Identification of a novel 10 immune‐related genes signature as a prognostic biomarker panel for gastric cancer

Abstract Background In recent years, immunotherapy has developed rapidly and has gradually become one of the important methods for treatment of gastric cancer. The research on immune cells and immune-related genes in the tumor microenvironment greatly encourages the development of immunotherapy. Methods : The devolution algorithm (CIBERSORT) was applied to infer the proportion of 22 immune infiltrating cells based on gene expression profiles of gastric cancer tissue, which were downloaded from TCGA and GEO databases. The TCGA database was utilized to analyze the differential expression of immune-related genes, and explore the potential molecular functions of these genes.ResultsWe have observed the enrichment of multiple immune cells in the microenvironment of gastric cancer. Some of these cells are closely related to Fuhrman grade and TNM staging. Survival analysis showed that the infiltration level of CD8 + T cells, activated CD4 + memory T cells and M2 macrophages was significantly related to the prognosis of gastric cancer patients. The functional enrichment analysis of immune-related genes revealed that these genes were mainly associated with cytokine activation and response. Four significant modules were screened by PPI network and 20 key genes were screened from the modules, and the expression levels of CALCR and PTH1R are strikingly related to the prognosis of gastric cancer patients.ConclusionsThe type and number of infiltrating immune cells in the microenvironment of gastric cancer, as well as immune-related genes are closely related to tumor progression, and can be used as important indicators for patient prognosis assessment.

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PI3K/AKT/β-Catenin Signaling Regulates Vestigial-Like 1 Which Predicts Poor Prognosis and Enhances Malignant Phenotype in Gastric Cancer

Cancers ◽

10.3390/cancers11121923 ◽

2019 ◽

Vol 11 (12) ◽

pp. 1923 ◽

Cited By ~ 4

Author(s):

Bo-Kyung Kim ◽

Jae-Ho Cheong ◽

Joo-Young Im ◽

Hyun Seung Ban ◽

Seon-Kyu Kim ◽

...

Keyword(s):

Gastric Cancer ◽

Target Genes ◽

Prognostic Biomarker ◽

Xenograft Model ◽

Gastric Cancer Cells ◽

Metastatic Lesions ◽

Proliferation And Metastasis ◽

Cancer Tissues ◽

Sphere Formation

Although gastric cancer is a common cause of cancer mortality worldwide, its biological heterogeneity limits the available therapeutic options. Therefore, identifying novel therapeutic targets for developing effective targeted therapy of gastric cancer is a pressing need. Here, we investigate molecular function and regulatory mechanisms of Vestigial-like 1 (VGLL1) in gastric cancer. Microarray analysis of 556 gastric cancer tissues revealed that VGLL1 was a prognostic biomarker that correlated with PI3KCA and PI3KCB. VGLL1 regulates the proliferation of gastric cancer cells, as shown in live cell imaging, sphere formation, and in vivo xenograft model. Tail vein injection of NUGC3 cells expressing shVGLL1 resulted in less lung metastasis occurring when compared to the control. In contrast, larger metastatic lesions in lung and liver were detected in the VGLL1-overexpressing NUGC3 cell xenograft excision mouse model. Importantly, VGLL1 expression is transcriptionally regulated by the PI3K-AKT-β-catenin pathway. Subsequently, MMP9, a key molecule in gastric cancer, was explored as one of target genes that were transcribed by VGLL1-TEAD4 complex, a component of the transcription factor. Taken together, PI3K/AKT/β-catenin signaling regulates the transcription of VGLL1, which promotes the proliferation and metastasis in gastric cancer. This finding suggests VGLL1 as a novel prognostic biomarker and a potential therapeutic target.

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