阶段相关生物标志物PPIA、YWHAZ和GRP78是结直肠癌的潜在预后指标  

Stage-Associated Biomarkers PPIA,YWHAZ and GRP78 are Potential Prognostic Indicators of Colorectal Cancer

作　　者：彭娅[1] 贺艳玲 张军玲 陈智远[1] 成瑾瑜 杨瑜明[1] 沈守荣 孙英男 Ya peng;Yanling He;Junling Zhang;Zhiyuan Chen;Jinyu Cheng;Yuming Yang;Shourong Shen;Yingnan Sun(Department of Digestive Diseases,Hunan Provincial People’s Hospital,Changsha,Hunan,410005,China;Endoscopy center,Hunan Cancer Hospital,234 Tongzipo Road,Changsha,Hunan,410013)

机构地区：[1]湖南省人民医院消化内科,湖南长沙410005 [2]湖南省肿瘤医院内镜中心,湖南长沙410005

出　　处：《生命科学仪器》2020年第1期40-48,共9页Life Science Instruments

基　　金：国家自然科学基金项目(NO:81502114);湖南省科技厅自然科学基金项目(NO:2016JJ3082);湖南省卫生计生委科研项目(NO:B2015-84)。

摘　　要：目的:结直肠癌(colorectal cancer,CRC)是常见消化系统恶性肿瘤之一,目前,其发病率和死亡率日益上升。迄今为止,结直肠癌的确切发病机制尚不清楚,大量文献表明,结直肠癌的发病机制是一个多基因参与的多阶段的过程,故探索检测结直肠癌某些阶段的生物标志物对于提高患者生存率具有重要意义。方法:本研究使用2D-DIGE、MALDI-TOF/TOF MS、免疫组化等方法,构建结直肠癌组织芯片,通过生存分析,来探究PPIA(肽基脯氨酰顺反异构酶A)、YWHAZ(14-3-3蛋白zeta/delta)和GRP78(78kDa葡萄糖调节蛋白前体)的表达水平是否和CRC的发生和发展有关。结果:在本研究中,通过蛋白质组学分析表明,与正常结直肠粘膜相比,结直肠癌中的PPIA、YWHAZ和GRP78蛋白表达上调。在结直肠癌发生的所有阶段(TNM I-IV期),PPIA均显著上调,PPIA表达越高,预后越差(P=0.002)。YWHAZ在I期明显上调,与临床分期呈负相关(T1-2/T3-4,P=0.003),可能是早期CRC的特异性生物标志物。GRP78在第三和第四阶段上调,提示它参与了CRC淋巴结转移和其他远处转移。此外,在CRC患者中PPIA、YWHAZ和GRP78的高表达与低生存期显著相关(分别为P=0.002、0.024和0.010)。结论:阶段生物标志物PPIA、YWHAZ和GRP78与结直肠癌的发生有显著关系,这些蛋白可能是结直肠癌的潜在预后指标。Objective:This study was to investigate the clinicopathologic significance and prognostic role of stage-associated biomarkers in colorectal cancer(CRC).Methods:Stage-associated biomarkers were identified by comparing the expression of protein between CRC TNM stages I-IV and normal controls with proteomics analysis.After verified by immunohistochemistry(IHC)in CRC tissue microarray,we further analysis the correlation of the biomarkers expression and clinicopathological,as well as its relationship with prognosis.Results:Our proteomic analysis suggests that PPIA(peptidyl-prolyl cis-trans isomerase A)YWHAZ(14-3-3 protein zeta/delta)and GRP78(78-kDa glucose-regulated protein precursor)proteins are up-regulated in CRC compared with non-cancerous colorectal mucosa.PPIA was significantly up-regulated in all stages of CRC carcinogenesis(TNM stages I-IV),and the higher the PPIA expression is,the worse the prognosis(P=0.002).YWHAZ was found to be remarkably up-regulated in stage I and negatively correlated with clinical stages(T1-2/T3-4,P=0.003),so it may be a specific biomarker for early CRC.GRP78 was found to be up-regulated in stages III and IV,suggesting that it participates in CRC lymph node metastasis and other distant metastasis.In addition,the higher expression of PPIA,YWHAZ and GRP78 in CRC patients was significant associated with poor OS(P=0.002,0.024 and 0.010,respectively).Conclusions:These results suggest that the biomarkers PPIA,YWHAZ and GRP78 have significance relationship with CRC carcinogenesis,and that these proteins may represent potential prognostic indicators for CRC.

关 键 词：结直肠癌 阶段相关生物标志物 蛋白质组学 预后 

分 类 号：Q7[生物学—分子生物学]