Depression and oxidative damage in TNM stage Ⅲ patients with poorly differentiated gastric adenocarcinoma

Objective To investigate the association between psychological stress and oxidative damage in TNM stage Ⅲ patients with poorly differentiated gastric adenocarcinoma (GA). Methods One hundred and six patients with newly diagnosed poorly differentiated GA were assessed using the Hamilton Depression Rating Scale (HAMD), Zung Self-rating Depression Scale (SDS), Zung Self-rating Anxiety Scale (SAS), Symptom Checklist 90 (SCL-90), activities of daily living (ADL) and other multiple-item questionnaires. Oxidative-stress-related parameters in serum and the expression of DNA repair genes were monitored during a pretreatment period. Results The patients were divided into depression and nondepression groups (Groups A and B, respectively) based on a HAMD score cutoff of 20. The mean SDS, SAS, SCL-90, ADL and passive coping scores were higher in Group A, whereas social support and quality of life were lower. Serum total antioxidant capacity, catalase, superoxide dismutase concentrations and anti-superoxide anion capacity (A-ASC) were significantly decreased in Group A, whereas serum malondialdehyde (MDA) and 8-hydroxy-deoxyguanosine (8-OHdG) levels were significantly increased. Pearson correlation analysis revealed that depression was positively correlated with MDA, SAS, SCL-90 and ADL, but negatively correlated with A-ASC. Furthermore, real-time PCR revealed that the expression levels of hOGG1 and APEX1 were increased in Group A. Conclusion Psychological stress might be related to impaired antioxidant system in patients with GA, and it presents the first evidence of the involvement of oxidative DNA damage in the pathogenesis of depression.

基于芯片技术探讨结直肠癌中沉默DNA结合蛋白A的基因表达谱分析

目的基于基因芯片技术探讨短发夹RNA沉默人结直肠癌细胞DNA结合蛋白A(dbpA)表达后利用基因本体(GO)和京都基因与基因组百科全书(KEGG)分析发现与dbpA相关的结直肠癌发生、发展的信号通路。方法选取结直肠癌SW620细胞中表达差异的基因进行深度检测和分析,采用基因芯片技术挖掘差异基因,并运用定量反转录聚合酶链反应(RT-PCR)对芯片结果进行验证,综合分析工具进行GO功能富集分析及KEGG信号通路分析。结果dbpA敲低后基因芯片检测差异表达基因有578条,其中181个基因上调,397个基因下调,显著上调基因有CFL2、C12orf39、EREG、SESN2、CXCL3、CXCL1、VLDVR、DDIT4、INHBE等60个基因,显著下调基因在PRDM10、PCDH19、SRSF8、FGFBP1、TFF2、MTDH、TCF7、EHHADH、WDR77、CEACAM6等60个基因。dbpA敲除后SW620细胞中与肿瘤形成有关的通路主要与“生物过程”有关,包括丝裂原活化蛋白激酶信号通路、癌症途径、NOD样受体信号通路、趋化因子信号通路、粘着斑、基底细胞癌、Wnt信号通路等。基因网络图分析显示有10个基因表达水平下降(FASLG、PDGFA、FGF18、MAP3K7、FGF3、CSDA、NF1、RAP1A、HSPA1A、LAMTOR3等),4个基因表达水平上升(DUSP5、PRAS2、CDC42、DUSP2等),dbpA与MAPK信号通路相关性最大。选择KMAPK信号通路中的5个相关基因即RAPIA、TAK1(MAP3K7)、DUSP5、CDC42、ZAK进行Western blot验证表明,DUSP5表达水平明显上调(P<0.05),RAP1A、TAK1、ZAK表达水平下降,RAP1A、TAK1表达水平下降明显(P<0.05)。dbpA可能通过MAPK通路调节结直肠癌细胞的发生。结论dbpA参与调控的靶基因和信号通路可能为MAPK相关通路,还需要进一步在多细胞和动物实验中研究揭示dbpA下调通路之间的关系及CDC42在结直肠癌发展中的作用。