Zheng Wei, Ju Wei, Yang Xi-Hu, Yan Zhi-Xin
Department of Burns and Plastic Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
Front Oncol. 2023 Jul 13;13:1113604. doi: 10.3389/fonc.2023.1113604. eCollection 2023.
The aim of this study was to investigate angiopoietin-2 (Ang-2/ANGPT2) expression and its relationship with lymphangiogenesis and clinicopathological characteristics in cutaneous malignant melanoma (CMM).
Gene expression differences between metastatic melanoma and melanoma in 472 patients from the TCGA database were analyzed. The target gene Ang-2 was screened. A clinical study was conducted to analyze the correlation between Ang-2 expression in CMM and tumor-associated lymphangiogenesis. A total of 42 patients with primary CMM who underwent extended tumor resection procedures at the Affiliated Hospital of Jiangsu University were included in this study. Clinical data (gender, age, lymph node metastasis, Breslow thickness, and clinical stage) were collected. The expression levels of both Ang-2 and lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) proteins were detected by immunohistochemistry (IHC). Lymphatic vascular density (LVD) was counted by using LYVE-1 to label lymphatic endothelial cells (LECs) in peritumoral and intratumoral areas per high-magnification field of view. Statistical analysis was performed using the Pearson correlation test and Student's -test.
Using the TCGA database, it was found that the gene expression level of Ang-2 in 368 cases of metastatic melanoma was significantly higher than that in 104 cases of melanoma . Correlation analysis showed a significant relationship between Ang-2 and LYVE-1, and vascular endothelial growth factor receptor 3(VEGFR3) expression, respectively, in CMM. Moreover, the optimal cutoff value of survival analysis showed that high Ang-2 expression in CMM had a worse prognosis, based on data from the TCGA database. Our research showed that Ang-2 was more highly expressed in the group of patients with lymph node metastasis and in the group of stage 3C-4 patients than in the group of patients with no lymph node metastasis and in the group of stage 0-3B patients. Our research also showed that LVD in the group of patients with lymph node metastasis and in the group of stage 3C-4 patients was significantly higher than that in the group of no lymph node metastasis and in the group of stage 0-3B patients, respectively. Breslow thickness also correlated with Ang-2 expression and LVD. Ang-2 expression was not related to sex or age. Ang-2 expression was obviously correlated with LVD.
An evaluation of Ang-2 expression and LVD can be used to predict the risk of tumor lymphatic metastasis and determine the prognosis of CMM. These results may also provide a new clinical treatment strategy for CMM.
本研究旨在探讨血管生成素-2（Ang-2/ANGPT2）在皮肤恶性黑色素瘤（CMM）中的表达及其与淋巴管生成和临床病理特征的关系。
分析了来自TCGA数据库的472例患者中转移性黑色素瘤和黑色素瘤之间的基因表达差异。筛选出目标基因Ang-2。进行了一项临床研究，以分析CMM中Ang-2表达与肿瘤相关淋巴管生成之间的相关性。本研究纳入了42例在江苏大学附属医院接受扩大肿瘤切除手术的原发性CMM患者。收集了临床资料（性别、年龄、淋巴结转移、Breslow厚度和临床分期）。通过免疫组织化学（IHC）检测Ang-2和淋巴管内皮透明质酸受体-1（LYVE-1）蛋白的表达水平。使用LYVE-1标记每个高倍视野肿瘤周围和肿瘤内区域的淋巴管内皮细胞（LEC），计算淋巴管密度（LVD）。采用Pearson相关检验和Student's -检验进行统计分析。
利用TCGA数据库发现，368例转移性黑色素瘤中Ang-2的基因表达水平显著高于104例黑色素瘤。相关性分析显示，CMM中Ang-2分别与LYVE-1和血管内皮生长因子受体3（VEGFR3）表达之间存在显著关系。此外，生存分析的最佳截断值显示，基于TCGA数据库的数据，CMM中高Ang-2表达预后较差。我们的研究表明，与无淋巴结转移组和0-3B期组患者相比，Ang-2在淋巴结转移组和3C-4期组患者中表达更高。我们的研究还表明，与无淋巴结转移组和0-3B期组患者相比，淋巴结转移组和3C-4期组患者的LVD显著更高。Breslow厚度也与Ang-2表达和LVD相关。Ang-2表达与性别或年龄无关。Ang-2表达与LVD明显相关。
评估Ang-2表达和LVD可用于预测肿瘤淋巴转移风险并确定CMM的预后。这些结果也可能为CMM提供一种新的临床治疗策略。
