FN1與miR-671-3p在乳腺癌中的表達(dá)、二者相關(guān)性及臨床意義的研究
發(fā)布時(shí)間：2018-09-01 20:34
【摘要】：背景：纖維連接蛋白1(Fibronectin 1, FN1)是一種重要的細(xì)胞外基質(zhì)(extracellular matrix, ECM)分子,參與了基質(zhì)重塑及細(xì)胞黏附和遷移過(guò)程,其通過(guò)調(diào)節(jié)肌動(dòng)蛋白聚合而影響細(xì)胞的運(yùn)動(dòng)。2012年的文獻(xiàn)報(bào)道提示在三陰乳腺癌細(xì)胞系MDA-MB-231中FN1為miR-671-3p潛在的靶基因,miR-671-3p具有抑制侵襲和細(xì)胞粘附的作用。但目前FN1和miR-671-3p在乳腺癌中的表達(dá)報(bào)道均存在爭(zhēng)議,部分文獻(xiàn)提示FN1在乳腺癌組織和細(xì)胞中高表達(dá),但也有文獻(xiàn)提示其低表達(dá),miR-671-3p在三陰乳腺癌細(xì)胞系的研究中提示低表達(dá),而2013年一項(xiàng)大規(guī)模的乳腺癌患者血清學(xué)樣本研究提示其高表達(dá)。目的：探討FN1及miR-671-3p在乳腺癌中的表達(dá)、二者的相關(guān)性及臨床意義。方法：①通過(guò)免疫組化SupervisionTM二步法檢測(cè)81例乳腺癌和其中相應(yīng)的40例癌旁組織中FN1蛋白的表達(dá),比較FN1與年齡、腫瘤大小、淋巴結(jié)轉(zhuǎn)移、臨床分期、分子亞型表達(dá)等臨床病理參數(shù)及ER/PR、HER2、Ki-67、 p53、p16、Vimentin指標(biāo)的關(guān)系,繪制ROC曲線評(píng)價(jià)FN1對(duì)乳腺癌及乳腺癌的淋巴結(jié)轉(zhuǎn)移的診斷價(jià)值,收集隨訪資料,判斷FN1對(duì)預(yù)后的價(jià)值；②進(jìn)行文獻(xiàn)分析并運(yùn)用生物信息學(xué)網(wǎng)站microRNA. org、TargetScan、HOCTAR、 miRDB、EMBL-EBI對(duì)調(diào)節(jié)FN1的miRNA進(jìn)行預(yù)測(cè),選定1個(gè)miRNA行進(jìn)一步研究；③RT-qPCR檢測(cè)上述石蠟組織中49例乳腺癌和13例癌旁組織miR-671-3p的表達(dá),比較其與上述臨床病理參數(shù)及指標(biāo)的關(guān)系,繪制ROC曲線評(píng)價(jià)miR-671-3p對(duì)乳腺癌及乳腺癌的淋巴結(jié)轉(zhuǎn)移的診斷價(jià)值,進(jìn)行生存分析,判斷miR-671-3p對(duì)預(yù)后的影響；④比較FN1與miR-671-3p二者的表達(dá)關(guān)系。結(jié)果：①FN1在乳腺癌細(xì)胞和間質(zhì)中的表達(dá)明顯高于癌旁腺上皮和間質(zhì)(均P0.001),而在癌組織基底膜中的表達(dá)則明顯低于癌旁(P0.001)；FN1表達(dá)水平與組織學(xué)分級(jí)(r=0.385,P=0.001)、腫瘤大小(r=0.270,P=0.015)、淋巴結(jié)轉(zhuǎn)移(r=0.335,P=0.002)、臨床分期(r=0.482,P=0.000)、HER2的表達(dá)(r=0.237,P=0.033)呈正相關(guān)；與ER/PR(r=-0.309,P=0.005)、p53(r=-0.234,P=0.035)呈負(fù)相關(guān)；FN1的表達(dá)在分子亞型中存在差異(P0.05),在HER2過(guò)表達(dá)型中明顯高于Lumin al型(P0.01)；FN1診斷乳腺癌的ROC曲線下面積為0.927,診斷淋巴結(jié)轉(zhuǎn)移的ROC曲線下面積為0.631,診斷價(jià)值優(yōu)于Ki-67、p53、p16、Vimentin。