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Abstract：
Glutamine fructose-6-phosphate aminotransferase 2 (GFPT2) is a rate-limiting enzyme in hexosamine biosynthesis involved in the occurrence and progress of many cancers. What role it plays in gastric cancer (GC) is still unclear. In this study, transcriptome sequencing data from the Harbin Medical University (HMU)-GC cohort and The Cancer Genome Atlas (TCGA) dataset were combined with the HMU-TCGA training cohort to analyze the biological function and clinical significance of GFPT2. The correlation of GFPT2 with immune cells and stromal cells was analyzed in the GC immune microenvironment through transcriptome sequencing data and a public single-cell sequencing database. In cell lines, GC tissues, and the tissue microarray, GFPT2 protein expression was confirmed by western blotting and immunohistochemistry. The mRNA of GFPT2 was highly expressed in the tumor (p < 0.001), and GC cells and tumors expressed high levels of GFPT2 protein. Compared to low expression, high GFPT2 mRNA expression was associated with higher levels of tumor invasion, higher pathological stages, and poor prognosis (p = 0.02) in GC patients. In a drug susceptibility analysis, GFPT2 mRNA expression was associated with multiple chemotherapeutic drug sensitivity, including docetaxel, paclitaxel, and cisplatin. Gene enrichment analysis found that GFPT2 was mainly primarily involved in the extracellular matrix receptor interaction pathway. The ESTIMATE, CIBERSORT, and ssGSEA algorithms showed that GFPT2 was associated with immune cell infiltration. In addition, GFPT2 was more likely to be expressed within cancer-associated fibroblasts (CAFs), and high levels of GFPT2 expression were highly correlated with four CAFs scores (all p < 0.05). Finally, a prognostic model to assess the risk of death in GC patients was constructed based on GFPT2 protein expression and lymph node metastasis rate. In conclusion, GFPT2 plays an essential role in the function of CAFs in GC. It can be used as a biomarker to assess GC prognosis and immune infiltration.
摘要：
谷氨酰胺果糖-6-磷酸氨基转移酶2(GFPT2)是己糖胺生物合成中的限速酶,参与多种癌症的发生和发展。它在胃癌（GC）中起什么作用尚不清楚。在这项研究中,将哈尔滨医科大学（HMU）-GC队列和癌症基因组图谱（TCGA）数据集的转录组测序数据与HMU-TCGA训练队列相结合，分析GFPT2的生物学功能和临床意义。通过转录组测序数据和公共单细胞测序数据库，在GC免疫微环境中分析GFPT2与免疫细胞和基质细胞的相关性。在细胞系中,GC组织，和组织微阵列，通过蛋白质印迹和免疫组织化学证实GFPT2蛋白表达。GFPT2mRNA在肿瘤中高表达(p<0.001),和GC细胞和肿瘤表达高水平的GFPT2蛋白。与低表达相比，高GFPT2mRNA表达与较高水平的肿瘤侵袭相关，病理分期较高，GC患者预后不良（p=0.02）。在药物敏感性分析中，GFPT2mRNA表达与多种化疗药物敏感性相关,包括多西他赛,紫杉醇,和顺铂.基因富集分析发现GFPT2主要参与细胞外基质受体相互作用通路。估计,CIBERSORT,和ssGSEA算法显示GFPT2与免疫细胞浸润有关。此外,GFPT2更有可能在癌症相关成纤维细胞（CAFs）中表达，GFPT2的高水平表达与四个CAFs评分高度相关（均p<0.05）。最后,基于GFPT2蛋白表达和淋巴结转移率,构建了评估GC患者死亡风险的预后模型.总之,GFPT2在GC中CAFs的功能中起重要作用。它可以作为评价GC预后和免疫浸润的生物标志物。
