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Serum proteome profiling reveals SOX3 as a candidate prognostic marker for gastric cancer

机译:血清蛋白质组分析显示SOX3可作为胃癌的预后标志物

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摘要

Searching for the novel tumour biomarkers is pressing for gastric cancer diagnostication and prognostication. The serum specimens from patients diagnosed with locally advanced gastric carcinoma before operation and 4 week after surgery were collected, respectively, and serum proteome profiling was conducted by liquid chromatography–mass spectrometry (MS)/MS. Fifty‐five proteins were identified to be up‐regulated and 16 proteins were down‐regulated, and these differentially expressed proteins participated in various biological processes. Serum levels of SOX3, one of down‐regulated proteins, in stomach cancer patients were higher than in healthy controls. SOX3 levels in cancer tissues were remarkably related to tumour differentiation, lymph node metastasis, primary tumour invasion and pTNM (pathological TNM) stage. Analysis with The Cancer Genome Atlas database indicated that SOX3 level and pTNM stage were the independent risk factors for the patient survival and that the overall survival was negatively associated with the SOX3 levels. Loss‐of‐function showed that SOX3 promoted gastric cancer cell invasion and migration in vitro and in vivo. SOX3 silence inhibits the expression of MMP9, and SOX3 is responsible for MMP9 expression transcriptionally. Our study highlights the potentiality of the paired pre‐ and post‐operation serum proteome signatures for the detection of biomarkers and reveals that SOX3 may serve as a candidate prognosis marker for gastric cancer.
机译:寻找新的肿瘤生物标志物正迫切需要胃癌的诊断和预后。分别收集术前和术后4周被诊断为局部晚期胃癌的患者的血清标本,并通过液相色谱-质谱(MS)/ MS进行血清蛋白质组分析。鉴定出55种蛋白质被上调,而16种蛋白质被下调,这些差异表达的蛋白质参与了各种生物学过程。胃癌患者的血清SOX3(一种被下调的蛋白质)水平高于健康对照组。癌症组织中的SOX3水平与肿瘤分化,淋巴结转移,原发肿瘤浸润和pTNM(病理TNM)阶段显着相关。癌症基因组图谱数据库的分析表明,SOX3水平和pTNM分期是患者生存的独立危险因素,而总体生存与SOX3水平呈负相关。功能丧失表明SOX3在体外和体内均可促进胃癌细胞的侵袭和迁移。 SOX3沉默抑制MMP9的表达,而SOX3负责转录MMP9的表达。我们的研究突出了配对的术前和术后血清蛋白质组特征对检测生物标志物的潜力,并揭示了SOX3可以作为胃癌的候选预后标志物。

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