Elise D Bowman

National Cancer Institute (USA), 베서스다, Maryland, United States

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Publications (104)688.21 Total impact

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  • Cancer Research 08/2015; 75(15 Supplement):LB-182-LB-182. DOI:10.1158/1538-7445.AM2015-LB-182 · 9.33 Impact Factor

  • Cancer Research 08/2015; 75(15 Supplement):935-935. DOI:10.1158/1538-7445.AM2015-935 · 9.33 Impact Factor
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    ABSTRACT: Up to 30% stage I lung cancer patients suffer recurrence within 5 years of curative surgery. We sought to improve existing protein-coding gene and microRNA expression prognostic classifiers by incorporating epigenetic biomarkers. Genome-wide screening of DNA methylation and pyrosequencing analysis of HOXA9 promoter methylation were performed in two independently collected cohorts of stage I lung adenocarcinoma. The prognostic value of HOXA9 promoter methylation alone and in combination with mRNA and miRNA biomarkers was assessed by Cox regression and Kaplan-Meier survival analysis in both cohorts. Promoters of genes marked by polycomb in embryonic stem cells were methylated de novo in tumors and identified patients with poor prognosis. The HOXA9 locus was methylated de novo in stage I tumors (p < 0.0005). High HOXA9 promoter methylation was associated with worse cancer-specific survival (hazard ratio [HR], 2.6; p = 0.02) and recurrence-free survival (HR, 3.0; p = 0.01), and identified high-risk patients in stratified analysis of stages IA and IB. Four protein-coding gene (XPO1, BRCA1, HIF1α, and DLC1), miR-21 expression, and HOXA9 promoter methylation were each independently associated with outcome (HR, 2.8; p = 0.002; HR, 2.3; p = 0.01; and HR, 2.4; p = 0.005, respectively), and when combined, identified high-risk, therapy naive, stage I patients (HR, 10.2; p = 3 × 10). All associations were confirmed in two independently collected cohorts. A prognostic classifier comprising three types of genomic and epigenomic data may help guide the postoperative management of stage I lung cancer patients at high risk of recurrence.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 07/2015; 10(7):1037-48. DOI:10.1097/JTO.0000000000000560 · 5.28 Impact Factor
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    ABSTRACT: The microRNA-34 family (miR-34a, -34b and -34c) have been reported to be tumor suppressor microRNAs (miRNAs) that are regulated by the TP53 and DNA hypermethylation. However, the expression, regulation, and prognostic value of the miR-34 family have not been systematically studied in colon cancer. To elucidate the roles of miR-34 family in colon carcinogenesis, miR-34a/b/c were measured in tumors and adjacent noncancerous tissues from 159 American and 113 Chinese colon cancer patients using quantitative RT-PCR, and we examined associations between miR-34a/b/c expression with TNM staging, cancer-specific mortality, TP53 mutation status and Affymetrix microarray data. All miR-34 family members were significantly increased in colon tumors, counter to the proposed tumor suppressor role for these miRNAs. Increased miR-34b/c were observed in more advanced tumors in two independent cohorts and increased expression of miR-34b/c was associated with poor cancer-specific mortality. While the expression of miR-34 family was not associated with TP53 mutation status, TP53 transcriptional activity was associated with miR-34a/b/ c expression that is consistent with the proposed regulation of miR-34a/b/c by TP53. To examine where the miR-34 family is expressed, the expression of miR-34 family was compared between epitheliums and stromal tissues using laser microdissection technique. The expression of miR-34b/c was increased significantly in stromal tissues, especially in cancer stroma, compared with epithelial tissue. In conclusion, increased miR-34b/c predominantly expressed in stromal tissues is associated with poor prognosis in colon cancer. MiR-34 may contribute to cancer-stromal interaction associated with colon cancer progression.
    PLoS ONE 04/2015; 10(4):e0124899. DOI:10.1371/journal.pone.0124899 · 3.23 Impact Factor
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    ABSTRACT: Although microRNAs (miRs) have been implicated in the pathogenesis of various human malignancies, limited information is available regarding mechanisms by which these noncoding RNAs contribute to initiation and progression of tobacco-induced esophageal cancers. In this study, array and quantitative reverse transcriptase–PCR techniques were used to examine miR expression in immortalized esophageal epithelia (IEE) and esophageal adenocarcinoma (EAC) cells cultured in normal media with or without cigarette smoke condensate (CSC). Under relevant exposure conditions, CSC significantly decreased miR-217 expression in these cells. Endogenous levels of miR-217 expression in cultured EAC cells (EACC)/primary EACs were significantly lower than those observed in IEE/ paired normal esophageal tissues. RNA crosslink immunoprecipitation, quantitative reverse transcriptase–PCR (qRT–PCR) and immunoblot experiments demonstrated direct interaction of miR-217 with kallikrein 7 (KLK7), encoding a putative oncogene not previously implicated in EAC. Repression of miR-217 correlated with increased levels of KLK7 in primary EACs, particularly those from smokers. Chromatin and methylated DNA immunoprecipitation experiments demonstrated that CSC-mediated repression of miR-217 coincided with DNMT3b-dependent hypermethylation and decreased occupancy of nuclear factor 1 within the miR-217 genomic locus. Deoxyazacytidine induced miR-217 expression and downregulated KLK7 in EACC; deoxyazacytidine also attenuated CSC-mediated miR-217 repression and upregulation of KLK7 in IEE and EACC. Overexpression of miR-217 significantly decreased, whereas overexpression of KLK7 increased proliferation, invasion and tumorigenicity of EACC. Collectively, these data demonstrate that epigenetic repression of miR-217 contributes to the pathogenesis of EAC via upregulation of KLK7 and suggest that restoration of miR-217 expression may be a novel treatment strategy for these malignancies.
    Oncogene 02/2015; 34(44). DOI:10.1038/onc.2015.10 · 8.46 Impact Factor
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    ABSTRACT: Global changes in gene expression accompany the development of cancer. Thus, inherited variants in microRNA binding sites are likely candidates for conferring inherited susceptibility. Using an in-silico approach, we compiled a comprehensive list of SNPs predicted to modulate microRNA binding in genes from several key lung cancer pathways. We then investigated whether these SNPs were associated with lung cancer risk in two independent populations. In general, SNPs in microRNA binding sites are rare. However, some allelic variation was observed. We found that rs1126579 in CXCR2 was associated with a reduced risk of lung cancer in both European American (ORTT vs. CC 0.56 [0.37 - 0.88]; P=0.008) and Japanese (ORTT vs. CC 0.62 [0.38 - 1.00]; P=0.049) populations. Further, we found that the SNP disrupted a novel binding site for miR-516a-3p, led to a moderate increase in CXCR2 mRNA and protein expression and increased MAPK signaling. Moreover, analysis of rs1126579 with serum levels of IL-8, its endogenous ligand, supported an interaction whereby rs1126579-T and high serum IL-8 conferred synergistic protection from lung cancer. Our findings demonstrate a function for a 3'UTR SNP in modulating CXCR2 expression, signaling and susceptibility to lung cancer. Copyright © 2014, American Association for Cancer Research.
    Cancer Research 12/2014; 75(3). DOI:10.1158/0008-5472.CAN-14-2101 · 9.33 Impact Factor
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    ABSTRACT: Lung cancer has a familial component which suggests a genetic contribution to its etiology. Given the strong evidence linking smoking with lung cancer, we studied miRNA-related loci in genes associated with smoking behavior. CHRNA, CHRNB gene families, CYP2A6 and DRD1 were mined for single nucleotide polymorphisms (SNPs) that fell within the seed region of miRNA binding sites and then tested for associations with risk in a three-stage validation approach. A 3'UTR SNP in DRD1 (Dopamine Receptor D1) was associated with a lower risk of lung cancer among individuals exposed to secondhand smoke during childhood (OR: 0.69; 0.60, 0.79; P<0.0001). This relationship was evident in both ever (OR: 0.74; 0.62, 0.88; P=0.001) and never smokers (OR 0.61; 0.47, 0.79; P<0.0001), European American (OR: 0.65; 0.53, 0.80; P<0.0001) and African American (OR: 0.73; 0.62, 0.88; P=0.001) populations. While much remains undefined about the long-term risks associated with exposure to secondhand smoke and heterogeneity between individuals in regard to their susceptibility to the effects of secondhand smoke, our data show an interaction between a SNP in the 3'UTR of DRD1 and exposure to secondhand smoke during childhood. Further work is needed to explore the mechanistic underpinnings of this SNP and the nature of the interaction between DRD1 and exposure to secondhand smoke during childhood.
    Cancer Prevention Research 10/2014; 7(12). DOI:10.1158/1940-6207.CAPR-14-0158 · 4.44 Impact Factor

