摘要： 目的·分析线粒体核糖体蛋白L12（mitochondrial ribosomal protein L12，
MRPL12）在肺腺癌（lung adenocarcinoma，LUAD）和正常组织中的表达差异和对患者预后的影响，以及预测其生物学功能。方法·利用肿瘤浸润性免疫细胞分析数据库TIMER和GEPIA（gene expression profiling and interactive analyses）交互式网站服务器分析癌症基因组图谱（The Cancer Genome Atlas，TCGA）中
MRPL12在不同癌组织中的表达情况的影响。利用Sangerbox生物信息分析平台对
MRPL12差异表达的癌症类型进行Cox回归和Kaplan-Meier生存分析，评估风险比（hazard ratio，
HR）、95%置信区间（confidence interval，
CI）和Log-rank
P值。采用UALCAN数据分析平台评估MRPL12蛋白表达与临床病理参数的关系。使用LinkedOmics数据库筛选与
MRPL12表达相关的基因。采用DAVID数据库进行京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）通路富集分析。定量聚合酶链反应验证
MRPL12在细胞中的转录水平。结果·
MRPL12在多种癌组织中显著高表达，但只有在LUAD中
MRPL12的高表达与患者较差的总体生存期（overall suivival，OS）和疾病特异性生存期（disease-specific survival，DSS）相关；肿瘤分级程度越高的LUAD患者MRPL12蛋白表达水平越高；在LUAD基因表达数据集中与
MRPL12负相关的基因富集到癌症通路（
P=0.000）、癌症蛋白聚糖（
P=0.000）、非小细胞肺癌（
P=0.000）等癌症相关的通路。
MRPL12在LUAD细胞（H1395、H1975和HCC827）中的mRNA表达水平高于正常细胞（Beas-2B），差异有统计学意义（
P<0.05）。结论·
MRPL12高表达的LUAD患者可能预后较差；
MRPL12可以作为LUAD预后不良的潜在生物标志物和潜在的治疗新靶点。
关键词: 肺腺癌, 线粒体核糖体蛋白L12, 生存分析, 预后, 生物标志物, 治疗靶点 Abstract: Objective·To analyze the difference of expression of mitochondrial ribosomal protein L12 (MRPL12) in lung adenocarcinoma (LUAD) and normal tissues and its influence on the prognosis of patients, and predict its biological function.
Methods·The expressions of MRPL12 in different cancer tissues were analyzed by The Cancer Genome Atlas (TCGA) using the tumor-infiltrating immune cell analysis database TIMER and GEPIA (gene expression profiling and interactive analyses) server. The expressions of MRPL12 in different types of cancer were analyzed by Sangerbox bioinformatics platform. Cox regression and Kaplan-Meier survival analysis were used and the hazard ratios (HR), the 95% confidence intervals (CI) and the Log-rank P values were evaluated. The LinkedOmics database was used to identify the genes associated with MRPL12 expression. The DAVID database was used for the enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The transcription levels of MRPL12 in cells were verified by quantitative PCR (qPCR).
Results·MRPL12 was highly expressed in many cancer types. But only the LUAD patients with high MRPL12 expression had lower overall survival (OS) and disease-specific survival (DSS). The expression of MRPL12 protein increased with tumor stage and individual tumor grade. The genes negatively related to MRPL12 were enriched into several cancer-related pathways in LUAD gene expression data set, including pathways in cancer (P=0.000), proteoglycans in cancer (P=0.000) and non-small cell lung cancer (P=0.000). The mRNA expression levels of MRPL12 in the LUAD cells (H1395, H1975 and HCC827) were higher than that in the normal cell (Beas-2B), and the difference was statistically significant (P<0.05).
Conclusion·The LUAD patients with high expression of MRPL12 may have poor prognosis, and thus MRPL12 can be a potential biomarker and potential therapeutic target for LUAD.
Key words: lung adenocarcinoma (LUAD), mitochondrial ribosomal protein L12 (MRPL12), survival analysis, prognosis, biomarker, therapeutic target PDF全文下载地址:
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