Huang Zhihao, He Aoxiao, Wang Jiakun, Lu Hongcheng, Xu Xiaoyun, Zhang Rongguiyi, Liao Wenjun, Feng Qian, Wu Linquan
Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Department of General Surgery, Jinxian People's Hospital, Nanchang, Jiangxi, China.
Cancer Biomark. 2022;34(1):77-93. doi: 10.3233/CBM-210354.
Toll-like receptors participate in various biological mechanisms, mainly including the immune response and inflammatory response. Nevertheless, the role of TLRs in STAD remains unclear.
We aimed to explore the expression, prognosis performance of TLRs in STAD and their relationship with immune infiltration.
Student's t-test was used to evaluate the expression of TLRs between STAD tissues and normal tissues. Kaplan-Meier method was applied to explored the prognosis value of TLRs in STAD. And qRT-PCR validated their expression and prognosis value. Spearman's correlation analysis and Wilcoxon rank-sum test were used to assess the association between TLRs and immune infiltration in STAD.
The mRNA level of TLR3 was downregulated in STAD. We summarized genetic mutations and CNV alteration of TLRs in STAD cohort. Prognosis analysis revealed that STAD patients with high TLR3 expression showed better prognosis in OS, FP and PPS. The result of qRT-PCR suggested that TLR3 expression was decreased in STAD tissues and STAD patients with high TLR3 mRNA level had a better OS. Univariate and multivariate cox regression analysis suggested TLR3 expression and clinical stage as independent factors affecting STAD patients' prognosis. A positive association existed between TLR3 expression and the abundance of immune cells and the expression of various immune biomarkers. Furthermore, key targets related to TLR3 were identified in STAD, mainly including MIR-129 (GCAAAAA), PLK1, and V$IRF1_01.
Our result demonstrated TLR3 as a prognosis marker and associated with immune infiltration in STAD.
Toll样受体参与多种生物学机制,主要包括免疫反应和炎症反应。然而,TLRs在胃癌(STAD)中的作用仍不清楚。
我们旨在探讨TLRs在STAD中的表达、预后表现及其与免疫浸润的关系。
采用学生t检验评估STAD组织与正常组织中TLRs的表达。应用Kaplan-Meier法探讨TLRs在STAD中的预后价值。qRT-PCR验证了它们的表达和预后价值。采用Spearman相关分析和Wilcoxon秩和检验评估TLRs与STAD免疫浸润之间的关联。
STAD中TLR3的mRNA水平下调。我们总结了STAD队列中TLRs的基因突变和拷贝数变异(CNV)改变。预后分析显示,TLR3高表达的STAD患者在总生存期(OS)、无进展生存期(FP)和无进展生存期(PPS)方面预后较好。qRT-PCR结果表明,STAD组织中TLR3表达降低,TLR3 mRNA水平高的STAD患者OS较好。单因素和多因素cox回归分析表明,TLR3表达和临床分期是影响STAD患者预后的独立因素。TLR3表达与免疫细胞丰度及各种免疫生物标志物的表达呈正相关。此外,在STAD中鉴定出与TLR3相关的关键靶点,主要包括MIR-129(GCAAAAA)、PLK1和V$IRF1_01。
我们的结果表明TLR3是一种预后标志物,与STAD中的免疫浸润相关。