Association between the expression levels of ADAMTS16 and BMP2 and tumor budding in hepatocellular carcinoma.
Association between the expression levels of ADAMTS16 and BMP2 and tumor budding in hepatocellular carcinoma.
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ADAMTS16和BMP2的表达水平与肝细胞癌中的肿瘤萌芽之间的关联。
DOI：
10.3892/ol.2023.13842
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发表时间：
2023-06
期刊：
影响因子：
2.9
通讯作者：
Liu Y
中科院分区：
文献类型：
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作者：
Jiang D;Xu S;Zhang C;Hu C;Li L;Zhang M;Wu H;Yang D;Liu Y
肿瘤出芽（TB）已成为预测多种类型实体癌恶性程度和预后的关键因素。研究已经调查了肝细胞癌（HCC）中TB的预后价值。然而，其在HCC中的分子机制仍不清楚。据我们所知，本研究是第一个比较TB阳性（TB-pos）和TB阴性HCC组织之间差异表达基因（DEG）的表达。在本研究中，总RNA提取40 HCC组织标本，然后测序。根据基因本体论（GO）功能注释，上调的DEG与胚胎肾脏发育相关的GO术语显著相关，这表明TB过程可能至少部分地模拟胚胎肾脏发育的过程。随后，两个基因，一个去整合素和金属蛋白酶结构域与血小板反应蛋白基序16（ADAMTS 16）和骨形态发生蛋白2（BMP 2），筛选和验证通过免疫组化分析肝癌组织芯片。根据免疫组化结果，ADAMTS 16和BMP 2在TB-pos HCC样品中上调，并且BMP 2在出芽细胞中的表达比肿瘤中心增加。此外，通过细胞培养实验，证明ADAMTS 16和BMP 2可能促进肝癌的TB，从而促进肝癌的恶性进展。进一步分析显示ADAMTS 16表达与坏死和胆汁淤积相关，BMP 2表达与巴塞罗那临床肝癌分期和包裹肿瘤簇的血管相关。总体而言，本研究的结果为HCC中TB的可能机制提供了见解，并揭示了潜在的抗HCC治疗靶点。
Tumor budding (TB) has become a crucial factor for predicting the malignancy grade and prognostic outcome for multiple types of solid cancer. Studies have investigated the prognostic value of TB in hepatocellular carcinoma (HCC). However, its molecular mechanism in HCC remains unclear. To the best of our knowledge, the present study was the first to compare the expression of differentially expressed genes (DEGs) between TB-positive (TB-pos) and TB-negative HCC tissues. In the present study, total RNA was extracted from 40 HCC tissue specimens and then sequenced. According to Gene Ontology (GO) functional annotation, upregulated DEGs were markedly associated with embryonic kidney development-related GO terms, which suggested that the TB process may at least partly mimic the process of embryonic kidney development. Subsequently, two genes, a disintegrin and metalloproteinase domain with thrombospondin motifs 16 (ADAMTS16) and bone morphogenetic protein 2 (BMP2), were screened and verified through immunohistochemical analysis of HCC tissue microarrays. According to the immunohistochemical results, ADAMTS16 and BMP2 were upregulated in TB-pos HCC samples, and BMP2 expression was increased in budding cells compared with the tumor center. Additionally, through cell culture experiments, it was demonstrated that ADAMTS16 and BMP2 may promote TB of liver cancer, thus promoting the malignant progression of liver cancer. Further analysis revealed that ADAMTS16 expression was associated with necrosis and cholestasis, and BMP2 expression was associated with the Barcelona Clinic Liver Cancer stage and the vessels encapsulating tumor clusters. Overall, the findings of the present study provided insights into the possible mechanisms of TB in HCC and revealed potential anti-HCC therapeutic targets.
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影响因子：
4.6
作者：
Baloche V;Rivière J;Tran TBT;Gelin A;Bawa O;Signolle N;Diop MBK;Dessen P;Beq S;David M;Busson P
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影响因子：
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作者：
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通讯作者：
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影响因子：
3.9
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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