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探讨 LGR5 作为肝外胆管癌预后标志物的作用:来自表达分析和临床相关性的见解。

Exploring LGR5 as a prognostic marker of extrahepatic cholangiocarcinoma: insights from expression analysis and clinical correlations.

机构信息

Department of Pathology, Nagano Red Cross Hospital, Nagano, Japan.

Department of Laboratory Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.

出版信息

Diagn Pathol. 2024 Aug 28;19(1):116. doi: 10.1186/s13000-024-01537-7.

Abstract

BACKGROUND

Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) is a cancer stem cell (CSC) marker of colorectal cancer and may be a CSC marker of other cancer types. Few studies have been conducted on LGR5 expression in extrahepatic cholangiocarcinoma (ECC).

METHODS

We analyzed LGR5 expression using RNAscope, a highly sensitive RNA in situ hybridization technique. Fifty-three ECCs were selected from the medical archives at Shinshu University Hospital and analyzed using a tissue microarray. LGR5 expression levels were divided into expression and no expression groups. LGR5 expression and clinicopathological characteristics were analyzed.

RESULTS

Among 25 cases, no LGR5-positive dots were identified. Among 28 cases, some LGR5-positive dots were observed in carcinoma cells, together with a wide range of LGR5-positive cells. LGR5 expression was conspicuous in glandular duct formations. Well- to moderately differentiated types showed significantly higher LGR5 expression than the poorly differentiated type (p = 0.0268). LGR5 expression was associated with good overall survival (p = 0.0219) and good disease-free survival (DFS) (p = 0.0228). High LGR5 expression was associated with well- to moderately-differentiated types, indicating a favorable prognosis. In terms of DFS, multivariate analysis showed that high LGR5 expression was an independent favorable prognostic factor (p = 0.0397).

CONCLUSIONS

These findings suggest that LGR5 is a promising, novel prognostic marker.

摘要

背景

富含亮氨酸重复序列的 G 蛋白偶联受体 5(LGR5)是结直肠癌的癌症干细胞(CSC)标志物,也可能是其他癌症类型的 CSC 标志物。目前关于 LGR5 在肝外胆管癌(ECC)中的表达研究较少。

方法

我们使用高度敏感的 RNA 原位杂交技术 RNAscope 分析了 LGR5 的表达。从信州大学医院的医学档案中选择了 53 例 ECC,并使用组织微阵列进行了分析。根据 LGR5 表达水平将其分为表达组和无表达组。分析 LGR5 表达与临床病理特征的关系。

结果

在 25 例中,未发现 LGR5 阳性点。在 28 例中,在癌细胞中观察到一些 LGR5 阳性点,同时 LGR5 阳性细胞广泛存在。LGR5 表达在腺管形成中较为明显。高分化至中分化类型的 LGR5 表达显著高于低分化类型(p=0.0268)。LGR5 表达与总生存期(p=0.0219)和无病生存期(DFS)(p=0.0228)较好相关。高 LGR5 表达与高分化至中分化类型相关,提示预后良好。在 DFS 方面,多因素分析显示高 LGR5 表达是独立的预后良好因素(p=0.0397)。

结论

这些发现表明 LGR5 是一种有前途的新型预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ee1/11350935/a8107fc513a1/13000_2024_1537_Fig1_HTML.jpg

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