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驱动蛋白超家族18A在胃癌组织中的表达及其与患者预后的关系

Expression of KIF18A in gastric cancer and its association with prognosis

摘要目的:探讨驱动蛋白超家族(KIF)中kinesin-8家族中的KIF18A基因蛋白在胃癌组织中的表达及其与患者预后的关系。方法20例胃癌患者的新鲜胃癌组织及相应癌旁正常组织(距离肿瘤>5 cm)样本来自安徽医科大学第一附属医院普通外科2015年3—7月期间接受手术治疗者,运用实时荧光定量PCR方法,检测胃癌及相应癌旁组织中KIF18A的 mRNA水平;另收集2006年11月至2008年5月期间在安徽医科大学第一附属医院普通外科治疗的129例胃癌患者的临床及随访资料,并将标本数据库中保存的该组患者石蜡包埋胃癌手术标本和23例随机挑选的正常组织(非癌旁胃组织)制成组织芯片,通过免疫组织化学(免疫组化)方法进行染色,并由病理医师确认结果后,检测KIF18A蛋白在组织芯片中的表达情况,采用χ2检验或Fisher精确概率法分析其表达与胃癌患者临床病理特征及预后的关系;采用Kaplan-Meier法绘制生存曲线,并采用Log-rank检验进行生存比较,Cox比例风险模型进行预后危险因素分析。结果 KIF18A mRNA在20例胃癌新鲜样本中的表达水平中,有16例显示胃癌组织低于癌旁组织。组织芯片中,胃癌组织KIF18A蛋白表达阳性率亦明显低于正常胃组织[45.0%(58/129)比69.6%(16/23),P=0.041]。KIF18A蛋白表达与胃癌浸润深度(P =0.008)和TNM分期(P =0.032)有关。129例胃癌患者中位总生存时间为44.0(95% CI:39.8~49.2)月,其中KIF18A阳性与阴性表达者3年生存率分别为67.2%和36.6%,差异有统计学差异(P=0.020)。 Cox回归分析显示,KIF18A表达是胃癌患者预后的独立保护因素(HR=0.570,95%CI:0.335~0.970)。结论 KIF18A在胃癌组织中表达下调,提示其可能在胃癌的发生过程中具有重要作用;KIF18A低表达的胃癌患者预后较差,可能是一个潜在的预后标志物。

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abstractsObjective To explore the expression of KIF18A gene protein in gastric cancer tissues and its association with the prognosis of patients. Methods Twenty fresh paired gastric cancer specimens and adjacent normal mucosa (at least 5 cm from the edge of tumor) from 20 gastric cancer patients undergoing operation in Department of General Surgery at the First Affiliated Hosptial of Anhui Medical University between March 2015 and July 2015 were collected. Real-time PCR was used to examine KIF18A mRNA expression in above specimens. Meanwhile, paraffin embedded cancer tissue samples from 129 gastric cancer patients undergoing operation and 23 samples of randomly selected normal gastric tissue (adjacent non-cancer tissue) were collected to establish the microarray. Immunohistochemistry method was applied to detect the KIF18A protein expression in the microarray after confirmation by pathologists. Association of KIF18A expression with clinicopathological features in gastric cancer patients was evaluated. Cox proportional hazard model was used to identify prognostic risk factors. Results Among 20 fresh paired gastric cancer specimens, mRNA expression of KIF18A in 16 specimens was obviously lower than that in adjacent normal tissues. The positive rate of KIF18A protein expression in gastric cancer tissues was significantly lower than that in normal gastric tissues in microarray [45.0%(58/129) vs. 69.6%(16/23), P = 0.041]. KIF18A protein expression was significantly associated with invasion depth (P = 0.008) and TNM staging (P = 0.032). The median overall survival of all the 129 patients was 44.0 (95% CI: 39.78 - 49.24) months. The three-year survival rates of patients with high and low KIF18A expression were 67.2% and 36.6% respectively (P = 0.020). Cox regression analysis showed that KIF18A expression was an independent protective factor of the prognosis of gastric cancer patients (HR=0.570, 95%CI:0.335 to 0.970). Conclusions KIF18A expression is down-regulated in gastric cancer tissue, which may play a critical role in gastric cancer carcinogenesis. Lower expression of KIF18A is associated with poor prognosis of gastric cancer patients. KIF18A may be a potential prognostic marker of gastric cancer.

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中华胃肠外科杂志

中华胃肠外科杂志

2016年19卷5期

585-589页

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