VGLL3 is a prognostic biomarker and correlated with clinical pathologic features and immune infiltrates in stomach adenocarcinoma

Abstract

Due to its poor clinical outcome, there is an urgent need to identify novel prognostic markers for stomach adenocarcinoma (STAD). Here, we aimed to explore the relationship between VGLL3 expression and clinico-pathological features, dendritic cells, macrophages, and prognosis of STAD. VGLL3 expression levels were significantly associated with histological grade, T stage, and TNM stage. VGLL3 levels and patient's age were also independent prognostic factors of the clinical outcome of STAD. In addition, VGLL3 was associated with the abundance of macrophages and dendritic cells in tumor infiltrates, of which only VGLL3 and macrophage counts were the independent prognostic factors of immune cell infiltration in the TIMER Database. Extracellular matrix receptor interaction, focal adhesion, pathways in cancer, MAPK, JAK STAT, and WNT signaling pathways were enriched in VGLL3 high-expressing datasets as determined by Gene Set Enrichment Analysis (GSEA), while DNA replication, glyoxylate, and dicarboxylate metabolism, glutathione metabolism, homologous recombination, and glycosylphosphatidylinositol gpi banchor biosynthesis were enriched in VGLL3 low-expressing datasets. Thus, VGLL3 is a novel prognostic biomarker of both the clinical outcome and immune infiltration in STAD, and may therefore be a promising therapeutic target.Despite advances in treatment modalities, gastric cancer remains the most common cause of cancer-related deaths in Asia, and the second most common cause of death worldwide 1 . Around 90% to 95% of gastric cancer cases involve stomach adenocarcinomas (STAD) 2 . Although the survival of STAD patients has greatly improved in the past 20 years due to surgery, chemotherapy and targeted therapy, the prognosis is still unsatisfactory 3 . Poor differentiation, late diagnosis, lack of predictive markers, and ineffective therapeutic targets are key factors that drive STAD metastasis and recurrence 4 . Therefore, it is essential to explore the molecular mechanisms underlying STAD development and progression to identify novel prognostic biomarkers and potential therapeutic targets to treat gastric cancer.Transcription cofactor vestigial-like protein 3 (VGLL3) is a coactivator of mammalian toxicity equivalency factors (TEFs), and was associated with breast cancer, colon cancer, and lung cancer among other malignancies 5-9 . In our previous study, we found that VGLL3 at the protein level as determined by immunohistochemistry (IHC) was a novel prognostic biomarker for gastric cancer in the Chinese population 10 . However, its role at the mRNA level of STAD and immune microenvironment remains to be elucidated. To determine whether VGLL3 was involved in the progression of STAD, the Wilcox test and Kruskal test method were used to analyze the differences in VGLL3 expression in subgroups of clinic-pathological trait. Cox regression and log-rank test were used to evaluate significance of VGLL3 on disease prognosis.Recently, more and more evidence showed immune cell infiltration plays a vital role in predicting overall...

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