HER2-HER3共表达和磷酸化mTOR在胃癌患者中的阳性预后价值。
Positive prognostic value of HER2-HER3 co-expression and p-mTOR in gastric cancer patients.
作者信息
Cao Guo-Dong, Chen Ke, Chen Bo, Xiong Mao-Ming
机构信息
Anhui Medical University, Hefei, Anhui, 230022, China.
Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, China.
出版信息
BMC Cancer. 2017 Dec 12;17(1):841. doi: 10.1186/s12885-017-3851-y.
BACKGROUND
The HER2-HER3 heterodimer significantly decreases survival in breast cancer patients. However, the prognostic value of HER2-HER3 overexpression remains unknown in gastric cancer (GC).
METHODS
The expression levels of HER2, HER3, Akt, p-Akt, mTOR and p-mTOR were examined in specimens from 120 GC patients by immunohistochemistry and quantitative reverse transcription-PCR. The associations of HER proteins, PI3K/Akt/mTOR pathway-related proteins, clinicopathological features of GC, and overall survival (OS) were assessed. To comprehensively evaluate the prognostic values of pathway-related proteins, meta-analyses were conducted with STATA 11.0.
RESULTS
HER2 overexpression was significantly associated with HER3 levels (P = 0.02). HER3 was highly expressed in gastric cancer tissues. High HER2 and HER3 levels were associated with elevated p-Akt and p-mTOR amounts (P < 0.05). Furthermore, HER2-HER3 co-expression was associated with high p-Akt and p-mTOR (P < 0.05) levels. Meanwhile, p-mTOR overexpression was tightly associated with differentiation, depth of invasion, lymph node metastasis, TNM stage and OS (P < 0.05). By meta-analyses, Akt, p-Akt, and mTOR levels were unrelated to clinicopathological characters. HER3 overexpression was associated with depth of invasion (OR = 2.39, 95%CI 1.62-3.54, P < 0.001) and lymph node metastasis (OR = 2.35, 95%CI 1.34-4.11, P = 0.003). Further, p-mTOR overexpression was associated with patient age, tumor location, depth of invasion (OR = 1.63, 95%CI 1.08-2.45, P = 0.02) and TNM stage (OR = 1.73, 95%CI 1.29-2.32, P < 0.001). In addition, HER2-HER3 overexpression corresponded to gradually shortened 5-year OS (P < 0.05), and significant relationships were shown among HER3, p-mTOR overexpression, and 1-, 3-, 5-year OS (P < 0.05).
CONCLUSIONS
HER2-HER3 co-expression may potentially enhance mTOR phosphorylation. HER2-HER3 co-expression and p-mTOR are both related to the prognosis of GC patients.
背景
HER2-HER3异二聚体显著降低乳腺癌患者的生存率。然而，HER2-HER3过表达在胃癌（GC）中的预后价值仍不清楚。
方法
通过免疫组织化学和定量逆转录PCR检测120例GC患者标本中HER2、HER3、Akt、p-Akt、mTOR和p-mTOR的表达水平。评估HER蛋白、PI3K/Akt/mTOR信号通路相关蛋白、GC的临床病理特征与总生存期（OS）之间的关联。为全面评估信号通路相关蛋白的预后价值，使用STATA 11.0进行荟萃分析。
结果
HER2过表达与HER3水平显著相关（P = 0.02）。HER3在胃癌组织中高表达。HER2和HER3高表达与p-Akt和p-mTOR水平升高相关（P < 0.05）。此外，HER2-HER3共表达与高p-Akt和p-mTOR水平相关（P < 0.05）。同时，p-mTOR过表达与分化程度、浸润深度、淋巴结转移、TNM分期及OS密切相关（P < 0.05）。通过荟萃分析，Akt、p-Akt和mTOR水平与临床病理特征无关。HER3过表达与浸润深度（OR = 2.39，95%CI 1.62 - 3.54，P < 0.001）和淋巴结转移（OR = 2.35，95%CI 1.34 - 4.11，P = 0.003）相关。此外，p-mTOR过表达与患者年龄、肿瘤位置、浸润深度（OR = 1.63，95%CI 1.08 - 2.45，P = 0.02）和TNM分期（OR = 1.73，95%CI 1.29 - 2.32，P < 0.001）相关。此外，HER2-HER3过表达对应5年OS逐渐缩短（P < 0.05），并且HER3、p-mTOR过表达与1年、3年、5年OS之间存在显著相关性（P < 0.05）。
结论
HER2-HER3共表达可能会增强mTOR磷酸化。HER2-HER3共表达和p-mTOR均与GC患者的预后相关。
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