Combination of CALR and PDIA3 is a potential prognostic biomarker for non-small cell lung cancer.

Combination of CALR and PDIA3 is a potential prognostic biomarker for non-small cell lung cancer.
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DOI:
10.18632/oncotarget.18547
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发表时间:
2017-11-14
期刊:
影响因子:
--
通讯作者:
Chen ZN
Chen ZN
中科院分区:
其他
文献类型:
--
作者:
Wang K;Li H;Chen R;Zhang Y;Sun XX;Huang W;Bian H;Chen ZN

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基于蛋白质组学的生物标志物发现方法是用于癌症研究的有前途的策略。本研究采用无标记定量蛋白质组学技术和液相色谱-串联质谱/质谱(LC-MS/MS)技术对16例非小细胞肺癌(NSCLC)及其癌旁肺组织进行定量蛋白质组学分析,以鉴定差异表达的蛋白质。在4047个蛋白质中,有91个蛋白质在NSCLC组织中与癌旁肺组织相比有差异表达(倍数变化> 1.5或< 0.67,P < 0.05)。基因本体论(GO)分析、京都基因和基因组百科全书(KEGG)通路分析和独创性通路分析(IPA)显示91个异常蛋白与肿瘤相关的生物学过程有关。我们使用20对样本通过实时PCR和使用5对样本通过western blot证实候选蛋白,钙网蛋白(CALR)和蛋白质二硫键异构酶家族A成员3(PDIA 3)在NSCLC中过表达。PDIA 3与CALR表达高度相关(斯皮尔曼r = 0.345,P = 0.001),两者在A549和H460细胞中共定位,并相互作用。此外,在88个样本的组织芯片中进行的生存分析表明,NSCLC中CALR和PDIA 3的低表达与总生存率低呈正相关。CALR和PDIA 3联合检测可作为一种有效的生物标志物,显著提高NSCLC预后的预测能力(P = 0.023)。我们的研究结果共同为NSCLC预后提供了潜在的生物标志物数据集,特别是CALR和PDIA 3联合表达的预后价值。
Proteomic-based approaches for biomarker discovery are promising strategies used in cancer research. In this study, we performed quantitative proteomic analysis on 16 paired samples of non-small cell lung cancer (NSCLC) and adjacent non-tumor lung tissues using label-free quantitative proteomics and liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS) to identify differentially expressed proteins. A total of 91 proteins were differentially expressed in NSCLC compared with adjacent non-tumor lung tissues among 4047 identified proteins (fold change > 1.5 or < 0.67, P < 0.05). Gene ontology (GO) analysis, Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and ingenuity pathway analysis (IPA) of 91 dysregulated proteins showed that they were related to the cancer-associated biological processes. We confirmed that the candidate proteins, calreticulin (CALR) and protein disulfide isomerase family A member 3 (PDIA3) were overexpressed in NSCLC by real-time PCR using 20 paired samples and western blot using 5 paired samples. PDIA3 expression was highly associated with CALR expression (Spearman r = 0.345, P = 0.001) and they were co-localized and interacted with each other in A549 and H460 cells. Moreover, survival analysis performed in tissue microarray with 88 samples indicated that low expression of both CALR and PDIA3 in NSCLC was positively associated with poor overall survival. Combination of CALR and PDIA3 might serve as an efficient biomarker and improved the prediction of NSCLC prognosis significantly (P = 0.023). Our results collectively provide a potential biomarker dataset for NSCLC prognosis, especially the prognostic value of combined expression of CALR and PDIA3.
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