【摘要】 目的 探讨非小细胞肺癌(NSCLC)组织中含Sorbin和SH3结构域的蛋白1(SORBS1)的临床意义及其相关的通路和生物学过程。方法 收集本院2016年1月至2019年12月手术切除的126对NSCLC组织和癌旁组织，采用实时定量PCR(q PCR)检测上述组织的SORBS1水平，分层分析组织SORBS1水平与NSCLC临床病理特征关系，结合随访数据进行生存分析并在Kaplan-Meier Plotter数据库中验证其预后意义。采用Linked Omics数据库对SORBS1的基因本体(GO)及京都基因与基因组百科全书(KEGG)、Panther、Reactome和Wiki通路进行基因集富集分析(GESA)。结果 NSCLC组织的SORBS1水平为0.668±0.036，低于癌旁组织的1.712±0.053(P<0.05)。分层分析发现组织SORBS1水平与TNM分期、肿瘤大小和分化程度有关(P<0.05)，而与性别、年龄、吸烟史、淋巴结转移和病理类型无关(P>0.05)。单因素分析显示TNM分期、肿瘤大小、分化程度和组织SORBS1水平与NSCLC患者的OS有关，其中高水平者的中位OS为57.0个月，优于低水平者的35.0个月，差异有统计学意义(HR=3.033,95%CI:1.632～5.637,P<0.001)，进一步多因素分析发现组织SORBS1水平是OS的危险因素(HR=2.745,95%CI:1.547～5.162,P=0.024)。GO分析结果表明:SORBS1的生物学过程主要富集在的细胞-细胞粘附(GO:0098742)的调控，分子功能的变化主要集中在细胞外基质结构成分(GO:0005201)，细胞成分的变化主要集中在细胞外基质(GO:0031012)。KEGG、Panther、Reactome和Wiki通路分析结果显示:SORBS1富集于细胞粘附分子(hsa04514)、趋化因子和细胞因子信号通路介导的炎症反应(P00031)、细胞外基质组织(R-HSA-1474244)和软骨内骨化(WP474)相关通路。结论SORBS1在NSCLC组织中低表达且与不良预后和恶性进展指标有关，且该基因与细胞外基质相关基因表达及相关信号通路调控关系密切，有望成为NCSLC防治的潜在靶点。更多还原

【Abstract】 Objective To investigate the clinical significance of Sorbin and SH3 domain-containing protein 1( SORBS1) in non-small cell lung cancer( NSCLC) tissues as well as its related pathways and biological processes. Methods One hundred and twenty-six pairs of NSCLC tissues and adjacent tissues surgically resected in our hospital from January 2016 to December 2019 were collected. Real-time quantitative PCR( q PCR) was used to detect the SORBS1 level of the above tissues. Relationship between the SORBS1 level and clinicopathological characteristics of NSCLC was analyzed. Survival analysis was performed in combination with the follow-up data,and its prognostic significance was verified in the Kaplan-Meier Plotter database. Gene ontology( GO) and the Kyoto Encyclopedia of genes and genomes( KEGG),Panther,Reactome and Wiki pathways of SORBS1 were analyzed for gene set enrichment( GESA) using Linked Omics database. Results The SORBS1 level in NSCLC tissues was 0. 668 ± 0. 036,lower than1. 712±0. 053 in adjacent tissues( P<0. 05). Hierarchical analysis showed that the SORBS1 level was related with TNM stage,tumor size and differentiation( P<0. 05),but not with sex,age,smoking history,lymph node metastasis and pathological type( P>0. 05).Univariate analysis showed that TNM stage,tumor size,differentiation degree and tissue SORBS1 level were related to OS of NSCLC patients. Among them,the median OS of high-level patients was 57. 0 months,better than 35. 0 months of low-level patients with statistical significance( HR = 3. 033,95% CI: 1. 632-5. 637,P<0. 001). Further multivariate analysis found that tissue SORBS1 level was a risk factor for OS( HR = 2. 745,95% CI: 1. 547-5. 162,P = 0. 024). Results of GO analysis showed that the biological process of SORBS1 was mainly enriched in the regulation of cell-cell adhesion( GO: 0098742),the changes of molecular function were mainly concentrated in the structural components of extracellular matrix( GO: 0005201),and the changes of cellular components were mainly concentrated in the extracellular matrix( GO: 0031012). KEGG,Panther,Reactome and Wiki pathway analysis showed that SORBS1was enriched in cell adhesion molecule( hsa04514),chemokine and cytokine signaling pathway mediated inflammatory response( p00031),extracellular matrix tissue( R-HSA-1474244) and endochondral ossification( WP474) related pathways. Conclusion SORBS1 is low expressed in NSCLC tissues and is related to poor prognosis and malignant progression indicators. Moreover,this gene is closely related to the expression of extracellular matrix related genes and the regulation of related signaling pathways. It is expected to become a potential target for the prevention and treatment of NCSLC.更多还原