A novel liver metastasis-correlated protein of pancreatic neuroendocrine neoplasm (PanNEN) discovered by proteomic analysis.
A novel liver metastasis-correlated protein of pancreatic neuroendocrine neoplasm (PanNEN) discovered by proteomic analysis.
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DOI：
10.18632/oncotarget.25110
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发表时间：
2018-05-11
期刊：
影响因子：
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通讯作者：
Unno M
中科院分区：
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作者：
Shimura M;Mizuma M;Takadate T;Katoh Y;Suzuki T;Iseki M;Hata T;Aoki S;Suzuki Y;Sakata N;Ohtsuka H;Hayashi H;Morikawa T;Nakagawa K;Motoi F;Naitoh T;Igarashi K;Sasano H;Unno M
本研究的目的是通过蛋白质组学方法寻找新的肝转移相关蛋白Pannen，以比较胰腺癌(PT)和配对转移性肝肿瘤(LT)。应用蛋白质组学方法对118例Pannen手术病例中7例福尔马林固定石蜡包埋(FFPE)的PT和配对LT组织进行了分析。激光捕获显微切割法选择性采集FFPE组织中的肿瘤细胞。通过基于质谱仪的鸟枪分析，从提取的多肽中共检测到3722个蛋白质。通过半定量比较和免疫组织化学证实，筛选出在PT和LT中表达不同的候选蛋白。我们重点研究了ANXA6、CNPY2、RAB11B和TUBB3，它们在LT中都有较高的表达。采用免疫组织化学方法，对所有FFPE标本的肝无复发生存率(RFS)与候选蛋白在PT中的表达进行相关性分析。CNPY2阳性患者的肝脏RFS明显低于CNPY2阴性患者(10年肝脏RFS：39.8%vs.92.3%，p=0.012)。此外，ANXA6阳性患者的肝脏RFS往往比ANXA6阴性患者更差(10年肝脏RFS；51.4%对95.0%，p=0.099)。在多因素分析中，CNPY2阳性(HR：6.19，95%CI：1.47~42.79，P=0.011)和肿瘤大小≥为42 mm(HR：4.63，95%CI：1.03~23.23，P=0.045)是肝RFS的独立预测因素。综上所述，CNPY2是Pannen新的肝转移相关蛋白。
The aim of this study was to identify novel liver metastasis-correlated proteins of PanNEN by proteomics to compare pancreatic tumor (PT) with paired metastatic liver tumor (LT). Of 118 surgical cases with PanNEN, 7 cases with formalin-fixed paraffin-embedded (FFPE) tissues of both PT and paired LT were evaluated by proteomics. Tumor cells were selectively collected from FFPE tissues by laser capture microdissection. A total of 3,722 proteins were detected from extracted peptides by mass spectrometry-based shotgun analysis. Selection of the candidate proteins expressed differently between PT and LT were performed by semi-quantitative comparison in silico and confirmation with immunohistochemistry. We focused on ANXA6, CNPY2, RAB11B and TUBB3, all of which had higher expressions in LT. In all surgical cases with FFPE samples, liver recurrence-free survival (RFS) was evaluated in correlation to the expression of the candidate proteins in PT by immunohistochemistry. Liver RFS was significantly poorer in CNPY2 positive patients than in negative patients (10-year liver RFS; 39.8% vs. 92.3%, p = 0.012). Also, liver RFS tended to be poorer in ANXA6 positive patients than in those who were negative (10-year liver RFS; 51.4% vs. 95.0%, p = 0.099). In the multivariate analysis, the independent predictors of liver RFS were CNPY2 positivity (HR: 6.19, 95 % CI: 1.47–42.79, p = 0.011) and tumor size ≥ 42 mm (HR: 4.63, 95 % CI: 1.03–23.23, p = 0.045). In conclusion, CNPY2 is a novel liver metastasis-correlated protein of PanNEN.