Chatrabnous, Nazanin

Simorgh Research Repository

utftr,rt",t,,.rS,.},,x oK-Lrl.l",(,i;4 ,r-l-U..i^ll q.i,it ,r-&el ,r-l'..l.JtS et!- *l:att!:,llJi.tSrl 3 oE -,3;, ottJ.,*, {., ){l. ,lrL.* ;.l IL-33 J IL-35 Lt'.y,ll';i. r#J}IL-33 r FO)G3 csl^.ri 1+r-rA l* cg-rt-#.7 - ..i. r -U-J+t;r?, Jj.Uu:x...3lro.ll;;i'r;, ,Srt.+. ;,iS.l :kat; l1j-,1cgtJlS .rt+" ;iS.l:;3[,i* .lti-l\f1A - tY12 :,rl*---: Jt-,ffi!-,JKerman University of Medical SciencesFaculty of MedicineIn Partial Fulfilknent of the Requirements for the DegreeMaster of ScienceTitle:Evaluation of the serum levels of IL-35 and IL-33 in patient with prostatecancer and the association of disease with FO)P3 and IL-33 genepolymorphismsBy:Nazanin ChatrabnousSupervisor:Dr. Abdollah JafarzadehAdvisor:Dr. Abbas GhaderiYear: 2017:0a552, l1 .r^q, ",l;.ii; .i--l Fi*yi, .cdl ..,1:f .-X.lJ 6,.U .SLooltf al-: ;1 ofl; ;ttr- :ei.r.5 9 c"JLot;;S .,9! y" dr.6*L .5.- (Treg) ,r^|tj T .St J*" 1l o.:',; ,j;;" IL-35 .r5.," A)L. e yi.it^J+ a..-a:>T.; q.r+ d/tt*L Jy IL-33 d;.7^b I S.,kr l;,Ssf i r,o .r"q.l.rt &!. slyC aJ c-|.**-1,"-.,=-.i"r-o .;11: )f i 4e,r---l .51o4-U 1: ,r^4." dladiil al c-l Syi r; [- f 6yy.;1i .5l.o:f.Lc L "-e FOXP3 6i ,:rs3761548 otf-t' SNP ;*Jdx+ eIL-33 9IL-35 ,-,"f" &" 6*1,)s1,AJU" ---.r9, (PCa)ob:,,+ uVr, { y:t"..r\,,L.:.,r IL-33 g) ;rs1929992 ,\*';- J-frU" ! o1;,r,r. ,Lr, ! y:, )1.^- \A' ;1 ,.5-r-oL;-:1y altt" ;l ,r :tao;9J I rl,oCt- .r; *sf of 6up ?f 1..! l/1\) *; &(;1* li JrJ 'tf ,:1yt q ,"JL .:r" \A. t (?dl.Y!Y ,'-.5l,oSNP , ELISA .5;t.; Lt df "1,5 I r6sy" + yitt" ,rlrt * rr"" 1r IL-33 ,IL-35 .gto.1,lS;qL -+.-.s$ ..r"r, PCR- RFLP .("it L )J-"9rS ,1 6)>r* 1$ a,.a\;-9l^ oLr" a, ){:*...,1,,[.*,,: IL-33 tIL-35 Ls")* et-,ir<t":taa;!!lL-33 9IL-35 ,r,/, et- .1r<t* ,cjrk* #lf d"Ll , .(P< 0.000i, P< 0.0001 .7*;i {) ry,j\'- - -q y:." ..r1,,[.,] ,,r .(P< 0.0001, P< 0.0001 e+'i +) cib .511:.p* ogli' ;,Vr" IV g III ,II ,I ].* --jl iY! .5;t.:,r;* 19t a, FOXP3 J i rs3761548 otK,-l-' ,r A .-pi , AA t -U'r;; ;lrlr-i ,oh-9,y, -- -,:rs1929992 .L<-t+ 1: G Ji e GG 1--b;j ;leli ;* 7"a .(P< 0.001, P< 0.003 i-*in {) )e4 e- :, -,t\*.tJL.r,59)P,r).(P<0.014,P<0.05t^*,r+) ,r'"JL "9f )i\\,3)rL;*,r:t+1L-:. -&. )\/YL .51b.-;-" ,eL a,rs3761548 otf.E ,: A ,pi 9 AA *-liij L rlr-il 1: IL-35 Ls"/, aL- -:- *.,l*ll,.JL,lffP,,:.F:up).(P<0.0001):9,C;pi9CC.-.b.,;1Urlil2rcr-l5r-L*- )l jVL .51b1- sS a" rs7929992 ,13'-lo- p G .-pi , GG *-br;; L :lr-il 1.: IL-33 Ls"r. 7L- -= . *Ji , GG ?-t ij , FOXP3 ;1 ; rs3761548 ot(L A ,-li t AA ,-."-L'ei; or"i c--r, e-r; -*-at- ;*+-o .ru;.ib ot;e x rsL.y { y+..,1,,1q:.1r \ GUp ar.,& IL-33 aj prst929992 otf._};l ,e"Ll ixl .r .rl rs1929992 9rs376l548.St .li-l+ SNP ,.iti c-ni e-ii a, IL-33 9E--35..:u,iL a;ilr &hrx c.rL.p .s,rtqt $/i#" 9 ),bltLi;-lp ct'{d,;;ij c-l 65-"rs1929992 ,rs3761548 ,;j y44,.A,fY-OJ/,:+.lfa-;,Jl"al,ot:-9;, .rU,,-:bo;19 qlf.'