  • Cancer Research 10/2014; 74(19 Supplement):2156-2156. DOI:10.1158/1538-7445.AM2014-2156 · 9.33 Impact Factor
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    ABSTRACT: Background and aims Patients with inflammatory bowel disease (IBD) have a higher risk of developing colorectal cancer than the general population. Genome-wide association studies have identified and replicated several loci associated with risk of IBD; however, it is currently unknown whether these loci are also associated with colon cancer risk. Methods We selected 15 validated SNPs associated with risk of either Crohn's disease, ulcerative colitis, or both in previous GWAS and tested whether these loci were also associated with colon cancer risk in a two-stage study design. Results We found that rs744166 in STAT3 was associated with colon cancer risk in two studies; however, the direction of the observation was reversed in TP53 mutant tumors possibly due to a nullification of the effect by mutant p53. The SNP, which lies within intron 1 of the STAT3 gene, was associated with lower expression of STAT3 mRNA in TP53 wild-type, but not mutant, tumors. Conclusions These data suggest that the STAT3 locus is associated with both IBD and cancer. Further understanding the function of this variant in relation to TP53 could possibly explain the role of this gene in autoimmunity and cancer. Furthermore, an analysis of this locus, specifically in a population with IBD, could help to resolve the relationship between this SNP and cancer.
    Cancer Epidemiology 10/2014; 38(5). DOI:10.1016/j.canep.2014.07.003 · 2.71 Impact Factor

