Department of General Surgery, Xiangya Hospital of Central South University, Changsha, 410000, Hunan Province, China.
Hunan Key Laboratory of Precise Diagnosis and Treatment of Gastrointestinal Tumor, Xiangya Hospital of Central South University, Changsha, 410000, Hunan Province, China.
World J Surg Oncol. 2022 Apr 7;20(1):110. doi: 10.1186/s12957-022-02561-x.
The B3GNT6 protein is a member of the O-GlcNAc transferase (OGT) family and is responsible for the production of the core 3 structure of O-glycans. It is generally expressed in the gastrointestinal (GI) tract; however, its clinical significance in colorectal cancer remains largely unexplored.
We obtained mRNA transcriptomic sequencing data from 3 gene expression omnibus (GEO) datasets (GSE37182, GSE39582, GSE103512) and The Cancer Genome Atlas (TCGA) to compare the B3GNT6 mRNA levels between colorectal cancer and normal tissues and further evaluate its value as a prognostic marker in colorectal cancer. We further validated this at the protein level in our cohort using immunohistochemical staining of B3GNT6 as well as the Human Protein Atlas online database.
B3GNT6 expression was downregulated in colorectal cancer tissues as compared to that in the normal tissues at both mRNA and protein levels. Downregulation of B3GNT6 expression was found to be associated with poor overall survival in patients with colorectal cancer as per the data in GSE39582 and TCGA databases. Low B3GNT6 mRNA levels were significantly associated with chromosome instability (CIN) and KRAS mutations in patients with colorectal cancer. Gene set enrichment analysis (GSEA) revealed that low B3GNT6 expression levels in colorectal cancer were associated with increased proteasome activity.
The results of this study demonstrate that low expression of B3GNT6 is a potential biomarker for poor outcomes in patients with CRC. Moreover, the low expression of B3GNT6 may indicate more frequent activation of the KRAS/ERK signaling pathway, high CIN, and increased proteasomal activity. These novel findings may prove helpful for molecular diagnosis and provide a new therapeutic target for colorectal cancer.
B3GNT6 蛋白是 O-糖基转移酶（OGT）家族的一员，负责产生 O-聚糖的核心 3 结构。它通常在胃肠道（GI）中表达；然而，其在结直肠癌中的临床意义在很大程度上仍未得到探索。
我们从 3 个基因表达综合（GEO）数据集（GSE37182、GSE39582、GSE103512）和癌症基因组图谱（TCGA）中获得了 mRNA 转录组测序数据，以比较结直肠癌和正常组织之间的 B3GNT6 mRNA 水平，并进一步评估其作为结直肠癌预后标志物的价值。我们使用 B3GNT6 的免疫组织化学染色以及 Human Protein Atlas 在线数据库在我们的队列中进一步验证了这一点。
与正常组织相比，B3GNT6 在结直肠癌组织中的表达在 mRNA 和蛋白质水平上均下调。根据 GSE39582 和 TCGA 数据库中的数据，B3GNT6 表达下调与结直肠癌患者的总生存期不良相关。B3GNT6 mRNA 水平低与结直肠癌患者的染色体不稳定性（CIN）和 KRAS 突变显著相关。基因集富集分析（GSEA）显示，结直肠癌中低 B3GNT6 表达水平与蛋白酶体活性增加相关。
本研究结果表明，B3GNT6 表达水平低可能是 CRC 患者预后不良的潜在生物标志物。此外，B3GNT6 表达水平低可能表明 KRAS/ERK 信号通路更频繁地激活、CIN 更高和蛋白酶体活性增加。这些新发现可能有助于分子诊断，并为结直肠癌提供新的治疗靶点。
