神经元正五聚蛋白2在结直肠癌组织的表达及对其侵袭迁移的调控

Expression of neuronal pentraxin 2 in colorectal cancer and its regulatory effect on invasion and migration

目的探讨神经元正五聚蛋白2(NPTX2)在结直肠癌组织的表达以及对结直肠癌细胞侵袭和迁移的调控.方法应用免疫组织化学(IHC)检测101例结直肠癌及配对癌旁组织石蜡包埋标本NPTX2蛋白表达水平,观察其与患者临床病理学参数的关系;再以实时定量反转录聚合酶链反应(RT-qPCR)和蛋白质印迹法(Western blot)检测18对新鲜配对结直肠癌和癌旁组织NPTX2蛋白和mRNA表达水平,最后利用小干扰RNA(siRNA)检测NPTX2沉默对结直肠癌细胞侵袭和迁移的影响及其机制.结果NPTX2在101例结直肠癌中表达明显高于配对的癌旁正常组织(Z=-6.083,P<0.01).NPTX2高表达与结直肠癌患者肿瘤大小(x^2=7.324,P<0.01)、T分期(x^2=5.811,P<0.05)及TNM分期(x^2=4.791,P<0.05)呈明显正相关.NPTX2高表达结直肠癌患者预后不良(P<0.01).NPTX2在18例结直肠癌中mRNA和蛋白表达均明显高于配对的癌旁组织(t=2.612、2.533,P<0.05).且NPTX2沉默抑制SW480肠癌细胞侵袭和迁移力,并同时伴随E-钙黏蛋白表达上调,及N-钙黏蛋白和Snail表达下调.结论NPTX2在结直肠癌中高表达与患者肿瘤大小、T分期、TNM分期及不良预后密切相关,NPTX2可能通过调控上皮细胞间质转化促进结直肠癌侵袭和迁移.

Objective To study the clinicopathological significance and malignant behavior of human colorectal cancer(CRC)with the expression of neuronal pentraxin 2(NPTX2).Methods NPTX2 expression in 101 CRC and paired adjacent normal tissues and its clinicopathological significance were detected by immunohistochemistry(IHC).Real-time quantitative reverse transcriptase-polymerase chain reaction(RT-qPCR)and Western blotting were used to examine NPTX2 protein and mRNA levels in 18 paired CRC and adjuvant normal tissues.Finally,small interfering RNA(siRNA)was used to detect the effect of NPTX2 silencing on CRC cell invasion and migration and its possible mechanism.Results NPTX2 expression in CRC tissues was significantly higher than that in non-cancerous tissues(Z=-6.083,P<0.01).NPTX2 overexpression was positively associated with tumor size(χ^2=7.324,P<0.01),T stage(χ^2=5.811,P<0.05)and TNM stage(χ^2=4.791,P<0.05).Moreover,patients with NPTX2 high expression had a worse prognosis(P<0.01).RT-qPCR and Western blotting showed that NPTX2 mRNA and protein levels in 18 CRC tissues were significantly higher than those in paired normal tissues(t=2.612,P<0.05;t=2.533,P<0.05).Meanwhile,NPTX2 silence inhibited cell invasion and migration in SW480 cell lines,along with the increase of E-cadherin and decrease of N-cadherin and snaill.Conclusion NPTX2 overexpression promotes the development and progression of human colorectal cancer.