基于生物信息学方法挖掘调控肾透明细胞癌发生的分子生物标志物

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ABSTRACT：ObjectiveTo identify biomolecular markers closely related to the occurrence of kidney renal clear cell carcinoma （KIRC） and verify their expression levels in clinical samples.MethodsStage Ⅰ KIRC mRNA sequencing data were obtained from The Cancer Genome Atlas （TCGA）.Principal component analysis （PCA） was used for dimensionality reduction to screen differentially expressed genes （DEGs），which then underwent GO and KEGG analyses.Weighted gene co-expression network analysis （WGCNA） was used to screen genes significantly related to KIRC，and a protein-protein interaction （PPI） network was constructed to screen hub genes.The diagnostic value of hub genes was evaluated with receiver operating characteristic （ROC） curve，and their prognostic value was analyzed using survival curve plots.The correlation between the mRNA expressions of hub genes and the pathological stages of KIRC was analyzed.Clinical samples of 20 patients with stage Ⅰ KIRC treated in our hospital were included，and the expressions of the hub genes in cancerous and adjacent tissues were detected with reverse transcription real-time quantitative polymerase chain reaction （RT-qPCR），Western blotting，and enzyme-linked immunosorbent assay （ELISA）.ResultsA total of 8223 DEGs were screened out，including 4092 up-regulated ones and 4131 down-regulated ones.GO analysis showed that DEGs were related to bioadhesion，plasma membrane composition，and transporter activity.KEGG analysis showed that DEGs were related to pathways such as cell adhesion molecules，cytokine-cytokine receptor interactions，and interactions between viral proteins and cytokines and cytokine receptors.WGCNA analysis obtained 171 genes that were significantly related to stage Ⅰ KIRC.The hub gene，lymphocyte cytosolic protein 2 （LCP2），screened out by the PPI network，was significantly related to stage Ⅰ KIRC.The area under the ROC curve was 0.96.The expression level was negatively correlated with the overall survival rate of patients.The expression of LCP2 was related to the stage and lymph node metastasis.Clinical verification showed that the mRNA and protein relative expressions of LCP2 in KIRC tissues were significantly higher than those in adjacent tissues （P＜0.000 1）.ConclusionLCP2 is significantly up-regulated in stage Ⅰ KIRC tissues and can be used as a potential biomarker for the early diagnosis and treatment of KIRC.

摘要：目的采用生物信息学分析筛选与肾透明细胞癌（KIRC）发生密切相关的分子生物标志物，并验证其在临床样本中的表达水平。（剩余11703字）