Chen Qiuxiang, Du Xiaojing
Department of Ultrasound, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Department of Gastroenterology, Minhang Hospital, Fudan University, Shanghai, China.
Front Genet. 2022 Aug 29;13:948102. doi: 10.3389/fgene.2022.948102. eCollection 2022.
Fibroblast growth factor (FGF) and its receptor (FGFR) play crucial roles in gastric cancer (GC). Long non-coding RNAs (lncRNAs) are defined as RNA molecules of around 200 nucleotides or more, which are not translated into proteins. As well-known regulatory factors, lncRNAs are considered as biomarkers for prognosis and treatment response in GC. It is of importance to identify FGF/FGFR-related lncRNAs in GC. Here, some FGF/FGFR-related lncRNAs were identified in GC based on the data from public databases, the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Then a four-lncRNAs (, , , and ) risk score (RS) model was established for predicting GC's prognosis by using Cox analysis. According to the median value of RS, GC patients were divided into low and high RS group. Low RS group displayed high tumor mutation burden and infiltration of immune cells, as well as more sensitivity to immunotherapy or chemotherapy. High RS group showed high infiltration of stromal cells and more oncogenic signatures. In addition, a comprehensive analysis was carried out and found that high RS group may exhibit specific sensitivity to Panobinostat (histone deacetylases inhibitor) and Tivantinib (MET inhibitor). In summary, our study not only offers a novel personalized prognostication classification model according to FGF/FGFR-related lncRNAs, but also provides a new strategy for subclass-specific precision treatment in GC.
成纤维细胞生长因子（FGF）及其受体（FGFR）在胃癌（GC）中发挥着关键作用。长链非编码RNA（lncRNAs）被定义为长度约200个核苷酸或更长的RNA分子，它们不会被翻译成蛋白质。作为众所周知的调控因子，lncRNAs被认为是GC预后和治疗反应的生物标志物。在GC中鉴定FGF/FGFR相关的lncRNAs具有重要意义。在此，基于来自公共数据库、癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）的数据，在GC中鉴定了一些FGF/FGFR相关的lncRNAs。然后，通过Cox分析建立了一个四lncRNAs（、、和）风险评分（RS）模型来预测GC的预后。根据RS的中位数，将GC患者分为低RS组和高RS组。低RS组显示出高肿瘤突变负担和免疫细胞浸润，以及对免疫治疗或化疗更敏感。高RS组显示出基质细胞的高浸润和更多的致癌特征。此外，进行了综合分析，发现高RS组可能对帕比司他（组蛋白去乙酰化酶抑制剂）和替凡替尼（MET抑制剂）表现出特异性敏感性。总之，我们的研究不仅根据FGF/FGFR相关的lncRNAs提供了一种新的个性化预后分类模型，还为GC中的亚类特异性精准治疗提供了新策略。
