PDF(Pubmed)
Abstract：
Esophageal squamous cell carcinoma (ESCC) has a dismal prognosis because of atypical early symptoms and heterogeneous therapeutic responses. 5-methylcytosine (m5C) modification plays an important role in the onset and development of many tumors and is widespread in long non-coding RNA (lncRNA) transcripts. However, the functions of m5C and lncRNAs in ESCC have not been completely elucidated. Herein, this study aimed to explore the role of m5C-related lncRNAs in ESCC. The RNA-seq transcriptome profiles and clinical information were downloaded from the TCGA-ESCC database. Pearson analysis was used to identify m5C-related lncRNAs. Then we established the m5C-related lncRNAs prognostic signature (m5C-LPS) using univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analysis. Then, the prognostic value of m5C-LPS was evaluated internally and externally using the TCGA-ESCC and GSE53622 databases through multiple methods. We also detected the expression of these lncRNAs in ESCC cell lines and patient tissues. Fluorescence in situ hybridization (FISH) was used to detect the prognostic value of specific lncRNA. In addition, clinical parameters, immune status, genomic variants, oncogenic pathways, enrichment pathways, and therapeutic response features associated with m5C-LPS were explored using bioinformatics methods. We constructed and validated a prognostic signature based on 9 m5C-related lncRNAs (AC002091.2, AC009275.1, CAHM, LINC02057.1, AC0006329.1, AC037459.3, AC064807.1, ATP2B1-AS1, and UBAC2-AS1). The quantitative real-time polymerase chain reaction (qRT-PCR) revealed that most lncRNAs were upregulated in ESCC cell lines and patient tissues. And AC002091.2 was validated to have significant prognostic value in ESCC patients. A composite nomogram was generated to facilitate clinical practice by integrating this signature with the N stage. Besides, patients in the low-risk group were characterized by good clinical outcomes, favorable immune status, and low oncogenic alteration. Function enrichment analysis indicated that the risk score was associated with mRNA splicing, ncRNA processing, and DNA damage repair response. At the same time, we found significant differences in the responses to chemoradiotherapy between the two groups, proving the value of m5C-LPS in treatment decision-making in ESCC. This study established a novel prognostic signature based on 9 m5C-related lncRNAs, which is a promising biomarker for predicting clinical outcomes and therapeutic response in ESCC.
摘要：
食管鳞状细胞癌（ESCC）由于非典型的早期症状和异质性的治疗反应而预后不良。5-甲基胞嘧啶（m5C）修饰在许多肿瘤的发生和发展中起着重要作用，并且广泛存在于长链非编码RNA（lncRNA）转录物中。然而,m5C和lncRNAs在ESCC中的功能尚未完全阐明。在这里，本研究旨在探讨m5C相关lncRNAs在ESCC中的作用。从TCGA-ESCC数据库下载RNA-seq转录组谱和临床信息。Pearson分析用于鉴定m5C相关的lncRNAs。然后我们使用单变量Cox和最小绝对收缩和选择算子（LASSO）回归分析建立了m5C相关的lncRNAs预后特征（m5C-LPS）。然后，m5C-LPS的预后价值通过多种方法使用TCGA-ESCC和GSE53622数据库进行内部和外部评估.我们还检测到这些lncRNAs在ESCC细胞系和患者组织中的表达。荧光原位杂交（FISH）用于检测特定lncRNA的预后价值。此外,临床参数,免疫状态，基因组变异，致癌途径，富集途径，使用生物信息学方法探索与m5C-LPS相关的治疗反应特征。我们基于9个m5C相关的lncRNAs构建并验证了预后特征（AC002091.2，AC009275.1，CAHM，LINC02057.1、AC0006329.1、AC037459.3、AC064807.1、ATP2B1-AS1和UBAC2-AS1)。定量实时聚合酶链反应（qRT-PCR）显示，大多数lncRNA在ESCC细胞系和患者组织中上调。AC002091.2在ESCC患者中具有显著的预后价值。通过将该特征与N阶段整合来生成复合列线图以促进临床实践。此外,低风险组患者的临床预后良好,良好的免疫状态，和低致癌改变。功能富集分析表明，风险评分与mRNA剪接有关，ncRNA处理，和DNA损伤修复反应。同时,我们发现两组之间对放化疗的反应存在显着差异，证明m5C-LPS在ESCC治疗决策中的价值。本研究基于9个m5C相关的lncRNAs建立了一个新的预后特征，这是预测ESCC临床结果和治疗反应的有前途的生物标志物。
