目的 探究自噬相关基因2B(ATG2B)、转化生长因子β受体1(TGFBR1)在非小细胞肺癌(NSCLC)组织中的表达及二者与NSCLC患者预后的关系.方法 回顾性选取2018年10月至2019年10月中山大学附属第八医院收治的100例NSCLC患者术中切除的NSCLC组织及癌旁组织作为标本,收集并记录NSCLC患者性别、肿瘤直径、分化程度、病理分型、TNM分期、淋巴结转移等临床资料;免疫组织化学检测癌组织及癌旁组织中ATG2B、TGFBR1表达;Kaplan-Meier法分析NSCLC组织中ATG2B、TGFBR1表达与NSCLC患者预后的关系;多因素Cox回归分析NSCLC患者预后的影响因素.结果 NSCLC组织中ATG2B、TGFBR1阳性率分别为74.00％、68.00％,均较癌旁组织(16.00％、12.00％)明显增高,差异均有统计学意义(P＜0.05).低分化、TNM分期Ⅲ期、有淋巴结转移及器官转移的NSCLC患者ATG2B、TGFBR1阳性表达比例高于中高分化、TNM分期Ⅰ+Ⅱ期、无淋巴结转移及器官转移的NSCLC患者,差异均有统计学意义(P＜0.05).NSCLC组织ATG2B阴性表达患者3年生存率为65.38％,高于ATG2B阳性表达患者(31.08％)(Log Rank=11.808,P＜0.05),NSCLC组织TGFBR1阳性表达患者3年生存率为26.47％,低于TGFBR1阴性表达患者(68.75％)(Log Rank=21.768,P＜0.05).生存组低分化、TNM为Ⅲ期、淋巴结转移及器官转移的比例明显低于死亡组,差异均有统计学意义(P＜0.05).Cox回归分析显示TNM分期、淋巴结转移与ATG2B、TGFBR1表达水平均是NSCLC不良预后的危险因素(P＜0.05).结论 ATG2B、TGFBR1在NSCLC患者癌组织中高表达,且二者均是NSCLC患者预后不良的危险因素.

目的 探讨木酮糖激酶rs17118多态性与冠心病发病风险的关联性.方法 纳入2016年6月至2018年2月在深圳市中山大学附属第八医院诊治的、资料完整并成功完成基因分型的患者.按照1:1的比例,选择年龄、性别匹配的冠心病患者(病例组)和健康体检者(对照组)各597例,采用Taqman探针荧光定量PCR技术检测rs17118 C/A基因型分布情况,应用多因素logistic回归分析各位点多态性与冠心病的关联性.结果 病例组CA基因型(44.6％比38.5％,χ2=4.536,P=0.038)以及CA+AA基因型(51.6％比45.7％,χ2=4.008,P=0.045)分布频率均高于对照组.多变量logistic回归分析显示,校正传统危险因素后,CA基因型携带者冠心病发病风险是CC基因型携带者的1.41倍(95％CI:1.03～1.94,P=0.034).病例组中,AA基因型携带者低密度脂蛋白胆固醇[(2.31±0.82)mmol/L]和总胆固醇[(3.93±1.22)mmol/L]水平明显低于CC基因型[(2.61±0.86)mmol/L、(4.40±1.19)mmol/L,P=0.050、0.035]和CA基因型[(2.68±0.82)mmol/L、(4.49±1.22)mmol/L,P=0.016、0.012],CA+AA基因型携带者高密度脂蛋白胆固醇水平也明显低于CC基因型携带者[(1.05±0.26)mmol/L比(1.10±0.31)mmol/L,P=0.035].结论 木酮糖激酶基因可能通过调整脂质代谢,影响冠状动脉粥样硬化的形成和发展,进而改变个体的疾病遗传易感性,rs17118多态性与中国汉族人群冠心病发病风险有关.

Background and purpose: miRNA is supposed to be involved in the occurrence and progression of tumors. However, studies are still inadequate. This study aimed to investigate whether miR-933 can inhibit cell proliferation, migration and invasion and induce apoptosis of lung cancer cell lines A549 and H460 by regulating Kruppel-like zinc finger transcription factor 6 (KLF6). Methods: Expression of miR-933 in lung cancer cell lines (A549, H460) and bronchial epithelial cells (BEAS-2B) was detected using real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR). Lung cancer cells were transfected with miR-933 mimic and mimic NC, respectively. RTFQ-PCR and Western blot were performed to detect expression of KLF6 in A549 and H460. Cell proliferation was detected by cell counting kit-8 (CCK-8) assay and EdU assay, migration and invasion were detected by transwell assay, and apoptosis was detected by Annexin Ⅴ-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining. Results: Results of RTFQ-PCR showed that the expression of KLF6 in lung cancer cell lines transfected with miR-933 mimic was obviously upregulated (P<0.05). Western blot assay displayed that expression of KLF6 protein increased in A549 and H460 transfected with miR-933 mimic separately (P<0.05). Compared with negative control, the abilities of cell proliferation, migration and invasion in both A549 and H460 cells were significantly inhibited by overexpression of miR-933 (P<0.05). Annexin Ⅴ-FITC/PI staining results showed that apoptotic rates were 48.3%±1.0% and 6.1%±0.2% respectively in A549 and H460 cells after transfection of miR-933 mimic, compared with negative control (37.6%±0.9%, 2.7%±0.01% (P<0.001). Conclusion: By regulating KLF6, miR-933 induces apoptosis, inhibits cell proliferation, reduces abilities of migration and invasion of lung cancer cells and delays the occurrence and development of lung cancer.

目的 探讨miR-671-5 p调控非小细胞肺癌细胞系增殖、迁移和侵袭的作用机制.方法 采用实时荧光定量PCR(RT-qPCR)法检测人正常肺上皮细胞系(BEAS-2B)和非小细胞肺癌细胞系(A549和H460)中miR-671-5p及其靶基因Kruppel样锌指转录因子6(KLF6)mRNA表达量.miR-671-5p mimic转染A549和H460细胞,设置阴性对照序列,蛋白质印迹法检测KLF6蛋白表达,细胞计数试剂盒(CCK-8)法、EdU法和Transwell小室法分别检测非小细胞肺癌细胞的增殖、迁移和侵袭能力.结果 与BEAS-2B细胞比较,miR-671-5p在A549和H460细胞中高表达,表达量分别为1.646±0.026和1.638±0.027,差异有统计学意义,F=153.900,P<0.001;KLF6在A549和H460中的mRNA表达量降低,分别为0.233±0.005和0.382±0.003,差异有统计学意义,F=2077.000,P<0.001;转染miR-671-5p mimic后,A549和H460细胞的增殖、迁移和侵袭能力增强(均P<0.05),KLF6的mRNA和蛋白表达水平受到抑制,其中A549和H460细胞KLF6蛋白水平分别下调至0.252±0.011(t=23.970,P<0.001)和0.290±0.017(t=16.140,P<0.001).结论 miR-671-5p可能通过调控KLF6基因促进非小细胞肺癌细胞系的增殖、迁移及侵袭,进而影响非小细胞肺癌的发生和发展.