Molecular markers for cervical cancer prognosis: a prognostic model using stemness-related lncRNAs and functional analysis of EMX2OS
摘要
Cancer stemness-related long non-coding RNAs (lncRNAs) play a crucial role in tumor initiation and progression. This study aimed to identify stemness-related lncRNAs in cervical cancer (CESC) and evaluate the prognostic significance, clinical relevance, and biological functions.
Materials & methodsTranscriptome data from the Cancer Genome Atlas were used to construct a co-expression network of cancer stemness-related genes and CESC-specific lncRNAs, focusing on cervical squamous cell carcinoma and endocervical adenocarcinoma. Identified stemness-related lncRNAs were used to develop a prognostic model through univariate, LASSO, and multivariate Cox regression analyses. Quantitative real-time PCR and in situ hybridization were performed to measure EMX2OS expression in normal and cancerous cervical tissues. Statistical tests were applied to analyze the association between EMX2OS expression and clinicopathological features. The effects of EMX2OS overexpression on cell proliferation, migration, and invasion were investigated using using the Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2’-deoxyuridine (EdU) assay, plate cloning assay, wound healing assay, and transwell assays.
ResultsA prognostic model comprising five lncRNAs (FOXD3-AS1, KCNMB2-AS1, EMX2OS, LINC02446, SOCS2-AS1) was developed, demonstrating robust prognostic performance. EMX2OS expression was significantly down-regulated in CESC tissues compared to normal tissues. In situ hybridization showed a marked association between EMX2OS expression and tumor size (P = 0.005), depth of stromal invasion (P = 0.009), and 5-year survival status (P = 0.003). The 5-year survival rate was significantly lower in the low expression group (P = 0.006). Overexpression of EMX2OS significantly suppressed cell proliferation, migration, and invasion.
ConclusionsThe prognostic model based on 5 lncRNAs reflecting the stemness of CESC stem cells can reliably predict the prognosis of patients with CESC. Additionally, EMX2OS serves as a significant tumor suppressor marker in CESC.