识别宫颈癌放化疗敏感性的枢纽基因：一项基于双数据集的计算机分析
Identifying hub genes for chemo-radiotherapy sensitivity in cervical cancer: a bi-dataset in silico analysis.
作者信息
Wang Yanhong, Ouyang Yi, Cao Xinping, Cai Qunrong
机构信息
Department of Radiotherapy, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, Fujian, China.
State Key Laboratory of Oncology in South China, Department of Radiotherapy, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510600, Guangdong, China.
出版信息
Discov Oncol. 2024 Sep 12;15(1):434. doi: 10.1007/s12672-024-01328-y.
PURPOSE
To identify the hub genes that associated with chemo-radiotherapy sensitivity for cervical cancer and to explore the relationship between hub genes and various cellular processes and potential mechanism of cervical cancer.
METHODS
The gene expression data of 21 patients with CESC and the mRNA expression profiles of 296 patients with CESC were obtained from the Gene Expression Omnibus(GEO) and The Cancer Genome Atlas (TCGA) databases, respectively. The potential functions and regulatory mechanisms of differentially expressed genes (DEGs) were identified using GO and KEGG enrichment analyses. Hub genes were identified using random survival forest analysis. The relationship between hub genes and various cellular processes was comprehensively analyzed. The expression of hub genes was assessed using clinical data extracted from the Human Protein Atlas (HPA) database.
RESULTS
A total of 139 and 13 DEGs were found to be upregulated and downregulated, respectively, in CESC. The six hub genes, namely, SELP, PIM2, CCL19, SDS, NRP1, and SF3A2, were significantly correlated with immune cell infiltration, chemotherapy sensitivity, disease-related genes, and enriched signaling pathways (all p-value < 0.05). A nomogram and calibration curve were generated using the six hub genes to predict prognosis with high accuracy. A regulatory network comprising TFs (ZBTB3) and mRNAs (NRP1/PIM2/SELP) and several competitive endogenous RNA (ceRNA) networks comprising mRNAs, miRNAs, and lncRNAs were constructed. Data from HPA indicated that the protein expression of the six hub genes differed significantly between patients with CESC and healthy individuals.
CONCLUSION
Upregulation of SELP, PIM2, CCL19, SDS, NRP1, and SF3A2 is associated with radiotherapy sensitivity and is involved in various cellular processes in CESC. These six genes may serve as biomarkers for predicting the radiotherapy response and prognosis in patients with CESC.
目的
鉴定与宫颈癌放化疗敏感性相关的枢纽基因，并探讨枢纽基因与宫颈癌各种细胞过程之间的关系及潜在机制。
方法
分别从基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）数据库中获取21例宫颈鳞状细胞癌（CESC）患者的基因表达数据和296例CESC患者的mRNA表达谱。使用基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析来鉴定差异表达基因（DEG）的潜在功能和调控机制。使用随机生存森林分析来鉴定枢纽基因。综合分析枢纽基因与各种细胞过程之间的关系。使用从人类蛋白质图谱（HPA）数据库中提取的临床数据评估枢纽基因的表达。
结果
在CESC中，分别发现139个和13个DEG上调和下调。六个枢纽基因，即血小板内皮细胞黏附分子1（SELP）、原癌基因PIM-2（PIM2）、C-C基序趋化因子配体19（CCL19）、短链脱氢酶/还原酶家族成员（SDS）、神经纤毛蛋白1（NRP1）和剪接因子3a亚基2（SF3A2），与免疫细胞浸润、化疗敏感性、疾病相关基因和富集的信号通路显著相关（所有p值<0.05）。使用这六个枢纽基因生成了列线图和校准曲线，以高精度预测预后。构建了一个由转录因子（锌指蛋白3（ZBTB3））和mRNA（NRP1/PIM2/SELP）组成的调控网络，以及几个由mRNA、微小RNA（miRNA）和长链非编码RNA（lncRNA）组成的竞争性内源RNA（ceRNA）网络。HPA的数据表明，CESC患者和健康个体之间六个枢纽基因的蛋白质表达存在显著差异。
结论
SELP、PIM2、CCL19、SDS、NRP1和SF3A2的上调与放疗敏感性相关，并参与CESC的各种细胞过程。这六个基因可作为预测CESC患者放疗反应和预后的生物标志物。
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