消化道泛癌中BGN的表达水平及其意义分析

Analysis of BGN Expression Levels and Their Significance in Pan-Gastrointestinal Cancer

摘要: 目的：系统分析双糖链蛋白聚糖(Biglycan, BGN)在消化道肿瘤中的表达特征。方法：通过整合多中心高通量转录组测序数据，系统分析BGN在消化道泛癌(食管癌(Esophageal Cancer, ESCA)、胃癌(Gastric Cancer, GC)、结直肠癌(Colorectal Cancer, CRC))中的表达模式；采用成簇规律间隔短回文重复序列(Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR)基因敲除技术评估BGN缺失对消化道泛癌细胞生长的影响；结合癌症基因组变异分析和生存分析方法评估BGN突变的临床意义。运用单细胞测序(single-cell RNA sequencing, scRNA-seq)技术解析BGN在消化道肿瘤免疫微环境中的作用；通过免疫浸润反卷积算法分析BGN表达与免疫细胞浸润数量的关联性。采用功能富集分析方法探究BGN在消化道肿瘤连续谱中的作用机制及相关信号通路。结果：BGN mRNA在消化道泛癌中均呈现统一的上调表达模式：食管癌标准化均值差(Standardized Mean Difference, SMD)为2.49 (95% CI: 2.31~2.67, p < 0.01)、胃癌SMD为1.60 (95% CI: 1.50~1.69, p < 0.01)、结直肠癌SMD为1.34 (95% CI: 1.26~1.42, p < 0.01)，呈现从上消化道到下消化道的梯度表达特征。敲除BGN后，消化道泛癌细胞系增殖均受到抑制，显示BGN在消化道肿瘤系统中的统一促癌作用。消化道泛癌中均存在BGN高频率突变，以扩增为主。在免疫微环境层面，BGN在消化道不同部位肿瘤的微环境细胞中均有表达，与CD8⁺ T细胞、中性粒细胞和巨噬细胞的浸润数量呈正相关。富集分析显示，BGN相关基因主要富集于细胞周期、DNA复制等肿瘤共性通路，体现了消化道肿瘤的共同生物学特征。结论：BGN可能通过统一的分子机制在消化道泛癌中发挥促癌作用。

Abstract: Objective: To systematically analyze the expression characteristics of Biglycan (BGN) in gastrointestinal tumors. Methods: By integrating multi-center high-throughput transcriptomic sequencing data, we systematically analyzed BGN expression patterns in pan-gastrointestinal cancers (Esophageal Cancer (ESCA), Gastric Cancer (GC), and Colorectal Cancer (CRC)). Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) gene knockout technology was employed to evaluate the impact of BGN deficiency on pan-gastrointestinal cancer cell growth. Cancer genomic variation analysis, combined with survival analysis methods, was used to assess the clinical significance of BGN mutations. Single-cell sequencing (scRNA-seq) technology was utilized to elucidate the role of BGN in the gastrointestinal tumor immune microenvironment. The association between BGN expression and immune cell infiltration levels was analyzed through immune infiltration deconvolution algorithms. Functional enrichment analysis methods were adopted to explore BGN’s mechanisms of action and related signaling pathways across the gastrointestinal tumor spectrum. Results: BGN mRNA exhibited a unified upregulated expression pattern across pan-gastrointestinal cancers: esophageal cancer showed a Standardized Mean Difference (SMD) of 2.49 (95% CI: 2.31~2.67, p < 0.01), gastric cancer showed an SMD of 1.60 (95% CI: 1.50~1.69, p < 0.01), and colorectal cancer showed an SMD of 1.34 (95% CI: 1.26~1.42, p < 0.01), demonstrating a gradient expression pattern from the upper to lower gastrointestinal tract. Following BGN knockout, proliferation was inhibited in all pan-gastrointestinal cancer cell lines, indicating BGN’s unified oncogenic role across the gastrointestinal tumor system. High-frequency BGN mutations were present in all pan-gastrointestinal cancers, predominantly amplifications. At the immune microenvironment level, BGN was expressed in microenvironmental cells across different gastrointestinal tumor sites and showed positive correlations with CD8⁺ T cell, neutrophil, and macrophage infiltration levels. Enrichment analysis revealed that BGN-related genes were primarily enriched in tumor-associated pathways such as cell cycle and DNA replication, reflecting common biological characteristics of gastrointestinal tumors. Conclusion: BGN may exert oncogenic effects in pan-gastrointestinal cancers through unified molecular mechanisms.