Table_1_Novel CircRNAs in Hub ceRNA Axis Regulate Gastric Cancer Prognosis and Microenvironment.XLS

Gastric cancer (GC) is one of the most prevalent malignancies with an unfavorable survival rate. Immunotherapy may contribute to a better prognosis. However, several phase III trials failed. Circular RNA (circRNA) is a novel type of non-coding RNA, plays a vital role in the progression of tumors. The expression and function of circRNA in the GC immune microenvironment remain obscure. In this study, we utilized a bioinformatic analysis to construct a circRNA/microRNA (miRNA)/messenger RNA (mRNA) network involved in the progression and prognosis of GC. CircRNA DYRK1A_017, circRNA FLNA_118, miR-6512-3p, miR-6270-5p, and VCAN were identified as the key molecules in the hub regulatory axis. Dysregulation of this axis contributed to the cancer-associated signaling pathways (epithelial-mesenchymal transition [EMT], Nuclear factor kappa β-Tumor necrosis factor-α (NFκβ-TNFα) signaling, and angiogenesis) and aberrant immune microenvironment (infiltration by tumor associated macrophage, regulatory T cell, and mast cell). More importantly, the immunosuppressive tumor microenvironment may reveal the mechanism of novel circRNAs in tumors and serve as the target of immunotherapy.

胃癌（Gastric cancer, GC）是最常见的恶性肿瘤之一，患者生存率不佳。免疫治疗或可改善患者预后，但多项III期临床试验未能取得成功。环状RNA（Circular RNA, circRNA）是一类新型非编码RNA，在肿瘤进展过程中发挥关键作用。目前，circRNA在胃癌免疫微环境中的表达模式与生物学功能仍不明确。本研究通过生物信息学分析，构建了与胃癌进展及预后相关的circRNA/微小RNA（microRNA, miRNA）/信使RNA（messenger RNA, mRNA）调控网络。研究鉴定出circRNA DYRK1A_017、circRNA FLNA_118、miR-6512-3p、miR-6270-5p及VCAN作为核心调控轴中的关键分子。该调控轴的异常表达可影响肿瘤相关信号通路（上皮间质转化[Epithelial-Mesenchymal Transition, EMT]、核因子κB-肿瘤坏死因子α[Nuclear factor kappa β-Tumor necrosis factor-α, NFκB-TNFα]信号通路及血管生成），并导致免疫微环境紊乱（肿瘤相关巨噬细胞、调节性T细胞及肥大细胞浸润异常）。更为重要的是，免疫抑制性肿瘤微环境可为阐明新型circRNA在肿瘤中的作用机制提供思路，同时可作为免疫治疗的潜在靶点。