PI3K/Akt信号通路相关蛋白在胆管癌中的表达及其临床意义(1)
【摘要】 目的：探讨PI3K/Akt信号通路相关蛋白PI3K、Akt、PTEN在胆管癌(cholangiocarcinoma，CCA)中的表达及其临床意义。方法：收集2010年1月-2017年1月本院47例CCA患者的癌组织及对应癌旁组织标本，另选择同期14例正常胆管组织标本。比较CCA、癌旁组织及正常胆管组织中PI3K、Akt与PTEN蛋白的阳性表达率，并分析PI3K、Akt与PTEN蛋白在CCA组织中阳性表达的相关因素及相关性。结果：CCA组织中PI3K与Akt的阳性表达率均高于癌旁组织和正常胆管组织(P<0.05);CCA組织中PTEN阳性表达率均低于癌旁组织和正常胆管组织(P<0.05);CCA组织、癌旁组织及正常胆管组织的PI3K、Akt及PTEN阳性表达率比较，差异均有统计学意义(P<0.05)。有无神经侵犯、浸润深度、淋巴结转移情况及TNM分期是PI3K、Akt及PTEN蛋白在CCA组织中阳性表达的相关因素(P<0.05)。PI3K、Akt与PTEN在CCA组织中的表达呈负相关(r=-0.635、-0.506，P<0.001)，而PI3K与Akt在CCA组织中的表达呈正相关(r=0.332，P=0.023)。结论：PI3K/Akt信号传导通路在CCA组织中过度表达，可能参与了CCA的发生与发展，可作为生物学行为的评估指标，PI3K/Akt信号通路可望成为CCA临床干预的分子靶点。
【关键词】 胆管癌 PI3K/Akt信号通路 PTEN
[Abstract] Objective： To investigate the expression and clinical significance of protein PI3K， Akt and PTEN which correlated with PI3K/Akt signaling pathway in cholangiocarcinoma (CCA). Method： Cancer tissues and corresponding paracancer tissue specimens of 47 CCA patients were collected from our hospital from January 2010 to January 2017. Another 14 normal bile duct specimens were selected. The positive expression rates of PI3K， Akt and PTEN proteins in CCA， paracancer and normal bile duct tissues were compared， and the relevant factors and correlations of PI3K， Akt and PTEN proteins expressions in CCA tissues were analyzed. Result： The positive expression rates of PI3K and Akt in CCA tissues were higher than those in paracancer and normal bile duct tissues (P<0.05). The positive expression rate of PTEN in CCA tissues was lower than that in paracancer and normal bile duct tissues (P<0.05). There were significant differences in the positive expression rates of PI3K， Akt and PTEN in CCA， paracancer and normal bile duct tissues (P<0.05). The presence of nerve invasion， depth of infiltration， lymph node metastasis and TNM stage were the relevant factors for the positive expression of PI3K， Akt and PTEN in CCA tissues (P<0.05). PI3K and Akt were negatively correlated with the expression of PTEN in CCA tissues (r=-0.635， -0.506， P<0.001)， while PI3K was positively correlated with the expression of Akt in CCA tissues (r=0.332， P=0.023). Conclusion： The PI3K/Akt signaling pathway is overexpressed in CCA tissues， which may be involved in the occurrence and development of CCA， and can be used as an evaluation indicator of biological behavior， PI3K/Akt signaling pathway is expected to become a molecular target for clinical intervention of CCA.