  • Cancer Research 05/2014; 73(19 Supplement):A47-A47. DOI:10.1158/1538-7445.FBCR13-A47 · 9.33 Impact Factor
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    ABSTRACT: Lung cancer remains the most common cause of cancer deaths worldwide, yet there is currently a lack of diagnostic noninvasive biomarkers that could guide treatment decisions. Small molecules (<1500 Da) were measured in urine collected from 469 lung cancer patients and 536 population controls using unbiased liquid chromatography-mass spectrometry. Clinical putative diagnostic and prognostic biomarkers were validated by quantitation and normalized to creatinine levels at two different time points and further validated in an independent sample set, which comprises 80 cases and 78 population controls, with similar demographic and clinical characteristics when compared to the training set. Creatine riboside (IUPAC name: 2-{2-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)-oxolan-2-yl]-1-methylcarbamimidamido}acetic acid), a novel molecule identified in this study, and N-acetylneuraminic acid (NANA), were each significantly (P <0.00001) elevated in non-small cell lung cancer (NSCLC) and associated with worse prognosis (hazard ratio (HR) =1.81 [P =0.0002], and 1.54 [P =0.025], respectively). Creatine riboside was the strongest classifier of lung cancer status in all and stage I-II cases, important for early detection, and also associated with worse prognosis in stage I-II lung cancer (HR =1.71, P =0.048). All measurements were highly reproducible with intraclass correlation coefficients ranging from 0.82 - 0.99. Both metabolites were significantly (P <0.03) enriched in tumor tissue compared to adjacent non-tumor tissue (N =48), thus revealing their direct association with tumor metabolism. Creatine riboside and NANA may be robust urinary clinical metabolomic markers that are elevated in tumor tissue and associated with early lung cancer diagnosis and worse prognosis.
    Cancer Research 04/2014; 74(12). DOI:10.1158/0008-5472.CAN-14-0109 · 9.33 Impact Factor
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    ABSTRACT: Colon cancer (CC) is a leading cause of cancer mortality. Novel biomarkers are needed to identify CC patients at high risk of recurrence and those who may benefit from therapeutic intervention. The aim of this study is to investigate if miR-21 expression from RNA isolated from formalin-fixed paraffin-embedded (FFPE) tissue sections is associated with prognosis and therapeutic outcome for patients with CC. The expression of miR-21 was measured by quantitative reverse transcriptase-polymerase chain reaction in a Japanese cohort (stage I-IV, n = 156) and a German cohort (stage II, n = 145). High miR-21 expression in tumors was associated with poor survival in both the stage II/III Japanese (P = 0.0008) and stage II German (P = 0.047) cohorts. These associations were independent of other clinical covariates in multivariable models. Receipt of adjuvant chemotherapy was not beneficial in patients with high miR-21 in either cohort. In the Japanese cohort, high miR-21 expression was significantly associated with poor therapeutic outcome (P = 0.0001) and adjuvant therapy was associated with improved survival in patients with low miR-21 (P = 0.001). These results suggest that miR-21 is a promising biomarker to identify patients with poor prognosis and can be accurately measured in FFPE tissues. The expression of miR-21 may also identify patients who will benefit from adjuvant chemotherapy. © 2013 Wiley Periodicals, Inc.
    International Journal of Cancer 04/2014; 134(8). DOI:10.1002/ijc.28522 · 5.09 Impact Factor
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    ABSTRACT: There are no robust noninvasive methods for colorectal cancer screening and diagnosis. Metabolomic and gene expression analyses of urine and tissue samples from mice and humans were used to identify markers of colorectal carcinogenesis. Mass spectrometry-based metabolomic analyses of urine and tissues from wild-type C57BL/6J and Apc(Min/+) mice, as well as from mice with azoxymethane-induced tumors, was employed in tandem with gene expression analysis. Metabolomics profiles were also determined on colon tumor and adjacent non-tumor tissues from 39 patients. The effects of β-catenin activity on metabolic profiles were assessed in mice with colon-specific disruption of Apc. Thirteen markers were found in urine associated with development of colorectal tumors in Apc(Min/+) mice. Metabolites related to polyamine metabolism, nucleic acid metabolism, and methylation, identified tumor-bearing mice with 100% accuracy, and also accurately identified mice with polyps. Changes in gene expression in tumor samples from mice reflected the observed changes in metabolic products detected in urine; similar changes were observed in mice with azoxymethane-induced tumors and mice with colon-specific activation of β-catenin. The metabolic alterations indicated by markers in urine therefore appear to occur during early stages of tumorigenesis, when cancer cells are proliferating. In tissues from patients, tumors had stage-dependent increases in 12 metabolites associated with the same metabolic pathways identified in mice (including amino acid metabolism and polyamine metabolism). Ten metabolites that were increased in tumor tissues, compared with non-tumor tissues (proline, threonine, glutamic acid, arginine, N1-acetylspermidine, xanthine, uracil, betaine, symmetric dimethylarginine, and asymmetric-dimethylarginine), were also increased in urine from tumor-bearing mice. Gene expression and metabolomic profiles of urine and tissue samples from mice with colorectal tumors and of colorectal tumor samples from patients revealed metabolites associated with specific metabolic changes that are indicative of early-stage tumor development. These urine and tissue markers might be used in early detection of colorectal cancer.
    Gastroenterology 01/2014; 146(5). DOI:10.1053/j.gastro.2014.01.017 · 16.72 Impact Factor

