LPA2、KLF5在胃腺癌组织中的表达及其临床病理学意义

发布时间：2019-01-19 19:16

【摘要】：目的:研究溶血磷脂酸受体2蛋白(LPA2)、Krüppel样因子5(KLF5)在胃正常黏膜、上皮内瘤变和胃腺癌组织芯片中表达水平的差异,分析两种蛋白与胃腺癌患者临床病理特征的关系,以及在胃腺癌中两者之间的相关性,并进一步探讨溶血磷脂酸受体2蛋白(LPA2)及Krüppel样因子5(KLF5)在胃腺癌发生、发展及预后中的作用。方法:选取51例手术切除胃腺癌组织标本、21例上皮内瘤变标本及13例正常胃黏膜标本为研究对象,并制作组织芯片,采用免疫组织化学SP法检测LPA2和KLF5在胃正常黏膜、上皮内瘤变和胃腺癌组织中的表达,并分析两种蛋白与患者预后的相关性。结果:1.LPA2主要表达于细胞质和胞膜,呈棕褐色颗粒状,在胃低分化腺癌组、中分化腺癌组、高分化腺癌组、高级别上皮内瘤变组、低级别上皮内瘤变组及正常胃黏膜组中的阳性表达率分别为89.5%(17/19)、81.3%(13/16)、25.0%(4/16)、33.3%(3/9)、25.0%(3/12)和23.1%(3/13),癌组织的阳性率显著高于上皮内瘤变组织和正常胃黏膜组织,差异具有统计学意义(χ2=29.9,P0.001)。2.LPA2蛋白在高级别上皮内瘤变组织中的阳性表达率为33.3%(3/9);高分化腺癌组织中LPA2蛋白的阳性率为25.0%(4/16),两组患者LPA2蛋白的阳性率差异无统计学意义(χ2=0.20,P0.05)。3.在胃腺癌组织中,LPA2阳性表达与患者年龄、性别、肿瘤的部位、肿瘤的直径及组织学分级无关(P0.05),而与患者肿瘤的浸润深度、Lauren分型、是否侵犯脉管、区域淋巴结转移情况及临床分期有关(P0.05)。浸润浆膜层、Lauren分型弥漫型、有脉管侵犯、存在区域淋巴结转移和晚期的患者LPA2阳性率显著高于未浸润浆膜层、Lauren分型肠型、无脉管侵犯、无区域淋巴结转移和早期的患者。4.KLF5主要表达于细胞质,呈棕褐色颗粒状,在胃低分化腺癌组、中分化腺癌组、高分化腺癌组、高级别上皮内瘤变组、低级别上皮内瘤变组及正常胃黏膜组中的阳性表达率分别为78.9%(15/19)、75.0%(12/16)、75.0%(12/16)、66.7%(6/9)、58.3%(7/12)和38.5%(5/13),癌组织的阳性率高于上皮内瘤变组织和正常胃黏膜组织,阳性表达率逐渐降低,但差异无统计学意义(χ2=7.35,P0.05)。5.在胃腺癌组织中,KLF5的阳性表达与患者年龄、性别、肿瘤的部位、肿瘤的直径、组织学分级、浸润深度、Lauren分型、是否侵犯脉管、区域淋巴结转移情况及临床分期均无关,差异无统计学意义(P0.05)。6.在胃腺癌组织中,LPA2阳性组和阴性组的患者中位生存时间分别为11.02个月和23.04个月,两组比较死亡风险差别有统计学意义(HR=1.89,95%CI:1.11-3.63,P0.05)。7.在胃腺癌组织中,KLF5阳性组和阴性组的患者中位生存时间分别为10.7个月和12.1个月,两组比较死亡风险差别无统计学意义(HR=1.11,95%CI:0.53-2.363,P0.05)。8.在胃腺癌组织中,KLF5与LPA2蛋白的表达呈正相关性(γ=0.66,P0.05)。结论:1.LPA2蛋白在胃腺癌组织中高表达,其阳性表达与患者肿瘤的浸润深度、Lauren分型、是否侵犯脉管、区域淋巴结转移情况及临床分期有密切关系,提示LPA2可能参与胃腺癌的发生,并且可作为判断胃腺癌发展、转移的一个重要指标。2.LPA2蛋白在胃腺癌中阳性组患者较阴性组患者生存时间短,提示其检测可能有助于评估胃腺癌患者的预后。3.KLF5与LPA2在胃腺癌组织中的表达呈正相关,提示两者间可能存在一种相互关联的机制,从而在胃腺癌中发挥作用。
[Abstract]:Objective: To study the relationship between the expression level of lysophosphatidic acid receptor 2 protein (LPA2) and Kr-ppel-like factor 5 (KLF5) in normal gastric mucosa, intraepithelial neoplasia and gastric adenocarcinoma, and to analyze the relationship between the two proteins and the clinicopathological features of gastric adenocarcinoma. The relationship between the expression of lysophosphatidic acid receptor 2 protein (LPA2) and Kr-ppel-like factor 5 (KLF5) in the occurrence, development and prognosis of gastric adenocarcinoma was further discussed. Methods: 51 cases of gastric adenocarcinoma, 21 cases of intraepithelial neoplasia and 13 normal gastric mucosa specimens were selected as the research object, and the tissue chip was made. The expression of LPA2 and KLF5 in the normal mucosa, intraepithelial neoplasia and gastric adenocarcinoma was detected by immunohistochemical SP method. The relationship between the two proteins and the prognosis of the patients was analyzed. Results: 1. LPA2 is mainly expressed in the cytoplasm and the cell membrane, which is brown-brown, and the positive expression rates in the low-grade adenocarcinoma group, the high-grade adenocarcinoma group, the high-grade intraepithelial neoplasia group, the low-grade intraepithelial neoplasia group and the normal gastric mucosa group are 89.5% (17/ 19), 81.3% (13/ 16), 25. 