Characterization of the Prognostic Values of CXCL Family in Epstein–Barr Virus Associated Gastric Cancer

Abstract

Background. CXCL family is a class of secreted growth factors signaling through G-protein-coupled receptors, and abnormal expression is associated with the growth and progression of many tumors. However, their prognostic value has been poorly studied in Epstein–Barr virus- (EBV-) associated gastric cancer (EBVaGC). Therefore, it is of great significance to explore the prognostic value of the CXCL family in EBVaGC. Methods. CXCL family mRNA expression was analyzed in STAD data from The Cancer Genome Atlas (TCGA). Kaplan-Meier Plotter was used to assess the prognostic value of the CXCL family. Transcription factors (TFs) and miRNAs associated with the CXCL family were identified by TFCheckpoint, miRWalk, and ViRBase databases. The prognostic model was evaluated using the EBVaGC patient cohort GSE51575. Results. The mRNA expression of CXCL1/3/5/6/8/9/10/11/16 was significantly upregulated, while the expression of CXCL12/14 was downregulated in EBVaGC compared with normal tissues from TCGA-STAD. The mRNA expressions of CXCL9, CXCL10, CXCL11, and CXCL17 in EBVaGCs were higher than those in EBVnGCs, but the mRNA expressions of CXCL6, CXCL12, and CXCL17 were lower than those in EBVnGCs. The mRNA expression levels of CXCL9, CXCL10, and CXCL11 in EBVaGCs were higher than those in EBVnGCs regardless of the tumor stage. High mRNA expression of CXCL8 was associated with better OS in patients with EBVaGC, while high expression of CXCL9 was associated with better OS in patients with EBVnGC. We obtained 10 candidate potential transcription factors (TFs) associated with CXCLs: OTOP3, NKX6-2, NKX2-2, FEV, SMYD1, TRIMSO, TBX10, CDX1, SLC26A3, and ARC. 576 miRNA-mRNA interactions were obtained. Among them, 65 miRNAs were predicted to be correlated with CXCL6, CXCL9, CXCL10, and CXCL11. Similar to the results of TCGA-STAD, the GSE51575 dataset also showed that the mRNA expression levels of CXCL1/3/9/10/11/16 were markedly enhanced in EBVaGC tissues compared with corresponding normal gastric mucosa tissues, while the mRNA expression levels of CXCL12/14 were significantly reduced. The mRNA expression levels of CXCL3/9/10/11/13/17 were increased in EBVaGC compared with EBVnGC tissues. Conclusions. The expression differences of CXCL family members are closely associated with the progression of EBVaGC. Expression of CXCL9/10/11/17 mRNA may be a promising prognostic indicator for EBVaGC patients.

The role of CXCL family members in different diseases

“…Besides, a research of CXCL family related to Epstein-Barr virus (EBV) associated gastric cancer has elucidated that the expression differences of CXCL family members were closely related to the progression of EBV-associated GC, including the relationship with clinical stage, virus infection, prognosis, etc. It was reported that changes in CXCL9, CXCL10, CXCL11 and CXCL17 mRNA expression had potential prognostic values in patients with EBV-associated GC [ 28 ]. Moreover, Zhou et al had discovered that macrophages, which were induced by the secretion of TNF-α from GC cells released CXCL1 and CXCL5.…”

Expression Profiles of Hepatic Immune Response Genes in HEV Infection

“…Similarly, TNFs and interferon receptors facilitate the initiation of cell pathways associated with infections [ 31 , 32 , 33 ]. These genes were previously studied concerning HBV, HCV, liver diseases, and viral-induced cancers [ 34 , 35 , 36 ], but no study showed this gene with expression profiles in HEV infections. The expression of the seven immune response genes CCL2, CCL5, CXCL10, CXCL15, TNF, IFNGR1, and SAMSN1 was evaluated through a real-time PCR.…”

CXCL2 acts as a prognostic biomarker and associated with immune infiltrates in stomach adenocarcinoma

“…Expression of CXCL9/10/11/17 mRNA may be a promising prognostic indicator for Epstein-Barr virus associated STAD patients. [ 16 ] Another study revealed that CXCL9 was positively correlated with a better prognosis for STAD patients. [ 17 ] Moreover, combinations of initial serum ENA78/CXCL5 and SDF-1/CXCL12 can serve as serum biomarker panels to predict the presence and distant metastasis of STAD.…”