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LPA2、KLF5在胃腺癌組織中的表達(dá)及其臨床病理學(xué)意義

發(fā)布時(shí)間:2019-01-19 19:16
【摘要】:目的:研究溶血磷脂酸受體2蛋白(LPA2)、Krüppel樣因子5(KLF5)在胃正常黏膜、上皮內(nèi)瘤變和胃腺癌組織芯片中表達(dá)水平的差異,分析兩種蛋白與胃腺癌患者臨床病理特征的關(guān)系,以及在胃腺癌中兩者之間的相關(guān)性,并進(jìn)一步探討溶血磷脂酸受體2蛋白(LPA2)及Krüppel樣因子5(KLF5)在胃腺癌發(fā)生、發(fā)展及預(yù)后中的作用。方法:選取51例手術(shù)切除胃腺癌組織標(biāo)本、21例上皮內(nèi)瘤變標(biāo)本及13例正常胃黏膜標(biāo)本為研究對(duì)象,并制作組織芯片,采用免疫組織化學(xué)SP法檢測(cè)LPA2和KLF5在胃正常黏膜、上皮內(nèi)瘤變和胃腺癌組織中的表達(dá),并分析兩種蛋白與患者預(yù)后的相關(guān)性。結(jié)果:1.LPA2主要表達(dá)于細(xì)胞質(zhì)和胞膜,呈棕褐色顆粒狀,在胃低分化腺癌組、中分化腺癌組、高分化腺癌組、高級(jí)別上皮內(nèi)瘤變組、低級(jí)別上皮內(nèi)瘤變組及正常胃黏膜組中的陽(yáng)性表達(dá)率分別為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),癌組織的陽(yáng)性率顯著高于上皮內(nèi)瘤變組織和正常胃黏膜組織,差異具有統(tǒng)計(jì)學(xué)意義(χ2=29.9,P0.001)。2.LPA2蛋白在高級(jí)別上皮內(nèi)瘤變組織中的陽(yáng)性表達(dá)率為33.3%(3/9);高分化腺癌組織中LPA2蛋白的陽(yáng)性率為25.0%(4/16),兩組患者LPA2蛋白的陽(yáng)性率差異無(wú)統(tǒng)計(jì)學(xué)意義(χ2=0.20,P0.05)。3.在胃腺癌組織中,LPA2陽(yáng)性表達(dá)與患者年齡、性別、腫瘤的部位、腫瘤的直徑及組織學(xué)分級(jí)無(wú)關(guān)(P0.05),而與患者腫瘤的浸潤(rùn)深度、Lauren分型、是否侵犯脈管、區(qū)域淋巴結(jié)轉(zhuǎn)移情況及臨床分期有關(guān)(P0.05)。浸潤(rùn)漿膜層、Lauren分型彌漫型、有脈管侵犯、存在區(qū)域淋巴結(jié)轉(zhuǎn)移和晚期的患者LPA2陽(yáng)性率顯著高于未浸潤(rùn)漿膜層、Lauren分型腸型、無(wú)脈管侵犯、無(wú)區(qū)域淋巴結(jié)轉(zhuǎn)移和早期的患者。4.KLF5主要表達(dá)于細(xì)胞質(zhì),呈棕褐色顆粒狀,在胃低分化腺癌組、中分化腺癌組、高分化腺癌組、高級(jí)別上皮內(nèi)瘤變組、低級(jí)別上皮內(nèi)瘤變組及正常胃黏膜組中的陽(yáng)性表達(dá)率分別為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),癌組織的陽(yáng)性率高于上皮內(nèi)瘤變組織和正常胃黏膜組織,陽(yáng)性表達(dá)率逐漸降低,但差異無(wú)統(tǒng)計(jì)學(xué)意義(χ2=7.35,P0.05)。5.在胃腺癌組織中,KLF5的陽(yáng)性表達(dá)與患者年齡、性別、腫瘤的部位、腫瘤的直徑、組織學(xué)分級(jí)、浸潤(rùn)深度、Lauren分型、是否侵犯脈管、區(qū)域淋巴結(jié)轉(zhuǎn)移情況及臨床分期均無(wú)關(guān),差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。6.在胃腺癌組織中,LPA2陽(yáng)性組和陰性組的患者中位生存時(shí)間分別為11.02個(gè)月和23.04個(gè)月,兩組比較死亡風(fēng)險(xiǎn)差別有統(tǒng)計(jì)學(xué)意義(HR=1.89,95%CI:1.11-3.63,P0.05)。7.在胃腺癌組織中,KLF5陽(yáng)性組和陰性組的患者中位生存時(shí)間分別為10.7個(gè)月和12.1個(gè)月,兩組比較死亡風(fēng)險(xiǎn)差別無(wú)統(tǒng)計(jì)學(xué)意義(HR=1.11,95%CI:0.53-2.363,P0.05)。8.在胃腺癌組織中,KLF5與LPA2蛋白的表達(dá)呈正相關(guān)性(γ=0.66,P0.05)。結(jié)論:1.LPA2蛋白在胃腺癌組織中高表達(dá),其陽(yáng)性表達(dá)與患者腫瘤的浸潤(rùn)深度、Lauren分型、是否侵犯脈管、區(qū)域淋巴結(jié)轉(zhuǎn)移情況及臨床分期有密切關(guān)系,提示LPA2可能參與胃腺癌的發(fā)生,并且可作為判斷胃腺癌發(fā)展、轉(zhuǎn)移的一個(gè)重要指標(biāo)。2.LPA2蛋白在胃腺癌中陽(yáng)性組患者較陰性組患者生存時(shí)間短,提示其檢測(cè)可能有助于評(píng)估胃腺癌患者的預(yù)后。3.KLF5與LPA2在胃腺癌組織中的表達(dá)呈正相關(guān),提示兩者間可能存在一種相互關(guān)聯(lián)的機(jī)制,從而在胃腺癌中發(fā)揮作用。
[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.
【學(xué)位授予單位】:蘭州大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2017
【分類號(hào)】:R735.2

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