AUTHOR=Lin Tong , Peng Wenya , Mai Peipei , Zhang E. , Peng Lisheng 

TITLE=Human Gastric Cancer Stem Cell (GCSC) Markers Are Prognostic Factors Correlated With Immune Infiltration of Gastric Cancer

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2021.626966

DOI=10.3389/fmolb.2021.626966

ISSN=2296-889X

ABSTRACT=<p>The prognosis of patients with gastric cancer (GC) is still unsatisfying. Numerous markers of gastric cancer stem cells (GCSCs) have been identified and were thought to be related to cancer aggressiveness. However, the roles of GCSC markers in GC patients’ prognosis and immune infiltration remain unknown. Expression of GCSC markers was analyzed using Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA). Their associations with clinicopathological parameters were analyzed using UALCAN and LinkedOmics. Alternations and protein expression of GCSC markers were analyzed by cBioPortal and the Human Protein Atlas databases, respectively. The prognostic significance of GCSC markers was evaluated using Kaplan-Meier plotter. Correlations between the expression of GCSC markers and immune infiltration along with biomarkers of tumor-infiltrating immune cells (TIICs) were assessed combined Tumor Immune Estimation Resource and GEPIA. GeneMANIA was used to discover the interactive genes of GCSC markers, and enrichment analysis was performed using Database for Annotation, Visualization, and Integrated Discovery server. We identified six GCSC markers significantly up-expressed in GC, compared with normal stomach tissues. Among them, the overexpression of <italic>ICAM1</italic>, <italic>THY1</italic>, and <italic>CXCR4</italic> significantly indicated adverse, while <italic>EPCAM</italic> indicated beneficial clinicopathological features of GC patients. The up-regulation of <italic>CXCR4</italic> showed unfavorable prognostic significance, whereas <italic>EPCAM</italic> and <italic>TFRC</italic> showed the opposite. The six GCSC markers were all correlated with the infiltration and activation of distinct TIICs. Especially, <italic>ICAM1</italic>, <italic>THY1</italic>, and <italic>CXCR4</italic> showed strongly positive correlations with tumor-associated macrophages. Besides, chemokine, Toll-like receptor, NF-kappa B, and HIF-1 signaling pathways might be involved in the regulation of GCSC markers on cancer development. This study proposed that GCSC markers might be promising targets of GC treatment to weaken cancer stem-like properties and strengthen anticancer immunity.</p>