组织蛋白酶D新的糖基化异构体在肺癌中表达的临床意义及其与预后的相关性

doi:10.16098/j.issn.0529-1356.2018.02.009

解剖学报 ›› 2018, Vol. 49 ›› Issue (2): 191-197.doi: 10.16098/j.issn.0529-1356.2018.02.009

组织蛋白酶D新的糖基化异构体在肺癌中表达的临床意义及其与预后的相关性

张慧娟¹ 郑晓伟^1,2乔玲¹ 李鸿超³常文静¹卢锋^1* 贾彩云^1*

1.河南大学抗体药物开发技术国家地方联合工程实验室，河南开封 475004; 2.河南省濮阳市中医院检验科，河南濮阳 475000; 3.河南省濮阳市油田总医院病理科，河南濮阳 475000

收稿日期:2017-05-26 修回日期:2017-11-29 出版日期:2017-04-06 发布日期:2018-04-06
通讯作者: 卢锋;贾彩云 E-mail:jcy2668@163.com
基金资助:
Cathepsin D新的糖基化异构体在肺癌发生发展中的作用及分子机制

Clinical significance and correlation with prognosis of novel glycosylation isoform of cathepsin D expression in lung cancer

ZHANG Hui-juan¹ ZHENG Xiao-wei ^1,2 QIAO Ling¹LI Hong-chao³ CHANG Wen-jing¹ LU Feng ^1* JIA Cai-yun ^1*

1.He’nan University Joint National Laboratory for Antibody Drug Engineering,He’nan Kaifeng 475004, China; 2.Department of Clinical Laboratory，Puyang Hospital of Traditional Chinese Medicine, He’nan Puyang 475000, China; 3.Department of Pathology, Puyang Oilfeld General Hospital, He’nan Puyang 475000, China

Received:2017-05-26 Revised:2017-11-29 Online:2017-04-06 Published:2018-04-06
Contact: LU Feng; JIA Cai-yun E-mail:jcy2668@163.com

摘要/Abstract

摘要：

目的探讨组织蛋白酶D（CTSD）新的糖基化异构体与肺癌临床病理特征及预后的相关性。方法应用免疫组织化学和半定量RTPCR方法检测119例肺癌组织和39例癌旁组织中CTSD的表达；Western blotting分析CTSD各异构体表达特点；去糖基化实验检测CTSD 蛋白的糖基化修饰；Kaplan-Meier分析66kD异构体、临床病理资料与肺癌术后整体生存期的相关性。结果 CTSD在肺鳞癌、腺癌和小细胞肺癌组织中高表达；66kD蛋白为CTSD新的糖基化异构体，该异构体表达与肺癌组织类型、临床分期、淋巴结转移和患者的吸烟史密切相关（P<0.05），阳性表达和阴性表达患者术后中位生存时间分别为20.0和30.0个月（P<0.05）；肺癌组织类型、临床分期、淋巴结转移、肿瘤大小和66kD异构体表达是影响肺癌预后的独立因素。结论 CTSD 66kD异构体阳性表达可能是肺癌预后不良的分子标志物之一。

关键词: 肺癌, 组织蛋白酶D, 糖基化异构体, 免疫印迹法, 人

Abstract:

Objective To study the correlation of novel glycosylation isoform of cathepsin D (CTSD) expression with clinical features and its prognostic value in lung cancer.Methods Immunohistochemistry and Semi-quantitative RT-PCR were used to examine the cathepsin D expression, and Western blotting to analyze characterization of cathepsin D isoforms expression in 119 lung cancer tissues and 39 paraneoplastic tissues. Deglycosylation experiment was performed to check glycosylation-modified condition of cathepsin D. The association of 66kD isoform expression with clinical features and lung cancer prognosis was determined by Kaplan-Meier survival analysis. Results Cathepsin D highly expressed in squamous carcinomas, adenocarcinoma and small cell carcinoma tissues. 66kD protein form of cathepsin D was a novel glycosylation isoform of cathepsin D, its expression was associated with lung cancer histological type, clinical stage, lymph node metastasis and smoking status(P<0.05). The median survival time of lung cancer with 66kD isoform positive and negative expression were 20.0 months and 30.0 months, respectively (P<0.05). Histological type, clinical stage, lymph node metastasis, tumor size and 66kD isoform were independent prognostic factor of lung cancer. Conclusion Positive expression of 66kD isoform of cathepsin D may be one of molecular markers which correlate with poor prognosis of lung cancer.

Key words: Lung cancer, Cathepsin D, Glycosylation isoform, Western blotting, Human

张慧娟郑晓伟乔玲李鸿超常文静卢锋贾彩云. 组织蛋白酶D新的糖基化异构体在肺癌中表达的临床意义及其与预后的相关性[J]. 解剖学报, 2018, 49(2): 191-197.

ZHANG Hui-juan ZHENG Xiao-wei QIAO Ling LI Hong-chao CHANG Wen-jing LU Feng JIA Cai-yun. Clinical significance and correlation with prognosis of novel glycosylation isoform of cathepsin D expression in lung cancer[J]. Acta Anatomica Sinica, 2018, 49(2): 191-197.