  • Cancer Research 08/2013; 73(8 Supplement):1901-1901. DOI:10.1158/1538-7445.AM2013-1901 · 9.33 Impact Factor
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    ABSTRACT: Prognostic tests for early stage lung cancer patients may provide needed guidance on postoperative surveillance and therapeutic decisions. We used a novel strategy to develop and validate a prognostic classifier for early stage lung cancer. Specifically, we focused on 42 genes with roles in lung cancer or cancer prognosis. Expression of these biologically relevant genes and their association with relapse-free survival were evaluated using microarray data from 148 stage I lung adenocarcinoma patients. Seven genes associated with relapse-free survival were further examined by quantitative RT-PCR in 291 lung adenocarcinoma tissues from Japan, the United States and Norway. Only BRCA1, HIF1A, DLC1, and XPO1 were each significantly associated with prognosis in the Japan and US/Norway cohorts. A Cox regression-based classifier was developed using these four genes on the Japan cohort and validated in stage I lung adenocarcinoma from the US/Norway cohort and three publically available lung adenocarcinoma expression profiling datasets. The results suggests that the classifier is robust across ethnically and geographically diverse populations regardless of the technology used to measure gene expression. We evaluated the combination of the four-gene classifier with microRNA miR-21 (MIR21) expression and found that the combination improved associations with prognosis, which were significant in stratified analyses on stage IA and stage IB patients. Thus, the four coding gene classifier, alone or with miR-21 expression, may provide a clinically useful tool to identify high risk patients and guide recommendations regarding adjuvant therapy and postoperative surveillance of stage I lung adenocarcinoma patients.
    Cancer Research 05/2013; 73(13). DOI:10.1158/0008-5472.CAN-13-0031 · 9.33 Impact Factor

