PI3K/Akt/mTOR信号通路相关蛋白在结直肠癌中的表达及与临床病理特征和预后的关系*

Expression of protein associated with PI3K/Akt/mTOR pathway and its relationship with clinical pathology and prognosis in colorectal cancer*

摘要:

目的?探究PI3K/Akt/mTOR信号通路中PTEN、p-Akt和p-mTOR在结直肠癌中的表达及与临床病理特征和预后的关系。方法?选取2016年1月—2017年12月中国人民武装警察部队海警总队医院52例结直肠癌活检标本。采用免疫组织化学SP法检测PI3K-Akt-mTOR信号通路相关蛋白在结肠癌标本及癌旁正常组织标本中的表达；Logistic回归模型分析PI3K-Akt-mTOR信号通路相关蛋白表达与临床病理特征的关系；Kaplan-Meier生存曲线分析PI3K-Akt-mTOR信号通路相关蛋白表达与预后的关系。结果?结肠癌组织中PTEN阳性率低于癌旁正常组织（P?<0.05），而p-Akt、p-mTOR阳性率均高于癌旁正常组织（P?<0.05）；淋巴结转移患者的p-Akt和p-mTOR阳性率均高于无淋巴结转移患者（P?<0.05）；肿瘤浸润达到浆膜层患者的p-Akt阳性率高于未达浆膜层患者（P?<0.05）；肿瘤低分化患者的p-Akt阳性率高于高、中分化患者（P?<0.05）。临床分期Ⅲ、Ⅳ期患者的p-Akt和p-mTOR阳性率均高于Ⅰ、Ⅱ期患者（P?<0.05）。结直肠癌患者临床分期Ⅲ、Ⅳ期[OlR=4.098（95% CI：2.337，7.134）]是p-Akt阳性表达的影响因素（P?<0.05）。PTEN阳性患者的4年生存率为59.62%，高于阴性患者的21.15%（P?<0.05）；p-Akt阴性患者4年生存率为65.38%，高于阳性患者的19.23%（P?<0.05）；p-mTOR阴性患者4年生存率为61.54%，高于阳性患者的21.15%（P?<0.05）。结论?PI3K/Akt/mTOR信号通路相关蛋白的表达与结直肠癌的发展、预后密切相关，p-Akt、p-mTOR有望成为新的结直肠癌治疗靶点和临床指标。

Abstract:

Objective To research on expression of protein associated with PI3K/Akt/mTOR pathway and its relationship with clinical pathology and prognosis in colorectal cancer.?Methods?Fifty-two cases of colorectal cancer biopsy specimens in our hospital from January 2016 to December 2017 were involved in the study. The immunohistochemistry (IHC) was applied to detect expression of protein associated with PI3K/Akt/mTOR pathway in the cancerous tissues and their adjacent normal tissues. Multiple logistic regression model was used to analyze the relationship between expression of protein associated with PI3K/Akt/mTOR pathway and clinicopathological characteristics of patients with colorectal cancer. Kaplan-Meier survival curve was used to analyze the relationship between expression of protein associated with PI3K/Akt/mTOR pathway and prognosis in patients with colorectal cancer.?Results?The positive expression rates of PTEN in colorectal cancerous tissues was lower than that in normal tissues, but p-Akt and p-mTOR were higher than those in normal tissues adjacent to cancerous tissues (P < 0.05). The positive rate of p-Akt and that of p-mTOR in patients with lymph node metastasis were higher than those in patients without lymph node metastasis (P < 0.05). The positive rate of p-Akt in patients with tumor invading the serosa was higher than that in patients with tumor not invading the serosa (P < 0.05). The positive rate of p-Akt in patients with poorly differentiated tumors was higher than that in patients with tumors of well and intermediate differentiation (P < 0.05). The positive rates of p-Akt and p-mTOR in patients with tumors of stage Ⅲ+Ⅳ were higher than those with tumors of stage Ⅰ+Ⅱ (P < 0.05). There were no statistically significant differences in the positive rates of PTEN, p-Akt, and p-mTOR among other factors (P > 0.05). The tumor stage Ⅲ+Ⅳ was the influencing factor of positive expression of p-Akt [OlR?=?4.098, (95% CI: 2.337, 7.134)] (P < 0.05). The 4-year survival rate of patients with positive expression of PTEN was 59.62%, higher than that (21.15%) of patients with negative expression of PTEN (χ2?=?15.975, P < 0.001). The 4-year survival rate of patients with negative expression of p-Akt was 65.38%, higher than that (19.23%) of patients with positive expression of p-Akt (χ2?=?22.691, P < 0.001). Furthermore, the 4-year survival rate of patients with negative expression of p-mTOR was 61.54%, higher than that (21.15%) of patients with positive expression of p-mTOR (P?< 0.05).?Conclusions?The expression of protein associated with PI3K/Akt/mTOR pathway is closely related to the development and prognosis of colorectal cancer, and p-Akt and p-mTOR are promising therapeutic targets and valuable clinical indexes for colorectal cancer.