Department of Pathology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, China.
Oxid Med Cell Longev. 2022 Jun 1;2022:2218140. doi: 10.1155/2022/2218140. eCollection 2022.
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.
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.
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.
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.
CXCL 家族是一类通过 G 蛋白偶联受体信号传导的分泌生长因子，异常表达与许多肿瘤的生长和进展有关。然而，其在 Epstein-Barr 病毒（EBV）相关胃癌（EBVaGC）中的预后价值尚未得到充分研究。因此，探索 CXCL 家族在 EBVaGC 中的预后价值具有重要意义。
分析癌症基因组图谱（TCGA）中 STAD 数据的 CXCL 家族 mRNA 表达。Kaplan-Meier Plotter 用于评估 CXCL 家族的预后价值。通过 TFCheckpoint、miRWalk 和 ViRBase 数据库鉴定与 CXCL 家族相关的转录因子（TFs）和 miRNA。使用 GSE51575 数据库评估预后模型。
与 TCGA-STAD 中的正常组织相比，EBVaGC 中 CXCL1/3/5/6/8/9/10/11/16 的 mRNA 表达明显上调，而 CXCL12/14 的表达下调。EBVaGC 中 CXCL9、CXCL10、CXCL11 和 CXCL17 的 mRNA 表达高于 EBVnGC，而 CXCL6、CXCL12 和 CXCL17 的 mRNA 表达低于 EBVnGC。无论肿瘤分期如何，EBVaGC 中 CXCL9、CXCL10 和 CXCL11 的 mRNA 表达水平均高于 EBVnGC。EBVaGC 中高 CXCL8 mRNA 表达与患者的 OS 较好相关，而 EBVnGC 中高 CXCL9 表达与患者的 OS 较好相关。我们获得了 10 个与 CXCL 相关的候选潜在转录因子（TFs）：OTOP3、NKX6-2、NKX2-2、FEV、SMYD1、TRIMSO、TBX10、CDX1、SLC26A3 和 ARC。获得了 576 个 miRNA-mRNA 相互作用。其中，65 个 miRNA 被预测与 CXCL6、CXCL9、CXCL10 和 CXCL11 相关。与 TCGA-STAD 的结果相似，GSE51575 数据集还显示，EBVaGC 组织中 CXCL1/3/9/10/11/16 的 mRNA 表达水平明显高于相应的正常胃黏膜组织，而 CXCL12/14 的 mRNA 表达水平显著降低。与 EBVnGC 组织相比，EBVaGC 组织中 CXCL3/9/10/11/13/17 的 mRNA 表达增加。
CXCL 家族成员的表达差异与 EBVaGC 的进展密切相关。CXCL9/10/11/17 mRNA 的表达可能是 EBVaGC 患者有前途的预后指标。
