Prognostic roles of cross-talk between peritumoral hepatocytes and stromal cells in hepatocellular carcinoma involving peritumoral VEGF-C, VEGFR-1 and VEGFR-3.
Prognostic roles of cross-talk between peritumoral hepatocytes and stromal cells in hepatocellular carcinoma involving peritumoral VEGF-C, VEGFR-1 and VEGFR-3.
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瘤周肝细胞和基质细胞之间的串扰在涉及瘤周 VEGF-C、VEGFR-1 和 VEGFR-3 的肝细胞癌中的预后作用
DOI：
10.1371/journal.pone.0064598
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sun HC
中科院分区：
文献类型：
--
作者：
Zhuang PY;Shen J;Zhu XD;Lu L;Wang L;Tang ZY;Sun HC
背景：肿瘤周围肝组织通过血管生成和淋巴管生成相关因子在肝细胞癌（HCC）进展和患者生存中发挥潜在作用。这些因素在肝细胞癌患者根治性切除后肝细胞和基质细胞中的预后作用仍有待探讨。方法收集145例无淋巴结转移（LNM）的肝癌患者和37例有LNM的肝癌患者的肿瘤组织及癌周组织。组织微阵列由来自每个切除标本的肿瘤组织和周围瘤周组织的一式两份核心构建。采用免疫组化和实时荧光聚合酶链反应检测血管内皮生长因子-A（VEGF-A）、VEGF-C、VEGF受体-1（VEGFR-1）、VEGFR-2和VEGFR-3的表达。通过CD 68染色确定巨噬细胞浸润。研究这些因子的表达与总生存期（OS）和复发时间（TTR）之间的相关性。结果VEGF-A、VEGF-C、VEGFR-1、VEGFR-2、VEGFR-3在癌周的表达明显高于癌组织中的表达。VEGFR-1主要定位于瘤周巨噬细胞，而VEGF-C和VEGFR-3主要定位于瘤周肝细胞。肿瘤周围VEGF-C、VEGFR-1和VEGFR-3高表达的HCC与巨噬细胞的肿瘤周围分布（0.87%±0.26% vs 0.45%±0.20%）、LNM（32.4% vs 12.0%）、TTR较短（10.2个月vs 34.5个月）和预后不良（19.4个月vs 49.3个月）相关。结论VEGF-C、VEGFR-1和VEGFR-3在瘤周肝组织中的表达与一种独特类型的HCC相关，这种HCC在肝切除术后预后较差。
Background Peritumoral liver tissue could play a potential role in hepatocellular carcinoma (HCC) progression and patient survival via angiogenesis- and lymphangiogensis-related factors. The prognostic role of these factors in hepatocytes and stromal cells in HCC patients after curative resection remains to be explored. Methods Tumor tissue and surrounding peritumoral tissue were obtained from 145 resected HCC patients without lymph node metastasis (LNM) and 37 resected HCC patients with LNM. Tissue microarrays were constructed from duplicate cores of tumor tissue and surrounding peritumoral tissue from each resected specimen. Immunohistochemistry and real-time polymerase chain reaction were used to evaluate the expression of vascular endothelial growth factor-A (VEGF-A), VEGF-C, VEGF receptor-1(VEGFR-1), VEGFR-2, and VEGFR-3. Macrophage infiltration was determined by CD68 staining. Correlations between the expression of these factors and overall survival (OS) and time to recurrence (TTR) were studied. Results The peritumoral expression of VEGF-A, VEGF-C, VEGFR-1, VEGFR-2, and VEGFR-3 were significantly higher than expression of these factors in tumors. VEGFR-1 was mostly located in peritumoral macrophages, while VEGF-C and VEGFR-3 were mostly located in peritumoral hepatocytes. HCC with high peritumoral co-expression of VEGF-C, VEGFR-1, and VEGFR-3 was associated with higher peritumoral distribution of macrophages (0.87%±0.26% versus 0.45%±0.20%), LNM (32.4% versus 12.0%), shorter TTR (10.2 months versus 34.5 months), and poor prognosis (19.4 months versus 49.3 months). Conclusion Expression of VEGF-C, VEGFR-1, and VEGFR-3 in peritumoral liver tissue is associated with a unique type of HCC that has a poorer outcome after hepatectomy.
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影响因子：
13.5
作者：
Yamaguchi, R;Yano, H;Kojiro, M
通讯作者：
Kojiro, M
影响因子：
8.8
作者：
通讯作者：
--
DOI：
10.1073/pnas.191117498
发表时间：
2001-09-11
影响因子：
11.1
作者：
Dias, S;Hattori, K;Rafii, S
通讯作者：
Rafii, S
DOI：
10.1084/jem.193.6.727
发表时间：
2001-03-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lin EY;Nguyen AV;Russell RG;Pollard JW
通讯作者：
Pollard JW
DOI：
10.1161/atvbaha.107.150433
发表时间：
2008-04-01
影响因子：
8.7
作者：
Murakami, Masato;Zheng, Yujuan;Shibuya, Masabumi
通讯作者：
Shibuya, Masabumi