PI3K/AKT信号通路相关蛋白表达与食管癌淋巴结转移的关系
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摘要
目的探讨磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(PKB,也称AKT)信号通路相关蛋白在食管癌组织中的表达情况,并分析其与食管癌淋巴结转移和淋巴管生成的关系。方法选取120例食管癌患者,收集经组织病理学检查证实的食管癌组织和癌旁正常黏膜组织。采用免疫组织化学法检测PI3K和AKT蛋白在食管癌组织及其相应癌旁正常黏膜组织中的表达情况;采用D2-40蛋白标记淋巴管,并采用免疫组织化学法检测微淋巴管密度(LMVD),分析PI3K、AKT蛋白的表达与食管癌患者临床特征及微淋巴管密度(LMVD)的关系。结果食管癌组织中PI3K和AKT蛋白的阳性表达率分别为85.0%和86.7%,均明显高于癌旁食管正常黏膜组织的4.2%和5.8%,差异均有统计学意义(P﹤0.01)。不同性别、组织分化程度食管癌患者食管癌组织中PI3K、AKT蛋白的阳性表达率比较,差异均无统计学意义(P﹥0.05)。有淋巴结转移、TNM分期为Ⅲ+Ⅳ期的食管癌患者食管癌组织中PI3K、AKT蛋白的阳性表达率均高于无淋巴结转移、TNM分期为Ⅰ+Ⅱ期的食管癌患者,差异均有统计学意义(P﹤0.05)。PI3K蛋白阳性表达食管癌组织中LMVD的数量为(13.92±3.02),明显高于PI3K蛋白阴性表达食管癌组织的(6.54±1.05),差异有统计学意义(P﹤0.01);AKT蛋白阳性表达食管癌组织中LMVD的数量为(13.84±3.08),明显高于AKT蛋白阴性表达食管癌组织的(6.14±0.89),差异有统计学意义(P﹤0.01)。结论 PI3K/AKT信号通路相关蛋白在食管癌组织中的表达水平较高,且能够促进微淋巴管的生成和淋巴结转移,其表达情况与患者的临床特征也具有一定的关系。阻断该通路可作为治疗和预防食管癌及淋巴结转移的新的研究方向。
Objective To investigate the expression of PI3 K/AKT signaling pathway-related proteins in esophageal cancer tissues and the association with lymph node metastasis and lymphangiogenesis. Method A total of 120 cases of esophageal cancer were included in the study, from which the pathologically confirmed esophageal cancer tissues and adjacent normal mucosal tissues were collected. Immunohistochemistry was used to detect the expression of PI3 K and AKT proteins in esophageal cancer tissues and adjacent normal mucosal tissues; lymphatic vessels were stained using D2-40 protein markers, and then were detected immunohistochemically for lymphatic microvessel density(LMVD), the relationship among PI3 K and AKT protein expression and the clinical features of esophageal cancer patients and the LMVD was investigated. Result The positive expression rates of PI3 K and AKT in esophageal cancer tissues were 85.0% and86.7%, which were significantly higher than that in the normal mucosa of the esophagus at 4.2% and 5.8%, respectively,with statistically significant differences observed(P<0.01). There was no significant difference regarding the positive expression of PI3 K and AKT in patients of different gender and degree of differentiation(P>0.05). Lymph node metastasis and TNM stage III+IV were associated with significantly higher positive expression of PI3 K and AKT protein compared with absence of lymph node metastasis and TNM stage I+II, demonstrating statistically significant differences(P<0.05).The number of LMVD in the esophageal cancer tissues with positive PI3 K expression was(13.92±3.02), which was significantly higher than that in the esophageal cancer tissues with negative PI3 K expression at(6.54±1.05), and the difference was statistically significant(P<0.01). The number of LMVD in esophageal cancer tissues with positive AKT expression was(13.84±3.08), and was significantly higher than that in esophageal cancer tissues with negative AKT expression at(6.14±0.89), and the difference was statistically significant(P<0.01). Conclusion The expression of PI3 K/AKT signaling pathway-related proteins is relatively high in esophageal cancer tissues, and can promote the formation of microlymphatic vessels and lymph node metastasis, the expression is associated with patients' clinical manifestations, blocking the pathway may be a new direction for the treatment and prevention of esophageal cancer and lymph node metastasis.