参考文献

［1］ Satelur KP, Kumar GS. Immunohistochemical expression of Cathepsin D in primary and recurrent sequanmous cell carcinoma［J］. J Contemp Dent Pract, 2017, 18(9): 795-801.

［2］Downs LS, Lima PH, Bliss RL, et al. Cathepsins B and D activity and activity ratios in normal ovaries, benign ovarian neoplasms, and epithelial ovarian cancer［J］. J Soc Gynecol Investig, 2005, 12(7): 539-544.

［3］Berchem G, Glondu M, Gleizes M, et al. Cathepsis D affects multiple tumor progression steps in vivo: proliferation, angiogenesis and apoptosis［J］. Oncogene, 2002, 21(38):5951-5955.

［4］Mimae T, Tsuta K, Maeshima AM, et al. Cathepsin D as a potential prognostic marker for lung adenocarcinoma［J］. Pathol Res Pract, 2012,208(9): 534-540.

［5］Pranjol MZ, Gutowski N, Hannemann M, et al. The potential role of the proteases cathepsin D and cathepsin L in the progression and metastasis of epithelial ovarian cancer［J］. Biomolecules, 2015, 5(4): 3260-3279.

［6］Vashishta A, Ohri SS, Proctor M, et al. Role of activation peptide of procathepsin D in proliferation and invasion of lung cancer cells［J］. Anticancer Res, 2006, 26(6B): 4163-4170. ［7］Iacobuzio-Donahue C, Shuja S, Cai J, et al. Cathepsin D protein levels in colorectal tumors: Divergent expression patterns suggest complex regulation and function［J］. Int J Oncol, 2004， 24(3): 473-485.

［8］Gemoll T, Epping F, Heinrich L, et al. Increased cathepsin D protein expression is a biomarker for osteosarcomas, pulmonary metastases and other bone malignancies［J］. Oncotarget, 2015, 6(18): 16517-16526.

［9］Luo X, Lu F, Wang HL, et al. Comparative autoantibody profiling before and after the appearance of malignancy: identification of anti-cathepsin D autoantibody as a promising diagnostic marker for lung cancer ［J］. Biochem Biophys Res Commun, 2012, 420(4): 704-709.

［10］Cohen PA Mak KM , Rosman AS,et al.Immunohistochemicaal determination of hepatic cytochrome P-4502El in formalin-fixed,paraffin-embedded sections[J].Alcoho Clin Exp Res,1997,21(6):1057-1062.

[11] Pohlodek K, Galbavy S, Bartosova M, et al. Semi-quantitative RT-PCR assessment of molecular markers in breast large-coreneedle biopsies［J］. Neoplasma, 2004, 51(6):415-421.［12］Katayama K, Nakamura A, Sugimoto Y, et al. FOXO transcription factor-dependent p15(INK4b) and p19(INK4d) expression［J］. Ongcogene, 2008, 27(12): 1677-1686.

［13］Pruitt FL, He Y, Franco OE, et al. Cathepsin D acts as an essential mediator to promote malignancy of benign prostatic epithelium［J］. Prostate, 2012,10(1002):22589-22601.

［14］Pigac B, Dmitrovic B, Maric S, et al. Cathepsin D and its prognostic value in neuroepithelial brain tumors［J］. CollAntropol, 2012, 36(1):227-233.

［15］Arao J, Fukui H, Ono Y, et al. Immunohistochemical localization of cathepsin D in colorectal tumors［J］. Dis Colon Rectum, 2000, 43(3): 396-401.

［16］Hara I, Miyake H, Yamanaka K, et al. Serum cathepsin D and its density in men with prostate cancer as new predictors of disease progression［J］. Oncol Rep, 2002, 9(6): 1379-1383.

［17］Yang L, Cui M, Zhang L, et al. FOXM1 facilitates gastric cancer cell migration and invasion by inducing Cathepsin D［J］.Oncotarget, 2017, 8(40): 68180-68190.

［18］Varki A. Biological roles of oligosaccharides: all of the theories are correct［J］.Glycobiology, 1993, 3(2):97-130.

［19］Dwek RA. Glycobiology:‘towards understanding the function of sugars’ ［J］. Biochem Soc Trans, 1995,23(1):1-25.

［20］Zhao Y, Takahashi M, Gu J, et al. Functional roles of N-glycans in cell signaling and cell adhesion in cancer［J］. Cancer Sci, 2008, 99(7):1304-1310.

［21］Taniguchi N, Miyoshi E, Gu J, et al. Decoding sugar functions by identifying target glycoproteins［J］. Curr Opin Struct Biol, 2006, 16(6):561-566.

［22］Carpelan HM, Louhima J, Stenman UH, et al. Estimating the probability of cancer with several tumor markers in patients with colorectal disease［J］. Oncology, 2004, 66(4):296-302.

［23］Yi W, Clark PM, Mason DE, et al. Phosphofructokinase 1 glycosylation regulates cell growth and metabolism［J］. Science, 2012, 337(6097):975-980.

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组织蛋白酶D新的糖基化异构体在肺癌中表达的临床意义及其与预后的相关性

Clinical significance and correlation with prognosis of novel glycosylation isoform of cathepsin D expression in lung cancer

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