Skp1蛋白在非小细胞肺癌组织和外周血中的表达水平及其临床意义

doi:10.3969/j.issn.1004-616x.2019.02.001

Abstract

Abstract: OBJECTIVE:To detect the protein expression of Skp1(S-phase kinase-associated protein 1) in non-small cancer lung cancer (NSCLC) tissues and peripheral blood,and to explore its clinical significance.METHODS:Expressions of Skp1 protein in 34 NSCLC tissues and 34 adjacent tissues were detected by Western Blot.In addition,the expressions in 86 NSCLC tissues and 86 adjacent tissues were detected by tissue microarray and immunohistochemical staining method.The plasma expression level of Skp1 in 39 NSCLC patients and 27 healthy person was detected by ELISA (enzyme linked immunesorbent assay).The relationships between Skp1 expression with clinicopathological parameters and prognosis of NSCLC patients were analyzed.RESULTS:The expression level of Skp1 protein in NSCLC tissues was significantly higher than that in adjacent tissues by both Western blot and immunohistochemical staining methods (P < 0.01).The plasma levels in NSCLC patients were significantly higher than that in healthy person (P=0.003).The simple factors analyses show that over-expression of Skp1 protein in NSCLC tissues was significantly associated with poor prognosis in the middle to late cancer stages (Ⅱ+Ⅲ)(P=0.001),and the multiple factors Cox regression analysis showed that Skp1 protein could be used as the independent risk factors for the middle to late stages (Ⅱ+Ⅲ).The expression of Skp1 protein had no correlation with pathological type,clinical stage,pathological grade,lymph node metastasis and other factors (P > 0.05).CONCLUSION:Skp1 protein was over-expressed in NSCLC tissues and plasma from patients,and the over-expression of Skp1 protein in NSCLC tissues was significantly associated with poor prognosis in the middle to late cancer stages (Ⅱ+Ⅲ).Therefore,the over-expression can be considered for use as an independent risk factor for the middle to late stages among NSCLC patients.

Key words: Skp1, non-small cell lung cancer, prognosis, risk factors

CLC Number:

R730.7

ZHU Jiawei, HU Xiao, WANG Xijun, WANG Yaru, FENG Lin, XIAO Ting. Clinical significance of Skp1 protein expression in non-small cell lung cancer tissues and peripheral blood[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2019, 31(2): 89-95.

