Ki67、LRP在胃癌中的表達(dá)及其臨床意義
發(fā)布時(shí)間：2018-08-06 10:57
【摘要】：目的:我國(guó)人口的惡性腫瘤發(fā)病人數(shù)逐年上升,居民的健康和生命受到嚴(yán)重威脅,胃癌是較為常見(jiàn)的惡性腫瘤,其發(fā)病率在男性各類腫瘤中居第2位,在女性居第3位。據(jù)流行病學(xué)預(yù)測(cè),我國(guó)胃癌的發(fā)病率及死亡率在未來(lái)的20年均將呈現(xiàn)持續(xù)增長(zhǎng)趨勢(shì)。胃癌的發(fā)生、發(fā)展是多步驟、多環(huán)節(jié)、多基因參與并影響其發(fā)展及預(yù)后,由于缺乏便捷有效的普查手段,我國(guó)臨床收治的胃癌大多數(shù)為進(jìn)展期,對(duì)胃癌的早期診斷及有效治療已成為當(dāng)前一個(gè)亟待解決的問(wèn)題。有效的化療是延長(zhǎng)胃癌患者生存期的重要方法之一,也是近幾年研究的熱點(diǎn)。Gerdes等學(xué)者于1983年首次制備出了Ki67抗體,Ki67位于細(xì)胞核內(nèi),與其他已知的蛋白均不具有明顯的同源性,其與細(xì)胞的增殖活性有關(guān)。LRP是一種新的多藥耐藥相關(guān)蛋白,由Scheper等于1993年發(fā)現(xiàn),起初是從一株人小細(xì)胞肺癌多耐藥細(xì)胞中發(fā)現(xiàn),該蛋白表現(xiàn)為對(duì)藥物能量依賴性的蓄積能力下降。LRP存在于細(xì)胞質(zhì),是一種引起MDR的蛋白,其介導(dǎo)鉑類、烷化劑等耐藥[1],但LRP與胃癌預(yù)后報(bào)道很少。LRP與Ki67共同研究,分析二者的相關(guān)性及對(duì)胃癌的預(yù)后研究國(guó)內(nèi)文獻(xiàn)報(bào)道甚少。本實(shí)驗(yàn)采用免疫組化對(duì)胃癌組織、癌旁組織及正常胃粘膜組織進(jìn)行SP法染色,分析Ki67、LRP的表達(dá)率及其與病例的年齡、性別、腫瘤浸潤(rùn)深度、分化程度、TNM分期、淋巴結(jié)轉(zhuǎn)移等參數(shù)的相關(guān)性分析,從而為胃癌的預(yù)后判斷及化療提供可能性的理論依據(jù)。方法:隨機(jī)選取40例胃癌患者及20例因胃部疾病就診的非胃癌患者,實(shí)驗(yàn)標(biāo)本為胃癌組織(40例)、相應(yīng)癌旁5cm組織(40例)、正常胃粘膜組織(20例),采用免疫組織化學(xué)SP法檢測(cè)標(biāo)本中Ki67、LRP的表達(dá)率,并結(jié)合患者的性別、年齡、腫瘤浸潤(rùn)深度、分化程度、TNM分期行統(tǒng)計(jì)學(xué)分析,應(yīng)用χ2檢驗(yàn)對(duì)計(jì)數(shù)資料進(jìn)行分析,研究胃癌中Ki67、LRP表達(dá)的相關(guān)性因素。P0.05時(shí)差異有統(tǒng)計(jì)學(xué)意義。結(jié)果:1 Ki67陽(yáng)性表達(dá)為細(xì)胞核中可觀察到淡黃色、棕黃色或棕褐色顆粒,本研究顯示:Ki67在胃癌中的表達(dá)率為72.5%(29/40)、癌旁粘膜組織為45%(18/40)、正常胃粘膜組織中10%(2/20),組間的差異通過(guò)χ2檢驗(yàn)相關(guān)性分析顯示P0.05,具有統(tǒng)計(jì)學(xué)意義。2 LRP陽(yáng)性表達(dá)為細(xì)胞質(zhì)中可觀察到淡黃色、棕黃色或棕褐色顆粒,本研究顯示:LRP在胃癌的陽(yáng)性表達(dá)率為75%(30/40)、癌旁粘膜組織52.5%(21/40)、正常胃粘膜組織25%(5/20),三組間的差異通過(guò)χ2檢驗(yàn)相關(guān)性分析顯示P0.05,具有統(tǒng)計(jì)學(xué)意義。3胃癌組織中Ki67和LRP的表達(dá)與臨床病理因素的相關(guān)性分析3.1低分化胃癌組織中Ki67的表達(dá)率為85.19%(23/27),明顯高于高中分化的表達(dá)率46.15%(6/13)(P0.05)。I+II期胃癌中Ki67的表達(dá)率為50.00%(6/12),明顯低于III+IV期胃癌的表達(dá)率82.14%(23/28)(P0.05)。存在淋巴結(jié)轉(zhuǎn)移的胃癌組織中Ki67的陽(yáng)性表達(dá)率為82.14%(23/28),無(wú)淋巴結(jié)轉(zhuǎn)移的表達(dá)率50.00%(6/12),兩者之間差異具有統(tǒng)計(jì)學(xué)意義(P0.05)。Ki67的表達(dá)與患者的年齡、性別的差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。3.2 LRP蛋白在高中分化胃癌組織中的表達(dá)率為61.54%(8/13),明顯低于低分化的表達(dá)率81.48%(22/27),但P0.05。LRP的表達(dá)在患者的年齡、性別、腫瘤分化程度、浸潤(rùn)深度、TNM分期、淋巴結(jié)轉(zhuǎn)移參數(shù)的差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。4運(yùn)用χ2檢驗(yàn)相關(guān)分析,結(jié)果表明Ki67和LRP蛋白的表達(dá)無(wú)相關(guān)性(P0.05)。結(jié)論:1在胃癌中,Ki67呈高表達(dá),與分化程度、浸潤(rùn)深度、TNM分期、淋巴結(jié)轉(zhuǎn)移相關(guān),與患者的年齡、性別無(wú)相關(guān)性。Ki67與腫瘤細(xì)胞的分化程度等生物學(xué)習(xí)性有關(guān),可反映腫瘤的活性及進(jìn)展?fàn)顟B(tài)。2在胃癌中,LRP呈高表達(dá),與腫瘤浸潤(rùn)深度、分化程度、TNM分期、淋巴結(jié)轉(zhuǎn)移以及患者的年齡、性別無(wú)相關(guān)性。但LRP在腫瘤細(xì)胞中表達(dá)高于正常胃組織,這提示胃癌的發(fā)生與LRP表達(dá)上調(diào)有關(guān),可反映LRP對(duì)胃癌的原發(fā)性耐藥性起重要作用。3在胃癌中,Ki67和LRP的表達(dá)無(wú)明顯相關(guān)性,但兩者可從腫瘤細(xì)胞的增殖、發(fā)展程度與原發(fā)耐藥性方面綜合評(píng)估腫瘤的發(fā)展,間接評(píng)估腫瘤預(yù)后,并為化療用藥提供指導(dǎo)方案。
[Abstract]:Objective: the number of malignant tumors in the population is rising year by year, and the health and life of the residents are seriously threatened. Gastric cancer is the most common malignant tumor. The incidence of the cancer is second in all kinds of male tumors and third in women. According to the epidemiological prediction, the incidence and mortality of gastric cancer in China will continue to continue in the next 20 years. The growth trend. The occurrence and development of gastric cancer is a multistep, multi link, multi gene participation and influence on its development and prognosis. Due to the lack of convenient and effective survey methods, most of the clinical gastric cancer in our country is progressing stage. Early diagnosis and effective treatment of gastric cancer have become an urgent problem to be solved. Effective chemotherapy is the prolongation of the stomach. One of the important methods of cancer patient's survival time is also a hot spot in recent years,.Gerdes and other scholars have prepared Ki67 antibody for the first time. Ki67 is in the nucleus and does not have obvious homology with other known proteins..LRP is a new multidrug resistance related protein related to cell proliferation activity, which is equal to 199 by Scheper. 