Abstract
Tumor microenvironment (TME) has been demonstrated to exhibit a regulatory effect on the progressions of gastric cancer (GC). However, the related functions of stromal and immune components (TME-associated genes) in TME remain largely unclear. From the TCGA dataset, we downloaded the clinical data of 375 GC cases and then estimated the percentage of tumor-infiltrating immunocytes (TICs) and the levels of immune and stromal constituents by the use of CIBERSORT and ESTIMATE tolls. Univariate assays were applied to study the differentially expressed genes. The associations between the clinical information of GC patients and the expressions of the specific genes were analyzed based on the TCGA datasets. The effect of Plexin domain containing 2 (PLXDC2) expression on TICs was conducted. We observed that PLXDC2 expression was distinctly upregulated in GC specimens compared with nontumor gastric specimens. Its upregulation was associated with advanced clinical stages and predicted a shorter overall survival of GC patients. The genes in the group of higher expressing PLXDC2 were primarily enriched in immunity-associated events. By the use of CIBERSORT, we observed that PLXDC2 expressions were related to the proportion of dendritic cells resting, T cell CD4 memory resting, eosinophils, mastocyte resting, mononuclear cells, plasma cells, T cell follicle helper, macrophage M2, and dendritic cells activated. Overall, our discoveries revealed that the expression of PLXDC2 was remarkable in GC, might be a possible biomarker for GC, and provided novel contents regarding immune infiltrates, offering novel insight for treatments of GC.
Highlights
Gastric cancer (GC) is the 2nd most common cause of tumor-associated morality and the 4th most commonly seen tumor across the globe [1, 2]
The results showed that T cell CD4 memory resting, eosinophils, macrophage M2, mastocyte resting, mononuclear cells, and dendritic cell resting of highly expressed group of Plexin domain containing 2 (PLXDC2) was remarkably greater in contrast to the low expressing group of PLXDC2; the plasma cells, T cell follicle helper, and dendritic cells stimulated of highlyexpressed group of PLXDC2 was remarkably lower in contrast to the low expressing group of PLXDC2 (Figure 8(a))
To demonstrate the levels of PLXDC2 in GC patients, we collected performed RT-PCR, finding that PLXDC2 expression was distinctly increased in GC specimens compared with matched nontumor specimens (Figure 9(a))
Summary
Gastric cancer (GC) is the 2nd most common cause of tumor-associated morality and the 4th most commonly seen tumor across the globe [1, 2]. Despite the fact that gastroscope has facilitated the decrease of such diseases via allowing early detection of GC, the majority of sufferers are confirmed at late period and exhibit inferior prognostic results [4, 5]. The TNM stage was employed as a marker to forecast the prognostic results of sufferers, and recently, researchers have evidenced that merely the standards are not adequate enough to estimate prognostic results [6, 7]. The progression of tumors is considered to be a sophisticated process involving various noncell and cell constituents in the tumor microenvironment (TME) [8]. TME serves as an essential component in tumor developments, which contains nonmalignance cells like bone marrowderived cells, extracellular matrix, endotheliocytes and adventitial cells, tumor-related fibroblasts, and immunocytes and inflammation cells [9, 10].
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