文章：

散发性小肠腺癌中Wnt信号通路的深入解析

Insight into the Wnt Pathway in Sporadic Small Bowel Adenocarcinoma

原文发布日期：10 September 2025

DOI: 10.3390/cancers17182965

类型: Article

开放获取: 是

英文摘要：

Background/Objectives: The Wnt signaling pathway is pivotal in the adenoma–carcinoma sequence; however, its role in small bowel adenocarcinoma (SBA) remains insufficiently characterized. We analyzed the clinicopathological significance of Wnt pathway-related gene mutations and the expression of downstream or associated proteins in SBA. Methods: Immunohistochemical staining for β-catenin, cyclin D1, c-Myc, E-cadherin, and Wnt5a was performed in 75 primary SBA surgical specimens. Targeted next-generation sequencing was conducted in 48 of these cases. Results: The genomic alterations in the Wnt pathway were identified asAPC(14.6%) andCTNNB1(8.3%), with no overlap between the two mutations. Aberrant (reduced membranous and/or nuclear) expression of β-catenin was observed in 37% of cases. Cyclin D1 and c-Myc were expressed in 60% and 41% of cases, respectively. Aberrant expression of β-catenin and/or Wnt5a was present in 60% of cases and was correlated with cyclin D1 and c-Myc expression. Mutations inAPCandCTNNB1were found in intestinal- and gastrointestinal-type SBAs, but were absent in gastric-type SBA. In intestinal-type SBA, the mutation frequency ofAPCandCTNNB1was 39%, closely aligning with the 45% aberrant expression of β-catenin. Aberrant expression of β-catenin and/or Wnt5a, a ligand of the noncanonical Wnt pathway, was detected in 60% of cases and showed a correlation with both cyclin D1 and c-Myc expression. Conclusions: These findings suggest that both canonical and noncanonical Wnt pathway-related proteins are involved in SBA carcinogenesis and progression. Notably, the canonical Wnt pathway appears to play a predominant role in intestinal-type SBA.

摘要翻译： 

背景/目的：Wnt信号通路在腺瘤-癌序列中至关重要，但其在小肠腺癌中的作用仍未充分阐明。本研究旨在分析Wnt通路相关基因突变及其下游或相关蛋白表达在小肠腺癌中的临床病理学意义。方法：对75例原发性小肠腺癌手术标本进行β-连环蛋白、细胞周期蛋白D1、c-Myc、E-钙黏蛋白和Wnt5a的免疫组织化学染色。对其中的48例进行了靶向二代测序。结果：Wnt通路基因组变异主要为APC（14.6%）和CTNNB1（8.3%）突变，两种突变无重叠现象。37%的病例出现β-连环蛋白异常表达（膜表达减少和/或核表达）。细胞周期蛋白D1和c-Myc的表达率分别为60%和41%。60%的病例存在β-连环蛋白和/或Wnt5a异常表达，且与细胞周期蛋白D1和c-Myc表达相关。APC和CTNNB1突变仅见于肠型和胃肠型小肠腺癌，胃型中未发现。在肠型小肠腺癌中，APC和CTNNB1突变频率为39%，与β-连环蛋白45%的异常表达率高度吻合。60%的病例检测到经典Wnt通路配体β-连环蛋白和非经典Wnt通路配体Wnt5a的异常表达，且两者均与细胞周期蛋白D1和c-Myc表达相关。结论：这些发现表明经典和非经典Wnt通路相关蛋白均参与小肠腺癌的发生发展。值得注意的是，经典Wnt通路似乎在肠型小肠腺癌中发挥主导作用。

原文链接：

Insight into the Wnt Pathway in Sporadic Small Bowel Adenocarcinoma