通过miRNA-mRNA网络挖掘和机器学习鉴定鼻咽癌预后和内分泌代谢的标志物
Identification of markers for predicting prognosis and endocrine metabolism in nasopharyngeal carcinoma by miRNA-mRNA network mining and machine learning.
发表日期：2023
作者：
Xixia Zhang, Xiao Li, Caixia Wang, Shuang Wang, Yuan Zhuang, Bing Liu, Xin Lian
来源：
Frontiers in Endocrinology
摘要：
南部中国和亚洲有较高的鼻咽癌（NPC）发病率，晚期患者的生存率极低。MiRNAs在调节基因表达和癌症治疗靶点中起着关键作用。本研究旨在揭示影响NPC预后和内分泌代谢的关键miRNAs和靶基因。NPC样本的三个数据集（GSE32960，GSE70970和GSE102349）来自Gene Expression Omnibus（GEO）。使用Limma和WGCNA来鉴定关键预后miRNAs。应用12种miRNA工具来研究miRNAs的潜在靶基因（mRNAs）。引入单变量Cox回归和stepAIC来构建风险模型。进行Pearson分析以分析内分泌代谢与风险评分之间的相关性。进行单样本基因集富集分析（ssGSEA），MCP-counter和ESTIMATE进行免疫分析。通过TIDE和SubMap分析预测免疫治疗的反应。两个关键miRNAs（miR-142-3p和miR-93）与NPC预后密切相关。这两个miRNAs在NPC细胞系中的表达失调。筛选出125个关键miRNAs的潜在靶基因，并且它们富集于自噬和有线噬中的通路。确认了五个靶基因（E2F1，KCNJ8，SUCO，HECTD1和KIF23），构建了一个预测模型，用于将患者分为高风险组和低风险组。风险评分与大多数内分泌相关基因和通路呈负相关。低风险组表现出更高的免疫浸润，抗癌反应，更激活的免疫相关通路和对免疫治疗的更高反应性。本研究揭示了两个关键miRNAs对NPC预后的高度贡献。我们通过miRNA-mRNA网络描绘了关键miRNAs与预后mRNAs之间的具体联系。五基因模型在预测NPC预后和内分泌代谢方面的有效性为NPC患者的个体化免疫治疗提供了指导。Copyright © 2023 Zhang, Li, Wang, Wang, Zhuang, Liu and Lian.
Nasopharyngeal cancer (NPC) has a high incidence in Southern China and Asia, and its survival is extremely poor in advanced patients. MiRNAs play critical roles in regulating gene expression and serve as therapeutic targets in cancer. This study sought to disclose key miRNAs and target genes responsible for NPC prognosis and endocrine metabolism.Three datasets (GSE32960, GSE70970, and GSE102349) of NPC samples came from Gene Expression Omnibus (GEO). Limma and WGCNA were applied to identify key prognostic miRNAs. There were 12 types of miRNA tools implemented to study potential target genes (mRNAs) of miRNAs. Univariate Cox regression and stepAIC were introduced to construct risk models. Pearson analysis was conducted to analyze the correlation between endocrine metabolism and RiskScore. Single-sample gene set enrichment analysis (ssGSEA), MCP-counter, and ESTIMATE were performed for immune analysis. The response to immunotherapy was predicted by TIDE and SubMap analyses.Two key miRNAs (miR-142-3p and miR-93) were closely involved in NPC prognosis. The expression of the two miRNAs was dysregulated in NPC cell lines. A total of 125 potential target genes of the key miRNAs were screened, and they were enriched in autophagy and mitophagy pathways. Five target genes (E2F1, KCNJ8, SUCO, HECTD1, and KIF23) were identified to construct a prognostic model, which was used to divide patients into high group and low group. RiskScore was negatively correlated with most endocrine-related genes and pathways. The low-risk group manifested higher immune infiltration, anticancer response, more activated immune-related pathways, and higher response to immunotherapy than the high-risk group.This study revealed two key miRNAs that were highly contributable to NPC prognosis. We delineated the specific links between key miRNAs and prognostic mRNAs with miRNA-mRNA networks. The effectiveness of the five-gene model in predicting NPC prognosis as well as endocrine metabolism provided a guidance for personalized immunotherapy in NPC patients.Copyright © 2023 Zhang, Li, Wang, Wang, Zhuang, Liu and Lian.