mTOR、PI3K和P70S6K在子宫颈鳞癌中的表达及临床意义
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摘要
目的探讨mTOR、PI3K和P70S6K在子宫颈鳞癌发生、发展中的作用。方法用免疫组化SP法分别检测子宫颈鳞癌(宫颈癌组,55例)与正常宫颈组织(对照组,30例)中mTOR、PI3K和P70S6K的表达,分析其与各临床因素之间的关系。结果宫颈癌组mTOR、PI3K和P70S6K的阳性表达率均高于对照组(72.73%vs.10.00%、65.55%vs.0和52.73%vs.0)(P<0.01)。宫颈癌组mTOR阳性表达与间质浸润深度和淋巴结转移相关(P<0.05),PI3K阳性表达与肿瘤组织学分级相关(P<0.01),P70S6K阳性表达与肿瘤淋巴结转移相关(P<0.05)。宫颈癌组中mTOR与PI3K的表达呈正相关(r=0.50,P<0.01),mTOR与P70S6K的阳性表达呈正相关(r=0.32,P<0.05)。结论子宫颈鳞癌组织mTOR、PI3K和P70S6K蛋白表达与其发生、发展相关。
Objective TO investigate the expressions and clinical significance of mammalian target of rapamycin(mTOR),phosphatidylinositol 3-kinase(PI3 K) and 40 s small subunit ribosomal protein S6 kinase(P70 S6 K) in the occurrence and progression of cervical squamous cell carcinoma(SCC).Methods The expressions of mTOR,PI3 K and P70 S6 K were detected by SP immunohistochemistry in SCC(group SCC,55 cases)and normal cervical tissues(group NCE,30 cases).The correlation between the expressions of mTOR,PI3 K and P70 S6 K and clinicopathological features of cervical carcinoma was analyzed.Results The positive expression rates of mTOR,PI3 K and P70 S6 K were significantly higher in group SCC than those in group NCE(72.73% vs.10.00%,65.55% vs.0 and 52.73% vs.0)(P<0.01).The positive expression of mTOR in group SCC was closely correlated with the depth of tumor invasion and lymph node metastasis(P<0.05),which of PI3 K was correlated with the differentiation of tumor(r=0.50,P<0.01),and of P70 S6 K was correlated with the lymph node metastasis of tumor(r=0.32,P<0.05).Conclusion The expressions of mTOR,PI3 K and P70 S6 K in SCC tissues are involved in the occurrence and development of cervical carcinoma.
Objective TO investigate the expressions and clinical significance of mammalian target of rapamycin(mTOR),phosphatidylinositol 3-kinase(PI3 K) and 40 s small subunit ribosomal protein S6 kinase(P70 S6 K) in the occurrence and progression of cervical squamous cell carcinoma(SCC).Methods The expressions of mTOR,PI3 K and P70 S6 K were detected by SP immunohistochemistry in SCC(group SCC,55 cases)and normal cervical tissues(group NCE,30 cases).The correlation between the expressions of mTOR,PI3 K and P70 S6 K and clinicopathological features of cervical carcinoma was analyzed.Results The positive expression rates of mTOR,PI3 K and P70 S6 K were significantly higher in group SCC than those in group NCE(72.73% vs.10.00%,65.55% vs.0 and 52.73% vs.0)(P<0.01).The positive expression of mTOR in group SCC was closely correlated with the depth of tumor invasion and lymph node metastasis(P<0.05),which of PI3 K was correlated with the differentiation of tumor(r=0.50,P<0.01),and of P70 S6 K was correlated with the lymph node metastasis of tumor(r=0.32,P<0.05).Conclusion The expressions of mTOR,PI3 K and P70 S6 K in SCC tissues are involved in the occurrence and development of cervical carcinoma.
引文
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[2] Welker ME,Kulik G.Recent syntheses of PI3K/Akt/mTOR signaling pathway inhibitors[J].Bioorg Med Chem,2013,21(14):4063-4091.
[3] Hou LL,Gao C,Chen L,et al.Essential role of autophagy in fucoxanthin-induced cytotoxicity to human epithelial cervical cancer HeLa cells[J].Acta Pharmacol Sin,2013,34(11):1403-1410.
[4] Roy B,Pattanaik AK,Das J,et al.Role of PI3K/Akt/mTOR and MEK/ERK pathway in Concanavalin A induced autophagy in HeLa cells[J].Chem Biol Interact,2014 ,210:96-102.
[5] Faried LS,Faried A,Kanuma T,et al.Predictive and prognostic role of activated mammalian target of rapamycin in cervical cancer treated with cisplatin-based neoadjuvant chemotherapy[J].Oncol Rep,2006,16(1):57-63.
[6] Tanaka H,Yoshida M,Tanimura H,et al.The selective class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutations[J].Clin Cancer Res,2011,17(10):3272-3281.
[7] 谢丽云,陈雪初,刘琼.PI3K p110α在宫颈病变中的表达研究[J].实用预防医学,2011,18(3):417-419.
[8] 石海燕,左艳丽,林齐睿,等.子宫颈病变组织中HPV16感染与TLR4介导的PI3K/Akt信号通路相关蛋白表达的关系[J].临床与实验病理学杂志,2014,(11):1232-1236.
[9] Li X,Wu C,Chen N,et al.PI3K/Akt/mTOR signaling pathway and targeted therapy for glioblastoma[J].Oncotarget,2016,7(22):33440-33450.
[10] Monk BJ,Mas Lopez L,Zarba JJ,et al.Phase Ⅱ,open-label study of pazopanib or lapatinib monotherapy compared with pazopanib plus lapatinib combination therapy in patients with advanced and recurrent cervical cancer[J].J Clin Oncol,2010,28(22):3562-3569.
[11] Hiramatsu M,Ninomiya H,Inamura K,et al.Activation status of receptor tyrosine kinase downstream pathways in primary lung adenocarcinoma with reference of KRAS and EGFR mutations[J].Lung Cancer,2010,70(1):94-102.
[12] B?rlund M,Forozan F,Kononen J,et al.Detecting activation of ribosomal protein S6 kinase by complementary DNA and tissue microarray analysis[J].J Natl Cancer Inst,2000,92(15):1252-1259.
[13] Ji J,Zheng PS.Activation of mTOR signaling pathway contributes to survival of cervical cancer cells[J].Gynecol Oncol,2010,117(1):103-108.
[14] Bertram J,Peacock JW,Tan C,et al.Inhibition of the phosphatidylinositol 3′-kinase pathway promotes autocrine Fas-induced death of phosphatase and tensin homologue-deficient prostate cancer cells[J].Cancer Res,2006,66(9):4781-4788.