Objective To investigate the expression of PI3 K/AKT signaling pathway-related proteins in esophageal cancer tissues and the association with lymph node metastasis and lymphangiogenesis. Method A total of 120 cases of esophageal cancer were included in the study, from which the pathologically confirmed esophageal cancer tissues and adjacent normal mucosal tissues were collected. Immunohistochemistry was used to detect the expression of PI3 K and AKT proteins in esophageal cancer tissues and adjacent normal mucosal tissues; lymphatic vessels were stained using D2-40 protein markers, and then were detected immunohistochemically for lymphatic microvessel density(LMVD), the relationship among PI3 K and AKT protein expression and the clinical features of esophageal cancer patients and the LMVD was investigated. Result The positive expression rates of PI3 K and AKT in esophageal cancer tissues were 85.0% and86.7%, which were significantly higher than that in the normal mucosa of the esophagus at 4.2% and 5.8%, respectively,with statistically significant differences observed(P<0.01). There was no significant difference regarding the positive expression of PI3 K and AKT in patients of different gender and degree of differentiation(P>0.05). Lymph node metastasis and TNM stage III+IV were associated with significantly higher positive expression of PI3 K and AKT protein compared with absence of lymph node metastasis and TNM stage I+II, demonstrating statistically significant differences(P<0.05).The number of LMVD in the esophageal cancer tissues with positive PI3 K expression was(13.92±3.02), which was significantly higher than that in the esophageal cancer tissues with negative PI3 K expression at(6.54±1.05), and the difference was statistically significant(P<0.01). The number of LMVD in esophageal cancer tissues with positive AKT expression was(13.84±3.08), and was significantly higher than that in esophageal cancer tissues with negative AKT expression at(6.14±0.89), and the difference was statistically significant(P<0.01). Conclusion The expression of PI3 K/AKT signaling pathway-related proteins is relatively high in esophageal cancer tissues, and can promote the formation of microlymphatic vessels and lymph node metastasis, the expression is associated with patients' clinical manifestations, blocking the pathway may be a new direction for the treatment and prevention of esophageal cancer and lymph node metastasis.
引文
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[11] Yamamoto M, Tamakawa S, Yoshie M, et al. Neoplastic hepatocyte growth associated with cyclin D1 redistribution from the cytoplasm to the nucleus in mouse hepatocarcinogenesis[J]. Mol Carcinog, 2006, 45(12):901-913.
[12]费洪荣,王凤泽. P13K/Akt信号通路的调控与肿瘤血管生成[J].生命的化学, 2010, 31(1):38-41.
[13] Li H, Gao Q, Guo L, et al. The PTEN/PI3K/Akt pathway regulates stem-like cells in primary esophageal carcinoma cells[J]. Cancer Biol Ther, 2011, 11(11):950-958.
[2] Mayer IA, Arteaga CL. The PI3K/AKT pathway as a target for cancer treatment[J]. Annu Rev Med, 2016, 67:11-28.
[3] Danielsen SA, Eide PW, Nesbakken A, et al. Portrait of the PI3K/AKT pathway in colorectal cancer[J]. Biochim Biophys Acta, 2015, 1855(1):104-121.
[4]董勤,李良,苏秀兰.血管内皮生长因子C与血管内皮生长因子D在胃癌组织中的表达及其与淋巴管密度和淋巴结转移的关系[J].中国医师进修杂志, 2013, 36(11):21-24.
[5]杨龙海,叶波,魏星,等.最新国际肺癌TNM分期标准(第8版)修订稿解读[J].中国医刊, 2016, 51(9):22-25.
[6]廖书杰,袁兵,胡晓继,等. PI3K/AKT/p-AKT在宫颈癌组织中的表达及其与Ki67关系的研究[J].肿瘤, 2008, 28(4):317-321.
[7]许振,刘志强,郭庆枝,等.宫颈癌组织AKT和P-AKT表达与LMVD相关性及其对新辅助化疗效果预测意义[J].中华肿瘤防治杂志, 2017, 24(13):906-911.
[8]赵东霞,卢安,王丽芳.食管癌组织HMGB1蛋白表达意义Meta分析[J].中华肿瘤防治杂志, 2018, 25(6):442-448.
[9] Polivka J Jr, Janku F. Molecular targets for cancer therapy in the PI3K/AKT/mTOR pathway[J]. Pharmacol Ther,2014, 142(2):164-175.
[10] Dong Y, Liang G, Yuan B, et al. MALAT1 promotes the proliferation and metastasis of osteosarcoma cells by activating the PI3K/Akt pathway[J]. Tumour Biol, 2015, 36(3):1477-1486.
[11] Yamamoto M, Tamakawa S, Yoshie M, et al. Neoplastic hepatocyte growth associated with cyclin D1 redistribution from the cytoplasm to the nucleus in mouse hepatocarcinogenesis[J]. Mol Carcinog, 2006, 45(12):901-913.
[12]费洪荣,王凤泽. P13K/Akt信号通路的调控与肿瘤血管生成[J].生命的化学, 2010, 31(1):38-41.
[13] Li H, Gao Q, Guo L, et al. The PTEN/PI3K/Akt pathway regulates stem-like cells in primary esophageal carcinoma cells[J]. Cancer Biol Ther, 2011, 11(11):950-958.
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