  • Cancer Research 04/2013; 73(8 Supplement):4581-4581. DOI:10.1158/1538-7445.AM2013-4581 · 9.33 Impact Factor
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    ABSTRACT: Conflicting reports exist regarding the contribution of SNP309 in MDM2 to cancer risk. Recently, SNP285 was shown to act as an antagonist to SNP309 by overriding the effect of SNP309 on SP1-mediated transcription. Moreover, SNP285 modified the relationship between SNP309 and risk of breast, ovarian and endometrial cancer. We assessed whether SNP285 confounded the effect of SNP309 in lung cancer in a cohort of 720 controls and 556 cases. Our cohort included both Caucasians and African Americans. Neither SNP309 nor SNP285 was associated with lung cancer risk or survival. In addition, removal of individuals who carried the variant C allele of SNP285 did not modify the association between SNP309 with either lung cancer risk or survival. Although an effect of SNP285 has been demonstrated in breast, ovarian and endometrial cancer, our findings do not support a role for this SNP in lung cancer and raise the possibility that the effect of SNP285 is restricted to cancers in women.
    International Journal of Cancer 12/2012; 131(11):2710-6. DOI:10.1002/ijc.27573 · 5.09 Impact Factor
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    ABSTRACT: Cellular senescence can be a functional barrier to carcinogenesis. We hypothesized that inflammation modulates carcinogenesis through senescence and DNA damage response (DDR). We examined the association between senescence and DDR with macrophage levels in inflammatory bowel disease (IBD). In vitro experiments tested the ability of macrophages to induce senescence in primary cells. Inflammation modulating microRNAs were identified in senescence colon tissue for further investigation. Quantitative immunohistochemistry identified protein expression by colon cell type. Increased cellular senescence (HP1γ; P = 0.01) or DDR (γH2A.X; P = 0.031, phospho-Chk2, P = 0.014) was associated with high macrophage infiltration in UC. Co-culture with macrophages (ANA-1) induced senescence in >80% of primary cells (fibroblasts MRC5, WI38), illustrating that macrophages induce senescence. Interestingly, macrophage-induced senescence was partly dependent on nitric oxide synthase, and clinically relevant NO• levels alone induced senescence. NO• induced DDR in vitro, as detected by immunofluorescence. In contrast to UC, we noted in Crohn's disease (CD) that senescence (HP1γ; P<0.001) and DDR (γH2A.X; P<0.05, phospho-Chk2; P<0.001) were higher, and macrophages were not associated with senescence. We hypothesize that nitric oxide may modulate senescence in CD; epithelial cells of CD had higher levels of NOS2 expression than in UC (P = 0.001). Microarrays and quantitative-PCR identified miR-21 expression associated with macrophage infiltration and NOS2 expression. Senescence was observed in IBD with senescence-associated β-galactosidase and HP1γ. Macrophages were associated with senescence and DDR in UC, and in vitro experiments with primary human cells showed that macrophages induce senescence, partly through NO•, and that NO• can induce DDR associated with senescence. Future experiments will investigate the role of NO• and miR-21 in senescence. This is the first study to implicate macrophages and nitrosative stress in a direct effect on senescence and DDR, which is relevant to many diseases of inflammation, cancer, and aging.
    PLoS ONE 09/2012; 7(9):e44156. DOI:10.1371/journal.pone.0044156 · 3.23 Impact Factor
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    ABSTRACT: Through their roles in tissue remodeling, variants in the genes that encode alpha1-antitrypsin (AAT) and neutrophil elastase (NE) were hypothesized to be associated with the risk of both chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC). Cases with prevalent COPD (n=145), incident NSCLC (n=203) or prevalent COPD plus NSCLC (n=118) were compared to disease-free controls (n=317), to assess two functional polymorphisms in serpin peptidase inhibitor, clade A, member 1 (SERPINA1), which encodes AAT, and eleven tagging polymorphisms in and around elastase 2 (ELA2), which encodes NE. All analyses were stratified by race. Among African-Americans, the less efficient SERPINA1 variant appeared to be associated with increased risk of prevalent COPD but only in the presence of NSCLC (odds ratio=7.39; 95% confidence interval=1.03-53.21) and not after correcting for multiple comparisons. Variations in SERPINA1 and ELA2 were not consistently or strongly associated with the risk of either COPD or NSCLC in either race.
    Anticancer research 09/2012; 32(9):3923-8. · 1.83 Impact Factor

Publication Stats

7k Citations
688.21 Total Impact Points


  • 1990-2015
    • National Cancer Institute (USA)
      • • Laboratory of Human Carcinogenesis
      • • Genetic Epidemiology
      • • Cancer Etiology Branch (CEB)
      베서스다, Maryland, United States
  • 2008-2014
    • NCI-Frederick
      Фредерик, Maryland, United States
  • 1994-2014
    • National Institutes of Health
      • Laboratory of Human Carcinogenesis
      베서스다, Maryland, United States
  • 2005
    • Uniformed Services University of the Health Sciences
      Maryland, United States
  • 2001
    • Georgetown University
      Washington, Washington, D.C., United States
  • 2000
    • Cornell University
      Итак, New York, United States
  • 1998-1999
    • Fox Chase Cancer Center
      Filadelfia, Pennsylvania, United States
  • 1996
    • University at Buffalo, The State University of New York
      • Department of Social and Preventive Medicine
      Buffalo, NY, United States
  • 1993
    • Lawrence Livermore National Laboratory
      Livermore, California, United States