-J$l o{ibAbstract:Background and Aims: Prostate cancer (PCa) is one of the most common cancer in the men.The immune system plays an important role against tumor cells. The regulatory T (Treg) cell-derived IL-35 is an immunosuppressive cytokine that may inhibits antitumor immune responsesand also IL-33 anovel identified cytokine with both pro- or anti-tumor activities, play importantroles in response against tumor cells. The aim of this study was to evaluate the serum levels ofIL-35 and IL-33 and single nucleotide polymoqphisms (SNP) in FOXP3 and IL-33 genes inpatients with PCa.Material and Methods: In this case/control study, the blood samples collected from 150 PCapatients (mean age 65.07 + 7.88, year) and 150 healthy men (mean age 64.00 t 8.91, years) asa controi group.The serum levels of IL-35 and IL-33 and the mentioned SNPs were determinedby ELISA and PCR-restriction fragment length polymorphism (PCR-RFLP) methods,respectivelyResults: The mean serum IL-35 and IL-33 levels in patients with PCa were significantly higherin comparison to healthy control group (P<0.0001 and P<0.0001, respectively). There weresignificant differences between patients with Stages I, II, III and IV regarding the serum levelsof IL-33 and IL-35 (P<0.0001 and P<0.0001, respectively). In patients with prostate cancer, thefrequencies of AA genotype and A allele at rs3761548 were significantly higher than in healthycontrols (P <0.003, P <0.0001, respectively). Moreover, the frequencies of GG genotype and Gallele at rs1929992 were significantly higher than in healthy controls (P <0.003, P <0.014,respectively). In both patients and control groups, the mean serum levels of IL-35 in subjectswith AA genotype or A allele at rs3761548 were also significantly higher as compared tosubjects with CC genotype or C allele (P <0.0001). On the other hand, in both patients andcontrol groups, the mean semm levels of IL-33 in subjects with GG genotype or G allele atrs1929992 were also significantly higher as compared to subjects with AA genotype or A allele(P <0.0001).Conclusion: These findings represent that the IL-35 and lL-33 may contribute in tumordevelopment. The AA genotype and A allele at rs3761548 were more frequent in PCa patients.Whereas, the GG genotype and G allele at rs1929992 were more frequent. The serum IL-35md IL-33 levels were respectively affected by genetic variations at SNP rs3761548 and SNPs1929992. Accordingly, these SNP may play arole in the susceptibility to PCa.I(eywords: Prostate cancer, Interleukin-35, Interleukin-33, Polymorphism, rs3761548,w,1929992

بررسی میزان سرمیIL-35 و IL-33 در بیماران مبتلا به سرطان پروستات و ارتباط بیماری با پلی مورفیسم ژن های FOXP3 و IL-33

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