as increased cell migration. Studies of these proteins are important as they may provide potential treatments for breast cancers. In this review, we discuss a comprehensive overview on Nischarin, a novel protein discovered by our laboratory. Nischarin, or imidazoline receptor antisera-selected protein, is a protein involved in a vast number of cellular processes, including neuronal protection and hypotension. The NISCH promoter experiences hypermethylation in several cancers, whereas some highly aggressive breast cancer cells exhibit genomic loss of the NISCH locus. Furthermore, we discuss data illustrating a novel role of Nischarin as a tumor suppressor in breast cancer. Analysis of this new paradigm may shed light on various clinical questions. Finally, the therapeutic potential of Nischarin is discussed.

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“…69 Both global and gene-specifi c epigenetic changes are being tested as noninvasive biomarkers for early detection and prognosis of lung cancer. 70,71 Systematic examination of the "methylome" can be used to further subclassify molecular and clinically distinct subgroups of lung cancer and to potentially guide therapeutic decisions. Brock et al 72 examined the prognostic value of methylation patterns for seven genes ( p16 , MGMT , DAPK , RASSF1A , CDH13 , ASC , and APC ) in the setting of resected stage 1 NSCLC.…”

Section: Methylationmentioning

confidence: 99%

Molecular Biology of Lung Cancer

Nana‐Sinkam

Powell

2013

Chest

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Lung cancer is the leading cause of cancer death in the United States, with 157,000 deaths annually, and in the world, with 1,375,000 deaths annually. 2 The overall 5-year survival for lung cancer remains at 16%, which is signifi cantly lower than the mortality rate for other common cancers, including colon, breast, and prostate cancer. The discrepancy in the mortality rate of lung cancer compared with other cancers has several explanations. First, lung cancers are typically detected at an advanced stage. The anticipated implementation of population-based screening for lung cancer is expected to decrease mortality. Second, compared with the other common cancers that share adenocarcinoma as the histology, lung cancer is heterogenous histologically and biologically. Until recently, lung cancer was treated as a homogenous disease with all nonsmall cell lung cancers (NSCLCs) treated identically, solely on the basis of clinical stage. Based on bench and clinical research, the treatment of lung cancer has been refi ned, with treatments allocated according to histology and specifi c molecular features. For example, targeting mutations such as epidermal growth factor receptor (EGFR) with tyrosine kinase inhibitors (TKIs) has been particularly successful as a treatment modality, demonstrating response rates in patients with EGFR-mutated adenocarcinoma that are significantly higher than those for conventional chemotherapy. However, the development of new targeted therapies is, in part, highly dependent on an improved understanding of the molecular underpinnings of tumor initiation and progression, knowledge of the role of molecular aberrations in disease progression, Based on recent bench and clinical research, the treatment of lung cancer has been refi ned, with treatments allocated according to histology and specifi c molecular features. For example, targeting mutations such as epidermal growth factor receptor (EGFR) with tyrosine kinase inhibitors has been particularly successful as a treatment modality, demonstrating response rates in selected patients with adenocarcinoma tumors harboring EGFR mutations that are signifi cantly higher than those for conventional chemotherapy. However, the development of new targeted therapies is, in part, highly dependent on an improved understanding of the molecular underpinnings of tumor initiation and progression, knowledge of the role of molecular aberrations in disease progression, and the development of highly reproducible platforms for high-throughput biomarker discovery and testing. In this article, we review clinically relevant research directed toward understanding the biology of lung cancer. The clinical purposes of this research are (1) to identify susceptibility variants and fi eld molecular alterations that will promote the early detection of tumors and (2) to identify tumor molecular alterations that serve as therapeutic targets, prognostic biomarkers, or predictors of tumor response. We focus on research developments in the understanding of lung cancer somatic DNA mutat...

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Molecular Analysis of Plasma DNA for the Early Detection of Lung Cancer by Quantitative Methylation-Specific PCR

Cited by 100 publications

References 45 publications

Three-gene signature predicts disease progression of non-muscle invasive bladder cancer

Three-gene signature predicts disease progression of non-muscle invasive bladder cancer

Breast Cancer Tumor Suppressors: A Special Emphasis on Novel Protein Nischarin

Molecular Biology of Lung Cancer

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