3 years later, it was found that it was found in a human small cell lung cancer multidrug resistant cell, which showed that the accumulative capacity of the drug energy dependent decreased.LRP existed in the cytoplasm. It is a protein that causes MDR, which mediates the platinum, alkylating agents, and other drug resistant [1]. However, there are few reports of.LRP and Ki67 in the report of LRP and gastric cancer, and the analysis of the phase of the two. There are few domestic literature reports on the prognosis of gastric cancer. In this experiment, immunohistochemical method was used to stain gastric cancer tissue, para cancer tissue and normal gastric mucosa by SP staining. The expression rate of Ki67, LRP and the correlation analysis of age, sex, tumor invasion depth, differentiation range, TNM staging, lymph node metastasis were analyzed. The theoretical basis of the prognosis of gastric cancer and the possibility of chemotherapy was provided. Methods: 40 cases of gastric cancer and 20 non gastric cancer patients with gastric disease were randomly selected, the experimental specimens were gastric cancer tissue (40 cases), corresponding 5cm tissues (40 cases) and normal gastric mucosa (20 cases), and immunohistochemistry SP method was used to detect Ki67, LRP The rate of expression was combined with the sex, age, depth of invasion, degree of differentiation and TNM staging of the patients. The count data were analyzed by chi 2 test, and the correlation factor of Ki67 and LRP expression in gastric cancer was statistically significant. The results were that the positive expression of 1 Ki67 was that the nucleus could be observed to be yellowish and brown in the nucleus. The present study showed that the expression rate of Ki67 in gastric cancer was 72.5% (29/40), the mucosa adjacent to the carcinoma was 45% (18/40), and 10% (2/20) in the normal gastric mucosa. The difference between the groups showed P0.05 by the chi square 2 test correlation analysis, and the positive expression of.2 LRP could be observed in the cytoplasm of the pale yellow, brown, or brownish brown. The positive rate of LRP in gastric cancer was 75% (30/40), 52.5% (21/40) and 25% (5/20) in normal gastric mucosa, and the difference between three groups showed P0.05 by chi 2 test correlation analysis. The correlation between the expression of Ki67 and LRP in gastric cancer tissues and the correlation analysis of clinicopathological factors was 3.1 low scores. The expression rate of Ki67 in gastric carcinoma was 85.19% (23/27), which was significantly higher than the expression rate of high school differentiation 46.15% (6/13) (6/13). The expression rate of Ki67 was 50% (6/12) in.I+II stage gastric cancer, and was significantly lower than that of III+IV stage gastric carcinoma (23/28) (23/28) (P0.05). The positive expression rate of Ki67 in gastric carcinoma with lymph node metastasis was 82.14% (23/28). The expression rate of the metastasis was 50% (6/12). The difference was statistically significant (P0.05).Ki67 expression and the age of the patients. There was no significant difference in sex (P0.05) the expression rate of.3.2 LRP protein in high school differentiated gastric carcinoma was 61.54% (8/13), and the expression rate was lower than that of low differentiation 81.48% (22/27), but the expression of P0.05.LRP was in the expression of 81.48% (22/27). The age, sex, tumor differentiation, depth of invasion, depth of infiltration, TNM staging, and lymph node metastasis were not statistically