Yu Lan, Mao Xu, Wu Shiwu, Zhou Lei, Song Wenqing, Gong Xiaomeng, Wang Danna
Department of Pathology, The First Affiliated Hospital of Bengbu Medical University Anhui, China.
Department of Pathology, Bengbu Medical University Anhui, China.
Int J Clin Exp Pathol. 2019 Jan 1;12(1):327-336. eCollection 2019.
Recurrence and metastasis are the most common reasons for the treatment failure of epithelial ovarian carcinoma (EOC). WW domain-containing oxidoreductase (WWOX) is a tumor suppressor, which causes down- or lost-expression and is able to promote cell infiltration and progression in several human malignant tumors. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), an important marker of cancer stem cells (CSCs), has been considered a useful biomarker of tumor metastasis and patient prognosis. Vasohibin-1 (VASH1), also known as angiogenesis inhibiting protein-1, can be used as a biological marker for early infiltration and metastasis in many cancers. However, the correlations of WWOX, LGR5, and vasohibin-1 in EOC are still unclear. In this study, we analyzed the relationships of these three markers, as well as their respective correlations with clinicopathological characteristics, to determine whether they are useful biomarkers for the improvement and prognosis of EOC patients.
The positive rates of WWOX, LGR5, and vasohibin-1 in 210 whole tissue samples of EOC were detected by immunohistochemistry. Clinical data was also collected.
The expressions of LGR5 and vasohibin-1 were significantly higher in EOC tissues than the levels in benign ovary tumors. However, WWOX expression was significantly lower in EOC tissues than the levels in benign ovary tumors. The investigation of the associations between WWOX, or LGR5, or vasohibin-1 positive rates with the clinicopathological characteristics of EOC showed associations between the positive rates of each with grade of tumor, lymph node metastasis (LNM), implantation, and International Federation of Gynecology and Obstetrics (FIGO) stage. The overall survival (OS) time of patients with LGR5-positive or vasohibin-1-positive EOC tissues was significantly shorter than that of those who were negative. On the contrary, the OS time of patients with WWOX-positive EOC tissues was significantly higher than the OS time of those who were negative. Importantly, a multivariate analysis indicated that the high level of WWOX, LGR5, and vasohibin-1, as well as implantation, LNM and FIGO stage could be independent prognostic biomarkers for OS in EOC patients.
The expressions of WWOX, LGR5, and vasohibin-1 may represent useful promising biomarkers for metastasis and prognosis, as well as potential therapeutic targets in EOC.
复发和转移是上皮性卵巢癌（EOC）治疗失败的最常见原因。含WW结构域的氧化还原酶（WWOX）是一种肿瘤抑制因子，在多种人类恶性肿瘤中其表达降低或缺失，并能促进细胞浸润和进展。富含亮氨酸重复序列的G蛋白偶联受体5（LGR5）是癌症干细胞（CSCs）的重要标志物，被认为是肿瘤转移和患者预后的有用生物标志物。血管抑制素-1（VASH1），也称为血管生成抑制蛋白-1，可作为多种癌症早期浸润和转移的生物标志物。然而，WWOX、LGR5和血管抑制素-1在EOC中的相关性仍不清楚。在本研究中，我们分析了这三种标志物之间的关系，以及它们各自与临床病理特征的相关性，以确定它们是否是改善EOC患者预后的有用生物标志物。
采用免疫组织化学法检测210例EOC全组织样本中WWOX、LGR5和血管抑制素-1的阳性率，并收集临床资料。
EOC组织中LGR5和血管抑制素-1的表达明显高于良性卵巢肿瘤。然而，EOC组织中WWOX的表达明显低于良性卵巢肿瘤。对WWOX、LGR5或血管抑制素-1阳性率与EOC临床病理特征之间的相关性研究表明，每种标志物的阳性率与肿瘤分级、淋巴结转移（LNM）、种植转移以及国际妇产科联盟（FIGO）分期之间均存在相关性。LGR5阳性或血管抑制素-1阳性EOC组织患者的总生存（OS）时间明显短于阴性患者。相反，WWOX阳性EOC组织患者的OS时间明显高于阴性患者。重要的是，多因素分析表明，WWOX、LGR5和血管抑制素-1的高水平表达，以及种植转移、LNM和FIGO分期可能是EOC患者OS的独立预后生物标志物。
WWOX、LGR5和血管抑制素-1的表达可能是EOC转移和预后的有用生物标志物，以及潜在的治疗靶点。
