骨肉瘤组织差异表达基因筛选及其与患者预后的关系

Screening out differentially expressed genes in osteosarcoma and its relationship with the prognosis

目的采用生物信息学的方法筛选骨肉瘤组织差异表达基因,并探讨其与患者预后的关系。方法收集骨肉瘤组织及其配对癌旁正常组织标本各4例份,采用转录组测序技术筛选两种组织中的差异表达基因,并进行基因本体(GO)功能显著性富集分析。在癌症和肿瘤基因图谱骨肉瘤数据库中选择258例份骨肉瘤组织标本,采用Kaplan-Meier曲线分析富集于生物学过程的差异表达基因对患者生存时间的影响。结果骨肉瘤及其癌旁正常组织存在差异表达基因875个,其中表达上调的基因346个、表达下调的基因529个。GO功能显著性富集分析共识别出14个有意义的类型;在6个生物学过程类型中,差异表达基因主要富集于外源性代谢过程、细胞黏附、细胞外基质组成、类固醇代谢过程等;在8个细胞成分类型中,差异表达基因主要富集于细胞外体、细胞外空间、胶原三聚体、核小体等。258例份骨肉瘤组织中,还原酶1(NQO1)基因高表达233例份、低表达25例份,NQO1基因高表达、低表达患者生存时间分别为(2 763±15)、(1 568±13)d,二者比较P<0.01;醛脱氢酶3族A1(ALDH3A1)基因高表达233例份、低表达25例份,ALDH3A1基因高表达、低表达患者生存时间分别为(2 725±11)、(1 421±14)d,二者比较P<0.01;其余基因表达情况对患者的生存时间均无明显影响(P均>0.05)。结论采用生物信息学的方法筛选出骨肉瘤组织差异表达基因875个,主要富集于生物学过程和细胞成分类型;其中NQO1、ALDH3A1基因低表达提示患者预后不良。

To screen out the differentially expressed genes in osteosarcoma tissues by bioinformatics and to investigate its relationship with the prognosis of patients. Methods We performed RNA-Seq to screen out the differentially expressed genes（ DEGs） in osteosarcoma and matched normal tissues of four osteosarcoma patients followed by the Gene Oncology（ GO） enrichment. In addition,we selected 258 cases of osteosarcoma tissue specimens in the Cancer Genome Atlas（ TCGA） HCC data to analyze the influence of DEGs on survival time of patients by using based on Kaplan-Meier curve analysis. Results In total,875 DEGs were identified in four pairs of osteosarcoma specimens,including down-regulated 529 genes and 346 up-regulated genes. According to GO enrichment,14 significant GO terms in the biological process were identified. In the six biological process types,the DEGs were mainly enriched in exogenous metabolic processes,cell adhesion,extracellular matrix composition,and steroid metabolism process; in the 8 cell composition types,the DEGs were mainly enriched in the extracellular domain,extracellular space,collagen trimer,nucleosome and so on. Two novel genes（ NQO1 and ALDH3A1） were significantly associated with poor prognosis in the TCGA osteosarcoma cohort（ n = 258）.The average survival time in 233 cases with over-expression and 25 cases with low-expression of NQO1 was（ 2763 ± 15）and（ 1568 ± 13） days,respectively. The average survival time in 233 cases with over-expression and 25 cases with low-expression of ALDH3A1 was（ 2725 ± 11） and（ 1421 ± 14） days,respectively. The expression of other genes had no significant effect on the survival time of the patients（ all P 〉0. 05）. Conclusion We identified 875 DEGs that mainly enrich in biological process and cellular component and the low-expression of NQO1 and ALDH3A1 is significantly associated with poor prognosis for osteosarcoma.