significant (P0.05).4 using chi 2 test correlation analysis, the results showed that the expression of Ki67 and LRP protein was not correlated (P0.05). Conclusion: the expression of Ki67 in gastric cancer is high, with the degree of differentiation, depth of infiltration, TNM staging, lymph node metastasis. Correlation, related to the age, sex independent.Ki67 of the patient and the degree of differentiation of tumor cells, which can reflect the activity and progression of the tumor, and the progression state of.2 is highly expressed in gastric cancer, with the depth of the tumor, the degree of differentiation, the TNM staging, the lymph node metastasis and the age and sex of the patient, but LRP is in the tumor cells. The expression is higher than normal gastric tissue, which suggests that the occurrence of gastric cancer is related to the up regulation of LRP expression, which can reflect the important role of LRP in the primary drug resistance of gastric cancer,.3 in gastric cancer, there is no significant correlation between the expression of Ki67 and LRP, but both can evaluate the development of tumor from the proliferation of tumor cells, the degree of development and the primary drug resistance, and indirectly evaluate the development of the tumor. To estimate tumor prognosis and provide guidance for chemotherapy.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R735.2
本文編號(hào)：2167519
[Abstract]:Objective: the number of malignant tumors in the population is rising year by year, and the health and life of the residents are seriously threatened. Gastric cancer is the most common malignant tumor. The incidence of the cancer is second in all kinds of male tumors and third in women. According to the epidemiological prediction, the incidence and mortality of gastric cancer in China will continue to continue in the next 20 years. The growth trend. The occurrence and development of gastric cancer is a multistep, multi link, multi gene participation and influence on its development and prognosis. Due to the lack of convenient and effective survey methods, most of the clinical gastric cancer in our country is progressing stage. Early diagnosis and effective treatment of gastric cancer have become an urgent problem to be solved. Effective chemotherapy is the prolongation of the stomach. One of the important methods of cancer patient's survival time is also a hot spot in recent years,.Gerdes and other scholars have prepared Ki67 antibody for the first time. Ki67 is in the nucleus and does not have obvious homology with other known proteins..LRP is a new multidrug resistance related protein related to cell proliferation activity, which is equal to 199 by Scheper. 3 years later, it was found that it was found in a human small cell lung cancer multidrug resistant cell, which showed that the accumulative capacity of the drug energy dependent decreased.LRP existed in the cytoplasm. It is a protein that causes MDR, which mediates the platinum, alkylating agents, and other drug resistant [1]. However, there are few reports of.LRP and Ki67 in the report of LRP and gastric cancer, and the analysis of the phase of the two. There are few domestic literature reports on the prognosis of gastric cancer. In this experiment, immunohistochemical method was used to stain gastric cancer tissue, para cancer tissue and normal gastric mucosa by SP staining. The expression rate of Ki67, LRP and the correlation analysis of age, sex, tumor invasion depth, differentiation range, TNM staging, lymph node metastasis were analyzed. The theoretical basis of the prognosis of gastric cancer and the possibility of chemotherapy was provided. Methods: 40 cases of gastric cancer and 20 non gastric cancer patients with gastric disease were randomly selected, the experimental specimens were gastric cancer tissue (40 