References

[1] BLANDIN KNIGHT S,CROSBIE P A,BALATA H,et al. Progress and prospects of early detection in lung cancer[J]. Open Biol,2017,7(9):170070.
[2] TARTARI R F,ULBRICH-KULCZYNSKI J M,FILHO A F. Measurement of mid-arm muscle circumference and prognosis in stage IV non-small cell lung cancer patients[J]. Oncol Lett,2013,5(3):1063-1067.
[3] HUSSAIN M,LU Y,LIU Y Q,et al. Skp1:Implications in cancer and SCF-oriented anti-cancer drug discovery[J]. Pharmacol Res,2016,111:34-42.
[4] KUHN D J,CHEN Q,VOORHEES P M,et al. Potent activity of carfilzomib,a novel,irreversible inhibitor of the ubiquitin-proteasome pathway,against preclinical models of multiple myeloma[J]. Blood,2007,110(9):3281-3290.
[5] RICHARDSON P G,SONNEVELD P,SCHUSTER M W,et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma[J]. N Engl J Med,2005,352(24):2487-2498.
[6] HERSHKO A,CIECHANOVER A. The ubiquitin system[J]. Annu Rev Biochem,1998,67:425-479.
[7] YOSHIDA Y,MURAKAMI A,TANAKA K. Skp1 stabilizes the conformation of F-box proteins[J]. Biochem Biophys Res Commun,2011,410(1):24-28.
[8] SKAAR J R,PAGAN J K,PAGANO M. Mechanisms and function of substrate recruitment by F-box proteins[J]. Nat Rev Mol Cell Biol,2013,14(6):369-381.
[9] GSTAIGER M,MARTI A,KREK W. Association of human SCF(SKP2) subunit p19(SKP1) with interphase centrosomes and mitotic spindle poles[J]. Exp Cell Res,1999,247(2):554-562.
[10] CHANDRA DANTU S,NATHUBHAI KACHARIYA N,KUMAR A. Molecular dynamics simulations elucidate the mode of protein recognition by Skp1 and the F-box domain in the SCF complex[J]. Proteins,2016,84(1):159-171.
[11] BAI C,SEN P,HOFMANN K,et al. Skp1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif,the F-box[J]. Cell,1996,86(2):263-274.
[12] LIU Y Q,WANG X L,CHENG X,et al. Skp1 in lung cancer:clinical significance and therapeutic efficacy of its small molecule inhibitors[J]. Oncotarget,2015,6(33):34953-34967.
[13] WANG Z,LIU P,INUZUKA H,et al. Roles of F-box proteins in cancer[J]. Nat Rev Cancer,2014,14(4):233-247.
[14] REMMELE W,STEGNER H E. Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue[J]. Pathologe,1987,8(3):138-140.
[15] WANG X,ZHANG S,ZHANG T,et al. Prognostic values of F-box members in breast cancer:an online database analysis and literature review[J]. Biosci Rep,2018. pii:BSR20180949.
[16] YU Z K,GERVAIS J L,ZHANG H. Human CUL-1 associates with the SKP1/SKP2 complex and regulates p21(CIP1/WAF1) and cyclin D proteins[J]. Proc Natl Acad Sci USA,1998,95(19):11324-11329.
[17] XU M,YANG X,ZHAO J,et al. High expression of Cullin1 indicates poor prognosis for NSCLC patients[J]. Pathol Res Pract,2014,210(7):397-401.
[18] HUANG Y F,ZHANG Z,ZHANG M,et al. CUL1 promotes breast cancer metastasis through regulating EZH2-induced the autocrine expression of the cytokines CXCL8 and IL11[J]. Cell Death Dis,2018,10(1):2.
[19] KIMBREL E A,KUNG A L. The F-box protein beta-TrCp1/Fbw1a interacts with p300 to enhance beta-catenin transcriptional activity[J]. J Biol Chem,2009,284(19):13033-13044.
[20] WANG J Y,LIU G Z,WILMOTT J S,et al. Skp2-mediated stabilization of MTH1 promotes survival of melanoma cells upon oxidative stress[J]. Cancer Res,2017,77(22):6226-6239.
[21] TAKANAMI I. The prognostic value of overexpression of Skp2 mRNA in non-small cell lung cancer[J]. Oncol Rep,2005,13(4):727-731.
[22] ZHANG Y,ZVI Y S,BATKO B,et al. Down-regulation of Skp2 expression inhibits invasion and lung metastasis in osteosarcoma[J]. Sci Rep 2018,8(1):14294.
[23] DING L,LI R,SUN R,et al. S-phase kinase-associated protein 2 promotes cell growth and motility in osteosarcoma cells[J]. Cell Cycle,2017,16(16):1547-1555.
[24] DING L,LI R,HAN X,et al. Inhibition of Skp2 suppresses the proliferation and invasion of osteosarcoma cells[J]. Oncol Rep,2017,38(2):933-940.
[25] LIU W,WANG Y,ZHANG C,et al. Cullin1 is up-regulated and associated with poor patients' survival in hepatocellular carcinoma[J]. Int J Clin Exp Pathol,2015,8(4):4001-4007.
[26] MIGITA K,TAKAYAMA T,MATSUMOTO S,et al. Prognostic impact of RING box protein-1(RBX1) expression in gastric cancer[J]. Gastric Cancer,2014,17(4):601-609.
[27] RUAN D,HE J,LI C F,et al. Skp2 deficiency restricts the progression and stem cell features of castration-resistant prostate cancer by destabilizing Twist[J]. Oncogene,2017,36(30):4299-4310.

