Department of Hepatobiliary Surgery, Tangshan Central Hospital, Hebei Province, China.
Department of Otolaryngology, Qian 'an People's Hospital, Hebei Province, China.
Medicine (Baltimore). 2024 Feb 2;103(5):e35859. doi: 10.1097/MD.0000000000035859.
This study aimed to determine the potential mechanisms through which long noncoding (Lnc) RNA cancer susceptibility candidate 15 (CASC15) affects hepatocellular carcinoma (HCC). We retrieved HCC RNA-seq and clinical information from the UCSC Xena database. The differential expression (DE) of CASC15 was detected. Overall survival was analyzed using Kaplan-Meier (K-M) curves. Molecular function and signaling pathways affected by CASC15 were determined using Gene Set Enrichment Analysis. Associations between CASC15 and the HCC microenvironment were investigated using immuno-infiltration assays. A differential CASC15-miRNA-mRNA network and HCC-specific CASC15-miRNA-mRNA ceRNA network were constructed. The overexpression of CASC15 in HCC tissues was associated with histological grade, clinical stage, pathological T stage, poor survival, more complex immune cell components, and 12 immune checkpoints. We identified 27 DE miRNAs and 270 DE mRNAs in the differential CASC15-miRNA-mRNA network, and 10 key genes that were enriched in 12 cancer-related signaling pathways. Extraction of the HCC-specific CASC15-miRNA-mRNA network revealed that IGF1R, MET, and KRAS were associated with HCC progression and occurrence. Our bioinformatic findings confirmed that CASC15 is a promising prognostic biomarker for HCC, and elevated levels in HCC are associated with the tumor microenvironment. We also constructed a disease-specific CASC15-miRNA-mRNA regulatory ceRNA network that provides a new perspective for the precise indexing of patients with elevated levels of CASC15.
本研究旨在确定长链非编码 (Lnc) RNA 癌症易感性候选基因 15 (CASC15) 影响肝细胞癌 (HCC) 的潜在机制。我们从 UCSC Xena 数据库中检索了 HCC RNA-seq 和临床信息。检测 CASC15 的差异表达 (DE)。使用 Kaplan-Meier (K-M) 曲线分析总生存期。使用基因集富集分析确定 CASC15 影响的分子功能和信号通路。使用免疫浸润测定法研究 CASC15 与 HCC 微环境之间的关联。构建差异 CASC15-miRNA-mRNA 网络和 HCC 特异性 CASC15-miRNA-mRNA ceRNA 网络。HCC 组织中 CASC15 的过表达与组织学分级、临床分期、病理 T 分期、不良预后、更复杂的免疫细胞成分和 12 个免疫检查点有关。我们在差异 CASC15-miRNA-mRNA 网络中鉴定出 27 个 DE miRNAs 和 270 个 DE mRNAs,以及在 12 个癌症相关信号通路中富集的 10 个关键基因。提取 HCC 特异性 CASC15-miRNA-mRNA 网络显示 IGF1R、MET 和 KRAS 与 HCC 进展和发生有关。我们的生物信息学发现证实 CASC15 是 HCC 有前途的预后生物标志物,HCC 中的高水平与肿瘤微环境有关。我们还构建了疾病特异性 CASC15-miRNA-mRNA 调节 ceRNA 网络,为精确标记 CASC15 水平升高的患者提供了新视角。