目的 探討磷酸化的哺乳動(dòng)物雷帕霉素靶蛋白(p-roTOR)在非小細(xì)胞肺癌(NSCLC) 中的表達(dá)及其對(duì)預(yù)后的預(yù)測(cè)價(jià)值。方法 運(yùn)用免疫組織化學(xué)EnVision法檢測(cè)59例NSCLC肺癌組織和10例非肺癌組織(3例肺結(jié)核和7例炎性假瘤)中p-mTOR蛋白的表達(dá)。結(jié)果 p-mTOR在肺 良性疾病組均為陰性,在NSCLC組織中表達(dá)的陽(yáng)性率為40.7%,顯著高于肺良性疾病組(χ2=6.237,P=0.013);p-mTOR在NSCLC組織中的表達(dá)與性別、年齡和pTNM分期有關(guān),而與其他臨床 病理參數(shù)(腫瘤大小、病理類(lèi)型和淋巴結(jié)轉(zhuǎn)移情況)無(wú)明顯相關(guān)性。Kaplan-Meire生存分析顯示, p-mTOR與生存期無(wú)明顯相關(guān)(Log rank檢驗(yàn)P=0.055)。結(jié)論 檢測(cè)p-mTOR有助于肺部良惡性疾病的鑒別,單獨(dú)p-mTOR不能作為判斷NSCLC預(yù)后的參考指標(biāo)。
引用本文: 劉紅兵,宋勇,吳穎. p-mTOR在Ⅰ~Ⅲ期非小細(xì)胞肺癌組織中的表達(dá)及其與預(yù)后的關(guān)系. 中國(guó)呼吸與危重監(jiān)護(hù)雜志, 2008, 08(5): 354-357. doi: 復(fù)制
1. | Sabatini DM,Erdjument-Bromage H,Lui M,et al.RAFT1:a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs.Cell,1994,78:35-43. |
2. | Brown EJ,Albers MW,Shin TB,et al.A mammalian protein targeted by G1-arresting rapamycin-receptor complex.Nature,1994,369:756-758. |
3. | Balsara BR,Pei J,Mitsuuchi Y,et al.Frequent activation of AKT in non-small cell lung carcinomas and preneoplastic bronchial lesions.Carcinogenesis,2004,25:2053-2059. |
4. | Herberger B,Puhalla H,Lehnert M,et al,Activated mammalian target of rapamycin is an adverse prognostic factor in patients with biliary tract adenocarcinoma.Clin Cancer Res,2007,13:4795-4799. |
5. | Gera JF,Mellinghoff IK,Shi Y,et al.AKT activity determines sensitivity to mammalian target of rapamycin(mTOR) inhibitors by regulating cyclin D1 and c-myc expression.J Biol Chem,2004,279:2737-2746. |
6. | Bjornsti MA,Houghton PJ.The TOR pathway:a target for cancer therapy.Nat Rev Cancer,2004,4:335-348. |
7. | Nave BT,Ouwens M,Withers DJ,et al.Mammalian target of rapamycin is a direct target for protein kinase B:identification of a convergence point for opposing effects of insulin and amino-acid deficiency on protein translation.Biochem J,1999,344:427-431. |
8. | Sekulic A,Hudson CC,Homme JL,et al.A direct linkage between the phosphoinositide 3-kinase-AKT signaling pathway and the mammalian target of rapamycin in mitogen-stimulated and transformed cells.Cancer Res,2000,60:3504-3513. |
9. | Scott PH,Lawrence JC Jr.Attenuation of mammalian target of rapamycin activity by increased cAMP in 3T3–L1 adipocytes.J Biol Chem,1998,273:34496-34501. |
10. | Reynolds TH 4th,Bodine SC,Lawrence JC Jr.Control of Ser2448 phosphorylation in the mammalian target of rapamycin by insulin and skeletal muscle load.J Biol Chem,2002,277:17657-17662. |
11. | Sahin F,Kannangai R,Adegbola O,et al.mTOR and P70 S6 Kinase Expression in Primary Liver Neoplasms.Clin Cancer Res,2004,10:8421-8425. |
12. | Zhou X,Tan M,Stone Hawthorne V,et al.Activation of the Akt/Mammalian Target of Rapamycin/4E-BP1 Pathway by ErbB2 Overexpression Predicts Tumor Progression in Breast Cancers.Clin Cancer Res,2004,10:6779-6788. |
13. | Faried LS,F(xiàn)aried A,Kanuma T,et al.Predictive and prognostic role of activated mammalian target of rapamycin in cervical cancer treated with cisplatin-based neoadjuvant chemotherapy.Oncol Rep,2006,16:57-63. |
14. | Kremer CL,Klein RR,Mendelson J,et al.Expression of mTOR Signaling PathwayMarkers in Prostate Cancer Progression.Prostate,2006,66:1203-1212. |
15. | Sieghart W,F(xiàn)uereder T,Schmid K,et al.Mammalian target of rapamycin pathway activity in hepatocellular carcinomas of patients undergoing liver transplantation.Transplantation,2007,83:425-432. |
16. | Atkins MB,Hidalgo M,Stadler WM,et al.Randomized phase II study of multiple dose levels of CCI-779,a novel mammalian target of rapamycin kinase inhibitor,in patients with advanced refractory renal cell carcinoma.J Clin Oncol,2004,22:909-918. |
17. | Witzig TE,Geyer SM,Ghobrial I,et al.Phase II trial of single-agent temsirolimus(CCI-779) for relapsed mantle cell lymphoma.J Clin Oncol,2005,23:5347-5356. |
18. | Galanis E,Buckner JC,Maurer MJ,et al.Phase II trial of temsirolimus(CCI-779) in recurrent glioblastoma multiforme:a North Central Cancer Treatment Group Study.J Clin On col,2005,23:5294-5304. |
19. | Chan S,Scheulen ME,Johnston S,et al.Phase II study of temsirolimus(CCI-779),a novel inhibitor of mTOR,in heavily pretreated patients with locally advanced or metastatic breast cancer.J Clin Oncol,2005,23:5314-5322. |
- 1. Sabatini DM,Erdjument-Bromage H,Lui M,et al.RAFT1:a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs.Cell,1994,78:35-43.