Clinical significance of Skp1 protein expression in non-small cell lung cancer tissues and peripheral blood

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	PENG Youbin, LIN Hao, LI Ming, HUANG Haihua. Expression of TPX2 and its clinicalsignificance in non-muscle-invasive bladder cancer [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2022, 34(1): 30-34.
[2]	JIAO Wenpeng, HOU Lin, CUI Meijuan, JIAO Wenjing, MA Ming, ZHANG Jinyan. Expression of miR-93-5p and miR-106b-5p in alcohol-related liver cancer and its clinical significance [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(6): 430-434.
[3]	GAO Xiaobin, WU Xueliang, WANG Shengjie, SUN Guangyuan, WANG Wenjing, LIANG Feng, ZHAO Yifeng, LIU Zhenxian, ZHANG Yingchun. Expression of TRIM59 and its correlations with clinicopathological features in colorectal cancers [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(6): 446-450.
[4]	JIAO Wenjing, ZHANG Jinyan, MA Ming, GUO Xiujuan, FENG Junhua, SHAO Junguo, JIAO Wenpeng. Expression and clinical significance of MTDH and FoxM1 in hepatocellular carcinomas [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(5): 349-353,359.
[5]	ZHANG Shimin, ZHAO Ruijun. Expression of protein tyrosine phosphatase receptor J in breast cancer tissues and its relationship with clinical prognosis [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(4): 276-279,285.
[6]	LIU Xiaoxia, LI Weixia, LI Zhijia, SU Zhenjun, DUAN Xiaohui, HAN Weiwen, WANG Yunxiao, HE Xiaolei, Lu Linlin, JIA Jinhai. Correlations between glutathione peroxidase in serum and clinicopathological outcomes of advanced non-small cell lung cancer [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(4): 286-290,295.
[7]	WANG Xikai, MENG Qinghe, GAO Yanlu. miR-223-3p negatively regulated ECT2 to induce apoptosis in non-small cell lung cancer cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(3): 187-192.
[8]	ZHANG Yuling, WU Jundong, PANG Dongyue, CHEN Chunfa. Changes of Ki67 expression before and after neoadjuvant chemotherapy as a predictor for therapeutic response and rognosis in breast cancers [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(3): 230-235,245.
[9]	SHI Hailin, HE Tianji, LIU Feng, CAI Menghui, GE Bo. Prognostic value of TCGA-database mutation burden in muscle-invasive bladder cancers [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(6): 430-437,443.
[10]	DING Yawen, JIAO Wenjing, WANG Pengyu, LU Gang, MA Ming. Immunophenotype characteristics of plasma cells and clinical significance in multiple myeloma patients [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(6): 464-468,489.
[11]	LIU Xiaoxia, LI Weixia, SU Zhenjun, JIA Jinhai, DUAN Xiaohui, LI Zhijia, HE Xiaolei, L Linlin, LIU Rui, WANG Yunxiao. Analyses of clinicopathological characteristics and curative effect of combined radio-with chemo-therapy for advanced non-small cell lung cancer with superoxide dismutase activity in serum [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(5): 350-354.
[12]	SHAO Junguo, JIAO Wenjing, WANG Xuexiao, ZHANG Jinyan, MA Ming. Clinical significance of mi-429 and Bmi-1 mRNA expressions in lung carcinoma tissues [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(5): 369-373.
[13]	Lü Yanping, WU Chuancheng, YANG Shuangfeng, HE Chenzhou, HAN Renjie, YAN Wei, LIU Baoying. Relationship between differentially expressed miRNA-SNPs and prognosis of gastric cancer [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(5): 380-386.
[14]	GUO Xiujuan, DU Yanyan, YAN Xi, ZHAO Xuetao, HAN Lina, WU Yipeng, WANG Xuexiao, MA Ming. Expression and clinical significance of CREB in esophageal squamous cell carcinoma tissues [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(5): 387-390,394.
[15]	YANG Li, ZHANG Mengxian, ZHANG Wei, XIONG Yingyou, CHEN Shiyong, FANG Chengxiang. Data mining to investigate expression and significance of aurora kinase A in esophageal carcinoma [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(3): 221-228.