近年来，胆管癌(cholangiocarcinoma，CCA)的发病率逐年升高，因极具侵袭转移特性，且发病隐匿，导致大多数患者确诊即为晚期，尽管根治性手术切除对部分胆管癌患者预后有所获益，但5年生存率仍不高，中位生存时间仅1～2年，预后极差，因此一直是临床上的难治性疾病之一[1-2]。在人类肿瘤谱中均发现有活动异常的信号通路，推测其可能参与肿瘤发生、发展。研究发现磷脂酰肌醇3-激酶/蛋白激酶B(phosphatidylinositol 3-kinase/protein kinase B， PI3K/Akt)信号转导通路在多种恶性肿瘤中存在异常失调现象，此通路中相关成分突变可引起通路功能异常，不仅参与癌细胞增殖分化和凋亡，还与癌细胞的侵袭转移、促肿瘤新生血管生成以及拮抗放化疗等密切相关[3-4]。PI3K作为催化磷脂酰肌醇物质的特异性激酶，通过活化Akt参与细胞增殖、分化及凋亡，Akt是PI3K下游靶蛋白，可启动下游底物调控细胞周期、抑制凋亡及促血管生成，而负性调控因子PTEN功能丢失可激活PI3K/Akt信号通路，参与肿瘤发生发展。本研究对PI3K、Akt及PTEN在CCA中的表达情况进行分析，旨在探讨其在CCA发生发展中的作用及其与CCA生物学行为的关系，从而为CCA的预防及治疗提供新思路，现报道如下。, 百拇医药(黄利勇 吴芳华 郑志刚)
【关键词】 胆管癌 PI3K/Akt信号通路 PTEN
[Abstract] Objective： To investigate the expression and clinical significance of protein PI3K， Akt and PTEN which correlated with PI3K/Akt signaling pathway in cholangiocarcinoma (CCA). Method： Cancer tissues and corresponding paracancer tissue specimens of 47 CCA patients were collected from our hospital from January 2010 to January 2017. Another 14 normal bile duct specimens were selected. The positive expression rates of PI3K， Akt and PTEN proteins in CCA， paracancer and normal bile duct tissues were compared， and the relevant factors and correlations of PI3K， Akt and PTEN proteins expressions in CCA tissues were analyzed. Result： The positive expression rates of PI3K and Akt in CCA tissues were higher than those in paracancer and normal bile duct tissues (P<0.05). The positive expression rate of PTEN in CCA tissues was lower than that in paracancer and normal bile duct tissues (P<0.05). There were significant differences in the positive expression rates of PI3K， Akt and PTEN in CCA， paracancer and normal bile duct tissues (P<0.05). The presence of nerve invasion， depth of infiltration， lymph node metastasis and TNM stage were the relevant factors for the positive expression of PI3K， Akt and PTEN in CCA tissues (P<0.05). PI3K and Akt were negatively correlated with the expression of PTEN in CCA tissues (r=-0.635， -0.506， P<0.001)， while PI3K was positively correlated with the expression of Akt in CCA tissues (r=0.332， P=0.023). Conclusion： The PI3K/Akt signaling pathway is overexpressed in CCA tissues， which may be involved in the occurrence and development of CCA， and can be used as an evaluation indicator of biological behavior， PI3K/Akt signaling pathway is expected to become a molecular target for clinical intervention of CCA.
近年来，胆管癌(cholangiocarcinoma，CCA)的发病率逐年升高，因极具侵袭转移特性，且发病隐匿，导致大多数患者确诊即为晚期，尽管根治性手术切除对部分胆管癌患者预后有所获益，但5年生存率仍不高，中位生存时间仅1～2年，预后极差，因此一直是临床上的难治性疾病之一[1-2]。在人类肿瘤谱中均发现有活动异常的信号通路，推测其可能参与肿瘤发生、发展。研究发现磷脂酰肌醇3-激酶/蛋白激酶B(phosphatidylinositol 3-kinase/protein kinase B， PI3K/Akt)信号转导通路在多种恶性肿瘤中存在异常失调现象，此通路中相关成分突变可引起通路功能异常，不仅参与癌细胞增殖分化和凋亡，还与癌细胞的侵袭转移、促肿瘤新生血管生成以及拮抗放化疗等密切相关[3-4]。PI3K作为催化磷脂酰肌醇物质的特异性激酶，通过活化Akt参与细胞增殖、分化及凋亡，Akt是PI3K下游靶蛋白，可启动下游底物调控细胞周期、抑制凋亡及促血管生成，而负性调控因子PTEN功能丢失可激活PI3K/Akt信号通路，参与肿瘤发生发展。本研究对PI3K、Akt及PTEN在CCA中的表达情况进行分析，旨在探讨其在CCA发生发展中的作用及其与CCA生物学行为的关系，从而为CCA的预防及治疗提供新思路，现报道如下。, 百拇医药(黄利勇 吴芳华 郑志刚)
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