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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

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. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between m RNA expression of G protein signal regulated protein 2 (GPSM2), glutamine fructose-6-phosphate transaminase 2 (GFPT2), nucleolar small RNA 51 (SNORA51) and clinicopathological features of hepatocellular carcinoma (HCC) tissues and their effects on prognosis. Methods: 60 patients with HCC who were diagnosed and treated with surgical resection in Affiliated Hospital of Inner Mongolia Medical University from January 2017 to December 2018 were selected. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the m RNA expressions of GPSM2, GFPT2and SNORA51 in HCC tissues and paracancer tissues, and the relationship between the m RNA expressions of GPSM2, GFPT2 and SNORA51 and the clinicopathological characteristics of patients with HCC were analyzed. After 3 years of follow-up, Kaplan-Meier survival curve was used to analyze the prognosis of patients with HCC in different groups, and univariate and multivariate Logistic regression was used to analyze the influencing factors of prognosis of patients with HCC. Results: The m RNA expression levels of GPSM2, GFPT2 and SNORA51 in HCC tissues were significantly higher than those in paracancer tissues (P<0.05). The proportion of vascular invasion and TNM stage Ⅲ in the GPSM2 m RNA high expression group, GFPT2 m RNA high expression group and SNORA51mRNA high expression group were significantly higher than those in the GPSM2 m RNA low expression group and GFPT2m RNA low expression group and SNORA51mRNA low expression group (P<0.05) . Kaplan-Meier analysis showed that the 3-year survival rate of GPSM2 m RNA low expression group, GFPT2 m RNA low expression group, SNORA51mRNA low expression group were significantly higher than those in the GPSM2 m RNA high expression group, GFPT2 m RNA high expression group and SNORA51mRNA high expression group (P<0.05). The results of multivariate Logistic regression analysis model showed that vascular invasion, TNM stage Ⅲ, GPSM2 m RNA high expression, GFPT2 m RNA high expression and SNORA51 m RNA high expression were the risk factors for death of patients with HCC (P<0.05). Conclusion: The abnormally high expression of GPSM2, GFPT2 and SNORA51in HCC tissues is associated with clinicopathological features such as vascular invasion and TNM stage, and the high expression of GPSM2, GFPT2 and SNORA51 is a risk factor for death of patients with HCC. [ABSTRACT FROM AUTHOR]

Background: Recently, increasing evidence has suggested that Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) is related to carcinogenesis. However, the potential roles of GFPT2 in colon cancer still need to be fully investigated. Methods: We examined the protein levels of GFPT2 by immunohistochemistry (IHC) in tissues collected from 83 patients with colon cancer. We further detected GFBPT2 protein levels by Western Blot assay. We checked the relationship between GFPT2 expression levels and overall survival (OS), stromal and immune scores and immune components from The Cancer Gene Atlas (TCGA) database. GFBP2-related pathways were validated in the Cancer Cell Line Encyclopedia (CCLE) database. Expression of GFPT2 in single cell subpopulations was calculated from The Tumor Immune Single Cell Center (TISCH). The levels of GFPT2 and drug sensitivity data were performed from CellMiner dataset. Results: GFPT2 was highly expressed and correlated with poor pathological features in 83 colon cancer patients. Moreover, increased GFPT2 expression was significantly associated with poorer OS in 329 colon adenocarcinoma (COAD) patients. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed the differentially expressed genes of GFPT2 were mostly enriched in focal adhesion, ECM receptor interaction, JAK/STAT signaling pathway and immune related pathways. In addition, GFPT2 expression was correlated with the tumor microenvironment (TME). GFPT2 expression was linked to cancer-associated fibroblasts (CAFs)-associated factors and epithelial-mesenchymal transition (EMT)-related factors. GFPT2 was positively correlated with immunosuppressive cells and regulated immunosuppressive factors and T-cell exhaustion. Finally, our data suggested that the expression of GFPT2 may be a judgment of the sensitivity of a certain class of drugs. Conclusions: Our work reveals the roles of GFPT2 in tumorigenesis, particularly in immune response, TME and drug resistance, which are crucial for the development of customized cancer therapies. [ABSTRACT FROM AUTHOR]

BackgroundRecently, increasing evidence has suggested that Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) is related to carcinogenesis. However, the potential roles of GFPT2 in colon cancer still need to be fully investigated.MethodsWe examined the protein levels of GFPT2 by immunohistochemistry (IHC) in tissues collected from 83 patients with colon cancer. We further detected GFBPT2 protein levels by Western Blot assay. We checked the relationship between GFPT2 expression levels and overall survival (OS), stromal and immune scores and immune components from The Cancer Gene Atlas (TCGA) database. GFBP2-related pathways were validated in the Cancer Cell Line Encyclopedia (CCLE) database. Expression of GFPT2 in single cell subpopulations was calculated from The Tumor Immune Single Cell Center (TISCH). The levels of GFPT2 and drug sensitivity data were performed from CellMiner dataset.ResultsGFPT2 was highly expressed and correlated with poor pathological features in 83 colon cancer patients. Moreover, increased GFPT2 expression was significantly associated with poorer OS in 329 colon adenocarcinoma (COAD) patients. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed the differentially expressed genes of GFPT2 were mostly enriched in focal adhesion, ECM receptor interaction, JAK/STAT signaling pathway and immune related pathways. In addition, GFPT2 expression was correlated with the tumor microenvironment (TME). GFPT2 expression was linked to cancer-associated fibroblasts (CAFs)-associated factors and epithelial-mesenchymal transition (EMT)-related factors. GFPT2 was positively correlated with immunosuppressive cells and regulated immunosuppressive factors and T-cell exhaustion. Finally, our data suggested that the expression of GFPT2 may be a judgment of the sensitivity of a certain class of drugs.ConclusionsOur work reveals the roles of GFPT2 in tumorigenesis, particularly in immune response, TME and drug resistance, which are crucial for the development of customized cancer therapies.