Study On The Pathogenesis Of The Hormone Receptor In The Endometrioid Adenocarcinoma

Objective:Study on the profile of gene expression association with the distinct estrogen and progestogen receptor in endometrioid adenocarcinoma.so as to reveal the role of the estrogen and progestogen receptor in the pathogenesis of endometrioid adenocarcinoma and provid a special targeted therapy in rationale.Methods:(1)By drawing the RNA from the endometrioid adenocarcinoma with estrogen receptor and progestogen receptor all positive(ER+)(PR+),estrogen receptor and progestogen receptor all negetive(ER-)(PR-),estrogen receptor positive and progestogen receptor negetive(ER+)(PR-),and normal endometrium,respectively, reversetranscription RNA to cDNA and hybridization with 17kcDNA human gene chip,screen the gene ratio equal 2 or higher than 2 and ratio eqeal -2 or lower than -2 as the difference expression genes.(2) Analysis the genetic expression and the apoptosis signal pathway and the related gene in the distincted expression of ER and PR in endometrioid adenocarcinoma by bioinformatics.(3) Verification the genes by reverse transcriptase PCR and immunohisochemistry.Results:(1) There differential expression genes were 1653,1756, 2215 strips when the(ER+)(PR+),(ER-)(PR-),(ER+)(PR-) endometrioid adenocarcinoma comparedwith the nomor endometrium,respectively,in each group the up-regulated genes and down-regulated gens were 902,751,907,849,1029and 1186.According to the Gene Ontology(Go) classified the gene into 16 kinds:binding,apoptosis,metabolism,cell cycle,signal transduction,transcription activation,etc.(2) There were specially differential expression genes 471 in the(ER+)(PR+) endometrioid adenocarcinoma,which up-regulated genes 399 and down-regulated genes 172.The special differential expression genes 645 in(ER-)(PR-) endometrioid adenocarcinoma,the up-regulated genes were 443,the down-regulated were 202.The special differential expression genes 1125 in(ER+)(PR-) endometrioid adenocarcinoma,the up-regulated genes were 608,the down-regulated were 567.(3)The difference expression genes 1177 were relatived with the estrogen receptor in which up-regulated genes 493 and down-regulated genes 684.According to the Gene Ontology(Go) classified the up-regulated genes into 31 kinds:cell mitosis,embrynomic,cranial skeleton morphogensis,immune response regulation,glycometabolism,DNA duplicate,and so on.The down-regulation genes kinds 27:T cell proliferation,angiopioesis,cell migration,cell adhesion,wound responds,signal transduction,etc.The difference expression genes 1413 were relatived with the progestrogen receptor in which up-regulated genes 814 and down-regulated genes 549. The up-regulated genes classified into 73 kinds:macrophage activied, defence virus,positive regulated the peptide,tyrosine phosporylation, amino acid metabolism,antigen presentation,etc.The down-regulated genes classified into 3 kinds:translation,biosynthesis,macromolecule biosynthetic prosess.There were difference expression genes 838 relatived to the expression of the ER and PR,in which up-regulated genes were 466 and down-regulated genes 372.The up-regulated genes classified into 65 kinds:negative regulation of lymphocyte activation,B cell proliferation,antigen processing and presentation of peptide antigen via MHC calss I,antigen processing and presentation of peptide antigen, etc.The down-regulated genes were classified kinds 4:gas transport, excretion,digestion,etc.(4) The differencial expression genes in the apoptosis pathway in endometrioid adenocarcinoma with(ER+)(PR+) were BIRC3,TNFSF10,NFκBIA,and in endomtrioid adenocarcinoma with(ER-)(PR-) were PDCD8,BIRC3,PRKACB,NFκBIA,PIK3R1, PIK3R3.but in endometrioid adenocarcinoma with(ER+)(PR-) were TP53,PDCD8,BIRC3,CASP7,NFκBIA,CHUK,PIK3CD,PIK3R1, PIK3R3,IL3RA,IL1A.(5) Vertifercail the genes by RT-PCR.The expression of INHBA were 26.37±15.35 in the normal endometrium, and were 117.68±44.15,45.96±29.02,37.14±31.03 in the (ER+)(PR+),(ER-)(PR-),(ER+)(PR-) endometrioid adenocarcinoma, respectively,When compared the endometrioid adenocarcinoma with the normal endometrium,there were significant defference between the endometrioid adenocarcinoma with(ER+)(PR+) and the normal(p＜0.05). There were no difference in the others(p＞0.05).The expression of FYN in normal were 83.24±32.30,but in endometrioid adenocarcinoma with (ER+)(PR+);(ER-)(PR-),(ER+)(PR-) were 48.01±38.29,18.01±19.67, 20.46±16.51,respectively.Compared each other,exceptes had no difference between(ER+)(PR+) endometrioid adenocarcinoma with the normal(p＞0.05),There were significant differernce in the others (p＜0.05).The expression of Cyr61 were 102.63±34.83 in normal endometrium and in the endometrioid adenocarcinoma with (ER+)(PR+),(ER-)(PR-),(ER+)(PR-) were 25.28±28.99,55.35±44.82, 10.23±11.06,respectively.Compared with each others,excepted no significant difference between the(ER-)(PR-) endometrioid adenocarcinoma with the normal endometrium(p＞0.05),there were significant difference in the others(p＜0.05).(6) The expression of Cyr61 were located in cell membrane and cytoplasm by immunohistochemistry. The positive appearance were color changed frome yellow to brown.The expression of Cyr61 in normal endometrium were 5.10±2.64 and in endometrioid adenocarcinoma with FIGO stageⅠ,stageⅡ,stageⅢwere 3.38±1.69,3.25±1.96,1.60±1.35,respectively.There were no difference when between the stageⅠand stageⅡ(p＞0.05),but there were significants difference not only in the stageⅠwith normal but also in the stageⅡwith normal endometrium(p＜0.05).The expression of Cyr61 in the endometioid adenocarcinoma with grade 1,grade 2 and grade 3 were 3.55±1.53,3.30±1.71,1.82±1.17.There no significant difference between the G1 and G2(p＞0.05),but there were significant defference not only between G1 and G3 but also between G2 and G3(p＜0.05).Conclusions:(1)There are many genes participated the etiopathogenisis of endometrioid adenocarcinoma(2) The various genes and the distinct apoptosis pathway along with the dictinct expression of the ER and PR played a crital roles in the prognosis of the endometrioid adenocarcinoma.(3) The ER or PR could regulate the variants gene expression.The ER up-regulated mitosis and negatived the T cell proliferation at the same time in favour the genesis of the endometrioid adenocarcinoma,the PR by up-regulated actived macrophage and down-regulated the transcription of ribosomal protein and the up-regulated negative regulate lympholyte and down-regulate the gas transport by ER and PR all participate the pathogenesis of the endometrioid adenocarcinoma.(4) The Cyr61 maybe regard as a target of the therapy in endometrioid adenocarcinoma.