- 2. Brown EJ,Albers MW,Shin TB,et al.A mammalian protein targeted by G1-arresting rapamycin-receptor complex.Nature,1994,369:756-758.
- 3. Balsara BR,Pei J,Mitsuuchi Y,et al.Frequent activation of AKT in non-small cell lung carcinomas and preneoplastic bronchial lesions.Carcinogenesis,2004,25:2053-2059.
- 4. Herberger B,Puhalla H,Lehnert M,et al,Activated mammalian target of rapamycin is an adverse prognostic factor in patients with biliary tract adenocarcinoma.Clin Cancer Res,2007,13:4795-4799.
- 5. Gera JF,Mellinghoff IK,Shi Y,et al.AKT activity determines sensitivity to mammalian target of rapamycin(mTOR) inhibitors by regulating cyclin D1 and c-myc expression.J Biol Chem,2004,279:2737-2746.
- 6. Bjornsti MA,Houghton PJ.The TOR pathway:a target for cancer therapy.Nat Rev Cancer,2004,4:335-348.
- 7. Nave BT,Ouwens M,Withers DJ,et al.Mammalian target of rapamycin is a direct target for protein kinase B:identification of a convergence point for opposing effects of insulin and amino-acid deficiency on protein translation.Biochem J,1999,344:427-431.
- 8. Sekulic A,Hudson CC,Homme JL,et al.A direct linkage between the phosphoinositide 3-kinase-AKT signaling pathway and the mammalian target of rapamycin in mitogen-stimulated and transformed cells.Cancer Res,2000,60:3504-3513.
- 9. Scott PH,Lawrence JC Jr.Attenuation of mammalian target of rapamycin activity by increased cAMP in 3T3–L1 adipocytes.J Biol Chem,1998,273:34496-34501.
- 10. Reynolds TH 4th,Bodine SC,Lawrence JC Jr.Control of Ser2448 phosphorylation in the mammalian target of rapamycin by insulin and skeletal muscle load.J Biol Chem,2002,277:17657-17662.
- 11. Sahin F,Kannangai R,Adegbola O,et al.mTOR and P70 S6 Kinase Expression in Primary Liver Neoplasms.Clin Cancer Res,2004,10:8421-8425.
- 12. Zhou X,Tan M,Stone Hawthorne V,et al.Activation of the Akt/Mammalian Target of Rapamycin/4E-BP1 Pathway by ErbB2 Overexpression Predicts Tumor Progression in Breast Cancers.Clin Cancer Res,2004,10:6779-6788.
- 13. Faried LS,F(xiàn)aried A,Kanuma T,et al.Predictive and prognostic role of activated mammalian target of rapamycin in cervical cancer treated with cisplatin-based neoadjuvant chemotherapy.Oncol Rep,2006,16:57-63.
- 14. Kremer CL,Klein RR,Mendelson J,et al.Expression of mTOR Signaling PathwayMarkers in Prostate Cancer Progression.Prostate,2006,66:1203-1212.
- 15. Sieghart W,F(xiàn)uereder T,Schmid K,et al.Mammalian target of rapamycin pathway activity in hepatocellular carcinomas of patients undergoing liver transplantation.Transplantation,2007,83:425-432.
- 16. Atkins MB,Hidalgo M,Stadler WM,et al.Randomized phase II study of multiple dose levels of CCI-779,a novel mammalian target of rapamycin kinase inhibitor,in patients with advanced refractory renal cell carcinoma.J Clin Oncol,2004,22:909-918.
- 17. Witzig TE,Geyer SM,Ghobrial I,et al.Phase II trial of single-agent temsirolimus(CCI-779) for relapsed mantle cell lymphoma.J Clin Oncol,2005,23:5347-5356.
- 18. Galanis E,Buckner JC,Maurer MJ,et al.Phase II trial of temsirolimus(CCI-779) in recurrent glioblastoma multiforme:a North Central Cancer Treatment Group Study.J Clin On col,2005,23:5294-5304.
- 19. Chan S,Scheulen ME,Johnston S,et al.Phase II study of temsirolimus(CCI-779),a novel inhibitor of mTOR,in heavily pretreated patients with locally advanced or metastatic breast cancer.J Clin Oncol,2005,23:5314-5322.