表调节蛋白过表达与肾透明细胞癌患者预后的相关性及机制

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Correlation and mechanism of EREG overexpression and prognosis of patients with renal clear cell carcinoma

ZHAO Jinguo1 ，ZHANG Bin2 ，JI Yaoxuan²，YU Lei1

（1.Department of Urology，Xijing Hospital，2.Department of Aviation Physiology，Department of Aerospace

Medicine，Air Force Medical University，Xi'an 710032，China）

ABSTRACT：ObjectiveTo explore therole and mechanism of epiregulin （EREG）in clearcell renal cellcarcinoma （ccRCC），andto find biomarkers and therapeutic targets for ccRCC.MethodsBased on the data from The Cancer Genome Atlas（TCGA）and Genotype-Tissue Expression（GTEx）databases，the corelation between the expression level of EREG in ccRCCtissues and theclinicalstaging and survival of ccRCC patients was analyzed.The samplesof 6ccRCCcases treated in the SecondAfilited Hospitalof theAirForce Medical Universitywerecollected.Theexpressionof EREGwas confirmed with immunohistochemistryandquantitativereal-time polymerase chain reaction（q-PCR）．Theeffectsof EREG overexpressonon theproliferation，cellcycle and apoptosisof ACHN celswere verified with CCK-8and flow cytometry. Finall，the expresions of EREG，epidermal growth factor receptor（EGFR）and the downstream pathway proteins were detected with Western blotting.ResultsBased on the databases，it was found that theexpressonofEREG inccRCC samples was higherthanthatinadjacenttissues，andthere wasapositivecorelationwithteclinicalstage.Survivalanalysis showed that highexpresion of EREG was arisk factor affecting the prognosis.The resultsof immunohistochemical staining and qPCR revealed that EREG was highly expressed in ccRCC. Flow cytometry showed that EREG overexpresson promoted the proliferationofCHNcels，enanced cellcycle，and inhibited apoptosis.Inaddition，WesternblotingsuggestedthatEREG promoted the expressions of EREG，EGFR and the downstream proteins.ConclusionThe expression of EREG is sociated withthe prognosis of ccRCCpatients.In vitrocellexperiments have shown thatitcan promote the proliferationof ccRCCcels andinhibit theirapoptosis，thereby leading totheprogresionofccRCC.Itcanserve asapotentialbiomarkerforprognosis prediction and a drug development target for ccRCC patients.

KEY WORDS：clear cel renal cellcarcinoma； epiregulin； prognostic prediction； biomarker;proliferation；apoptosis

摘要：目的探索表调节蛋白（EREG）在肾透明细胞癌（ccRCC）中的作用及其机制，为ccRCC 寻找生物标志物及治疗靶点。（剩余12993字）