Comprehensive analysis of PHGDH for predicting prognosis and immunotherapy response in patients with endometrial carcinoma

BMC Medical Genomics

Research

Yunkai Xie¹  He Zhang¹  Xiaoling Zhao¹  Shuning Chen¹  Dan Luo¹  Weimin Kong¹ 

[1] Department of Gynecological Oncology, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, 100006, Beijing, China;

关键词: PHGDH;    Endometrial carcinoma;    TCGA;    Bioinformatics;    Immune infiltrates;   

DOI  :  10.1186/s12920-023-01463-5

 received in 2022-10-27, accepted in 2023-02-16,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundPHGDH (Phosphoglycerate Dehydrogenase) is the first branch enzyme in the serine biosynthetic pathway and plays a vital role in several cancers. However, little is known about the clinical significance of PHGDH in endometrial cancer.MethodsClinicopathological data of endometrial cancer were downloaded from the Cancer Genome Atlas database (TCGA). First, the expression of PHGDH in pan-cancer was investigated, as well as the expression and prognostic value of PHGDH in endometrial cancer. The effect of PHGDH expression on the prognosis of endometrial cancer was analyzed by Kaplan-Meier plotter and Cox regression. The relationship between PHGDH expression and clinical characteristics of endometrial cancer was investigated by logistic regression. Receiver operating characteristic (ROC) curves and nomograms were developed. Possible cellular mechanisms were explored using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, the Gene Ontology (GO), and gene set enrichment analysis (GSEA). Finally, TIMER and CIBERSORT were used to analyze the relationship between PHGDH expression and immune infiltration. CellMiner™ was used to analyze the drug sensitivity of PHGDH.ResultsThe results showed that PHGDH expression was significantly higher in endometrial cancer tissues than in normal tissues at mRNA and protein levels. Kaplan-Meier survival curves showed that patients in the high expression group had shorter overall survival (OS) and disease free survival (DFS) than patients in the low PHGDH expression group. Multifactorial COX regression analysis further supported that high PHGDH expression was an independent risk factor associated with prognosis in patients with endometrial cancer. The results showed estrogen response, mTOR, K-RAS, and epithelial mesenchymal transition (EMT) were differentially elevated in the high-expression group of the PHGDH group. CIBERSORT analysis showed that PHGDH expression is related to the infiltration of multiple immune cells. When PHGDH is highly expressed, the number of CD8+T cells decreases.ConclusionPHGDH plays a vital role in the development of endometrial cancer, which is related to tumor immune infiltration, and can be used as an independent diagnostic and prognostic marker for endometrial cancer.

【 授权许可】

CC BY   
© The Author(s) 2023

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