cases), corresponding 5cm tissues (40 cases) and normal gastric mucosa (20 cases), and immunohistochemistry SP method was used to detect Ki67, LRP The rate of expression was combined with the sex, age, depth of invasion, degree of differentiation and TNM staging of the patients. The count data were analyzed by chi 2 test, and the correlation factor of Ki67 and LRP expression in gastric cancer was statistically significant. The results were that the positive expression of 1 Ki67 was that the nucleus could be observed to be yellowish and brown in the nucleus. The present study showed that the expression rate of Ki67 in gastric cancer was 72.5% (29/40), the mucosa adjacent to the carcinoma was 45% (18/40), and 10% (2/20) in the normal gastric mucosa. The difference between the groups showed P0.05 by the chi square 2 test correlation analysis, and the positive expression of.2 LRP could be observed in the cytoplasm of the pale yellow, brown, or brownish brown. The positive rate of LRP in gastric cancer was 75% (30/40), 52.5% (21/40) and 25% (5/20) in normal gastric mucosa, and the difference between three groups showed P0.05 by chi 2 test correlation analysis. The correlation between the expression of Ki67 and LRP in gastric cancer tissues and the correlation analysis of clinicopathological factors was 3.1 low scores. The expression rate of Ki67 in gastric carcinoma was 85.19% (23/27), which was significantly higher than the expression rate of high school differentiation 46.15% (6/13) (6/13). The expression rate of Ki67 was 50% (6/12) in.I+II stage gastric cancer, and was significantly lower than that of III+IV stage gastric carcinoma (23/28) (23/28) (P0.05). The positive expression rate of Ki67 in gastric carcinoma with lymph node metastasis was 82.14% (23/28). The expression rate of the metastasis was 50% (6/12). The difference was statistically significant (P0.05).Ki67 expression and the age of the patients. There was no significant difference in sex (P0.05) the expression rate of.3.2 LRP protein in high school differentiated gastric carcinoma was 61.54% (8/13), and the expression rate was lower than that of low differentiation 81.48% (22/27), but the expression of P0.05.LRP was in the expression of 81.48% (22/27). The age, sex, tumor differentiation, depth of invasion, depth of infiltration, TNM staging, and lymph node metastasis were not statistically significant (P0.05).4 using chi 2 test correlation analysis, the results showed that the expression of Ki67 and LRP protein was not correlated (P0.05). Conclusion: the expression of Ki67 in gastric cancer is high, with the degree of differentiation, depth of infiltration, TNM staging, lymph node metastasis. Correlation, related to the age, sex independent.Ki67 of the patient and the degree of differentiation of tumor cells, which can reflect the activity and progression of the tumor, and the progression state of.2 is highly expressed in gastric cancer, with the depth of the tumor, the degree of differentiation, the TNM staging, the lymph node metastasis and the age and sex of the patient, but LRP is in the tumor cells. The expression is higher than normal gastric tissue, which suggests that the occurrence of gastric cancer is related to the up regulation of LRP expression, which can reflect the important role of LRP in the primary drug resistance of gastric cancer,.3 in gastric cancer, there is no significant correlation between the expression of Ki67 and LRP, but both can evaluate the development of tumor from the proliferation of tumor cells, the degree of development and the primary drug resistance, and indirectly evaluate the development of the tumor. To estimate tumor prognosis and provide guidance for chemotherapy.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R735.2
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