NOTCH1, HIF1A and Other Cancer-Related Proteins in Lung Tissue from Uranium Miners—Variation by Occupational Exposure and Subtype of Lung Cancer 英文参考文献.docVIP
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NOTCH1, HIF1A and Other Cancer-Related Proteins in Lung Tissue from Uranium Miners—Variation by Occupational Exposure and Subtype of Lung Cancer 英文参考文献
NOTCH1,HIF1AandOtherCancer-RelatedProteinsin
LungTissuefromUraniumMiners—Variationby
OccupationalExposureandSubtypeofLungCancer
BeatePesch1*,SwaantjeCasjens1,IngoStricker2,DanielaWesterwick2,DirkTaeger1,SylviaRabstein1,
ThorstenWiethege1,AndreaTannapfel2,ThomasBru¨ning1,GeorgJohnen1
1Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany,
2InstituteofPathology,RuhrUniversityBochum,Bochum,Germany
Abstract
Background: Radon and arsenic are established pulmonary carcinogens. We investigated the association of cumulative
exposuretothesecarcinogenswithNOTCH1,HIF1Aandothercancer-specificproteinsinlungtissuefromuraniumminers.
Methodology/Principal Findings: Paraffin-embedded tissue of 147 miners was randomly selected from an autopsy
repository by type of lung tissue, comprising adenocarcinoma (AdCa), squamous cell carcinoma (SqCC), small cell lung
cancer (SCLC),andcancer-free tissue.Withineachstratum, weadditionallystratifiedby loworhigh levelofexposureto
radonorarsenic.Lifetimeexposuretoradonandarsenicwasestimatedusingaquantitativejob-exposurematrixdeveloped
for uranium mining. For 22 cancer-related proteins, immunohistochemical scores were calculated from the intensity and
percentageofstainedcells.Weexploredtheassociationsofthesescoreswithcumulativeexposuretoradonandarsenic
withSpearmanrankcorrelationcoefficients(rs).Occupationalexposurewasassociatedwithanup-regulationofNOTCH1
(radon rs=0.18, 95% CI 0.02–0.33; arsenic: rs=0.23, 95% CI 0.07–0.38). Moreover, we investigated whether these cancer-
relatedproteinscanclassifylungcancerusingsupervisedandunsupervisedclassification.MUC1classifiedlungcancerfrom
cancer-freetissuewithafailurerateof2.1%.Atwo-proteinsignaturediscriminatedSCLC(HIF1Alow),AdCa(NKX2-1high),
andSqCC(NKX2-1low)withafailurerateof8.4%.
Conclusions/Significance:Theseresultssuggestthattheradiation-sensitiveproteinNOTCH1canbeup-regulatedinlung
tissue from ur
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