0% (4/ 16), 33. 3% (3/ 9), 25. 0% (3/ 12) and 23. 1% (3/ 13), respectively. The positive rate of LPA2 in high-grade intraepithelial neoplasia was 33. 3% (3/ 9), and the positive rate of LPA2 in high-grade adenocarcinoma was 25. 0% (4/ 16). There was no significant difference in the positive rate of LPA2 protein in the two groups (Sup2 = 0.20, P0.05). In the gastric adenocarcinoma, the positive expression of LPA2 was not related to the patient's age, sex, location of the tumor, the diameter of the tumor and the histological grade (P0.05). The positive rate of LPA2 in the infiltration of the serosal layer and the Lauren type was significantly higher than that of the non-invasive serosal layer, the Lauren type intestinal type, the non-vascular invasion, the non-regional lymph node metastasis and the earlier patients. The positive rate of expression was 78.9% (15/ 19), 75. 0% (12/ 16), 75. 0% (12/ 16), 66. 7% (6/ 9), 58. 3% (7/ 12) and 38. 5% (5/ 13), respectively. The positive rate of the cancerous tissue was higher than that of the intraepithelial neoplasia and the normal gastric mucosa. The positive rate of expression was gradually decreased, but the difference was not significant (Sup2 = 7.35, P0.05). In gastric adenocarcinoma, the positive expression of KLF5 was not related to the age of the patient, the sex, the location of the tumor, the diameter of the tumor, the histological grade, the depth of infiltration, the Lauren type, the invasion of the vessel, the metastasis of the regional lymph node and the clinical stage, and the difference was not significant (P0.05). In gastric adenocarcinoma, the survival time of patients with LPA2-positive and negative groups was 11. 02 months and 23. 04 months, respectively. There was a significant difference in the risk of death between the two groups (HR = 1.89, 95% CI: 1.11-3.63, P0.05). In the gastric adenocarcinoma, the survival time of the patients in the KLF5 positive group and the negative group was 10. 7 months and 12 months, respectively. There was no statistical significance between the two groups (HR = 1.11, 95% CI: 0.53-2.363, P0.05). In gastric adenocarcinoma, the expression of KLF5 and LPA2 protein was positively correlated (P = 0.66, P0.05). Conclusion: 1. The expression of LPA2 in gastric adenocarcinoma is closely related to the depth of infiltration of tumor, the type of Lauren, the invasion of vessel, regional lymph node metastasis and clinical stage, and it is suggested that LPA2 may be involved in the development of gastric adenocarcinoma. and can be used as an important index for judging the development and metastasis of gastric adenocarcinoma. It is suggested that there may be a mechanism of interassociation between the two, so as to play a role in the gastric adenocarcinoma.
【学位授予单位】：兰州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.2

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