组织芯片检测肝肠钙粘连蛋白在肝癌组织中的表达及临床意义

邱实; 董卫国; 杨子荣; 张吉翔

组织芯片检测肝肠钙粘连蛋白在肝癌组织中的表达及临床意义

武汉大学人民医院消化科

基金项目:

中央高校基本科研业务费专项资金资助(20103020101000197)；

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中图分类号: R735.7
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出版历程
- 出版日期: 2013-01-20

Differential expression of liver-intestine cadherin in hepatocellular carcinoma and its clinical significance

Research funding:

摘要

摘要:
目的研究肝肠钙粘连蛋白（LI-cadherin）在肝癌组织中的表达以及与肝癌的发生发展和临床病理特征之间的相关性。方法采用免疫组织化学SP法检测70例不同类型肝癌组织和5例正常肝组织标本中LI-cadherin的表达情况,并结合临床资料和相关病理参数进行统计分析。结果 70例肝癌组织中LI-cadherin阳性表达39例,总阳性率为55.7%,5例正常肝组织中未见阳性表达;LI-cadherin的表达与年龄、性别、肿瘤分化程度以及有无远处转移无关（P>0.05）,而与淋巴结转移及血管侵犯密切相关（P<0.05）。结论 LI-cadherin的表达与肝癌的发生、转移和浸润有关,LI-cadherin可能成为诊断肝癌发生、转移及临床分期的新生物学标志物,对于提高临床治疗效果具有指导意义。
- 糖蛋白类 /
- 肝肿瘤 /
- 芯片分析技术
Abstract:
Objective To investigate the expression of liver-intestine (LI) -cadherin in hepatocellular carcinoma (HCC) by tissue microarray and explore its relationship with pathologic features of HCC patients.Methods Seventy primary HCC resection samples with different indexing and five primary normal tissue samples were assessed by tissue microarray and immunohistochemistry based on the SP method.The detected expression levels of LI-cadherin were compared to the clinic pathologic parameters of the tissue donors.Results LI-cadherin expression was detected in 39 (55.7%) of the 70 primary HCC tissues, and none of the normal tissues.Positivity for LI-cadherin expression was significantly associated with lymph node metastasis and venous invasion (both P<0.05) but="" no="" significant="" association="" was="" observed="" with="" tumor="" or="" metastasis="" all="" p="">0.05) .Conclusion LI-cadherin expression may be associated with HCC occurrence, tumor invasion, and metastasis.Future studies should assess the potential of LI-cadherin expression as a diagnostic biomarker or target of molecular therapy for HCC.
- glycoproteins /
- liver neoplasms /
- microchip analytical procedures

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肝细胞癌（HCC）是临床常见的恶性肿瘤之一。HCC早期治疗以手术切除为主，但侵袭性HCC的治疗策略目前选择有限，索拉非尼、仑伐替尼及程序性细胞死亡受体1及其配体免疫抑制剂治疗HCC的效果不佳，临床有效率不足30%。因此，亟需进一步探究HCC的发病机制与治疗靶点。随着基因组学研究的发展，对HCC肿瘤生物学的认识逐渐深入，但HCC的泛素化特征尚不明晰。本研究旨在揭示HCC的泛素化特征，并探寻可指导侵袭性HCC临床诊断和治疗的潜在生物标志物。

陆军军医大学第一附属医院（重庆西南医院）谢传明教授、张雷达教授与重庆医科大学侯宇教授等通过对85例HCC患者肿瘤及相邻正常肝组织进行蛋白质组学、磷酸化修饰组学和泛素化修饰组学测序与分析发现，COL4A1、LAMC1和LAMA4在无病生存期较差患者中高表达。磷酸化与泛素化修饰在代谢和转移相关信号通路中存在关联。利用泛素化组学和蛋白质组学数据对HCC进行分子分型，发现具有不同临床特征的3个亚型：S-‍Ⅰ、S-‍Ⅱ和S-Ⅲ。S-‍Ⅰ亚型以代谢相关蛋白高表达为特征，预后最好；S-Ⅲ亚型与增殖/转移信号通路密切相关，预后最差，表现为总生存期最短和复发率最高；而S-‍Ⅱ亚型则介于两者之间。研究发现，生物标志物TUBA1A、BHMT2、BHMT和ACY1的表达表现出不同的泛素化水平，与HCC患者预后不良密切相关，表明靶向这些蛋白质或其泛素化修饰蛋白可能对临床治疗有益。此外，研究证实TUBA1A K370去泛素化可驱动HCC发生与转移，这主要归因于AKT介导的USP14激活。TUBA1A K370去泛素化标志着一类高侵袭性HCC亚型。值得注意的是，靶向AKT-USP14-TUBA1A复合物可促进TUBA1A降解，并在体内阻断HCC发生。

总之，本研究从泛素化组学、磷酸化组学和蛋白质组学角度对HCC进行了全面的整合分析，该研究不仅加深了对HCC中泛素化特征的了解，并为开发新的HCC生物标志物和潜在的治疗靶点提供了依据。

摘译自LIN XT, LUO YD, MAO C, et al. Integrated ubiquitomics characterization of hepatocellular carcinomas[J]. Hepatology, 2024. DOI: 10.1097/HEP.0000000000001096. [Online ahead of print]

(陆军军医大学第一附属医院肝胆外科谢传明报道）

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