Clinical significance of MUC13 in pancreatic ductal adenocarcinoma.

Clinical significance of MUC13 in pancreatic ductal adenocarcinoma.
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MUC13在胰腺导管腺癌中的临床意义。

DOI:
10.1016/j.hpb.2017.12.003
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发表时间:
2018-06
期刊:
HPB : the official journal of the International Hepato Pancreato Biliary Association
影响因子:
--
通讯作者:
Chauhan SC
Chauhan SC
中科院分区:
其他
文献类型:
--
作者:
Khan S;Zafar N;Khan SS;Setua S;Behrman SW;Stiles ZE;Yallapu MM;Sahay P;Ghimire H;Ise T;Nagata S;Wang L;Wan JY;Pradhan P;Jaggi M;Chauhan SC

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胰腺癌(PanCa)预后不良与缺乏有效的早期诊断生物标志物有关。这项研究阐明了MUC 13作为PanCa的诊断/预后标志物的意义。使用我们内部产生的抗MUC 13小鼠单克隆抗体评估组织中的MUC 13,并通过免疫组织化学、免疫印迹、RT-PCR、计算和亚微米尺度质量密度波动分析、ROC和Kaplan Meir曲线分析来分析临床相关性。胰腺上皮内瘤变(PanIN)病变中100%检测到MUC 13表达(平均综合评分:MCS=5.8; AUC >0.8,P<0.0001),94.6%的胰腺导管腺癌(PDAC)样本(MCS=9.7,P<0.0001)与癌旁组织中的低表达相比(MCS=4,P<0.001),正常胰腺组织中沿着有微弱或无表达(MCS=0.8; AUC >0.8; P<0.0001)。核MUC 13表达与淋巴结转移(P<0.05)、癌细胞向周围组织的浸润(P<0.5)和患者生存率差(P<0.05;预后AUC=0.9)呈正相关。亚微米尺度质量密度和基于人工智能的算法分析还阐明了MUC 13与更大的形态学紊乱(P<0.001)的关联,并且核MUC 13是癌症侵袭性和患者存活率差的强预测因子。本研究提供了关于PanCa样本中MUC 13表达/亚细胞定位的重要信息,并支持使用抗MUC 13 MAb开发PanCa诊断/预后检测。
Poor prognosis of pancreatic cancer (PanCa) is associated with lack of an effective early diagnostic biomarker. This study elucidates significance of MUC13, as a diagnostic/prognostic marker of PanCa. MUC13 was assessed in tissues using our in-house generated anti-MUC13 mouse monoclonal antibody and analyzed for clinical correlation by immunohistochemistry, immunoblotting, RT-PCR, computational and submicron scale mass-density fluctuation analyses, ROC and Kaplan Meir curve analyses. MUC13 expression was detected in 100% pancreatic intraepithelial neoplasia (PanIN) lesions (Mean composite score: MCS=5.8; AUC >0.8, P<0.0001), 94.6% of pancreatic ductal adenocarcinoma (PDAC) samples (MCS=9.7, P<0.0001) as compared to low expression in tumor adjacent tissues (MCS=4, P<0.001) along with faint or no expression in normal pancreatic tissues (MCS=0.8; AUC >0.8; P<0.0001). Nuclear MUC13 expression positively correlated with nodal metastasis (P<0.05), invasion of cancer to peripheral tissues (P<0.5) and poor patient survival (P<0.05; prognostic AUC=0.9). Submicron scale mass density and artificial intelligence based algorithm analyses also elucidated association of MUC13 with greater morphological disorder (P<0.001) and nuclear MUC13 as strong predictor for cancer aggressiveness and poor patient survival. This study provides significant information regarding MUC13 expression/subcellular localization in PanCa samples and supporting the use anti-MUC13 MAb for the development of PanCa diagnostic/prognostic test.
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