乳腺癌3年生存率81%,與腫瘤大小(P=0.048)相關(guān)；FN1高表達(dá)、ER/PR陰性、HER2過(guò)表達(dá)、p16陽(yáng)性和較差的臨床分期與乳腺癌3年低生存率存在一定關(guān)系,但未達(dá)到統(tǒng)計(jì)學(xué)差異(P=0.071,0.060,0.055,0.079,0.101)。②篩選出miR-671-3p進(jìn)行進(jìn)一步研究。③miR-671-3p在癌組織中的表達(dá)有低于癌旁的趨勢(shì),在三陰型中有低表達(dá)的趨勢(shì),但未達(dá)到統(tǒng)計(jì)學(xué)差異(P0.05)；miR-671-3p在余臨床病理參數(shù)、Ki-67、p53、p16、Vimentin等指標(biāo)不同亞組中的表達(dá)也均無(wú)統(tǒng)計(jì)學(xué)差異(P0.05)；miR-671-3p診斷乳腺癌的ROC曲線下面積為0.519(P0.05),診斷乳腺癌淋巴結(jié)轉(zhuǎn)移的曲線下面積為0.565(P0.05),但P0.05,尚不能認(rèn)為miR-671-3p對(duì)乳腺癌及乳腺癌淋巴結(jié)轉(zhuǎn)移的具有診斷價(jià)值。miR-671-3p低表達(dá)組死亡2例(2/25),生存均值31.444個(gè)月,miR-671-3p高表達(dá)死亡1例(1/24),生存均值33.818月。miR-671-3p低表達(dá)與乳腺癌3年低生存率存在一定關(guān)系,但未達(dá)到統(tǒng)計(jì)學(xué)差異(P=0.474)。④FN1與miR-671-3p二者的表達(dá)在乳腺癌組織(r=-0.185,P=0.20)及分子亞型三陰型中(r=-0.523,P=0.081)存在負(fù)相關(guān)的趨勢(shì),但未達(dá)到統(tǒng)計(jì)學(xué)差異,尚不能認(rèn)為FN1與miR-671-3p二者的表達(dá)不存在相關(guān)性。結(jié)論：①FN1的異常表達(dá)可能在乳腺癌的發(fā)生,淋巴結(jié)轉(zhuǎn)移,分子亞型的轉(zhuǎn)移能力和疾病的惡性進(jìn)展中起重要作用。FN1有望成為判斷疾病進(jìn)展的生物學(xué)標(biāo)記。②miR-671-3p在癌組織中及三陰型中有低表達(dá)的趨勢(shì),miR-671-3p低表達(dá)與乳腺癌3年低生存率可能存在一定關(guān)系。FN1與miR-671-3p二者的表達(dá)在乳腺癌組織及分子亞型三陰型中存在負(fù)相關(guān)的趨勢(shì)。綜上所述,乳腺癌中,miR-671-3p作為生物學(xué)標(biāo)記的價(jià)值需進(jìn)一步證實(shí)。
[Abstract]:BACKGROUND: Fibronectin 1 (FN1) is an important extracellular matrix (ECM) molecule involved in matrix remodeling, cell adhesion and migration, which affects cell movement by regulating actin aggregation. The 2012 literature suggests that FN1 in tri-negative breast cancer cell line MDA-MB-231 is Mi-671-3p is a potential target gene for microarray-671-3p, which can inhibit invasion and cell adhesion. However, the expression of FN1 and microarray-671-3p in breast cancer is controversial. Some literatures suggest that FN1 is highly expressed in breast cancer tissues and cells, but there are also literature suggesting its low expression. Mi-671-3p is used in the study of triple-negative breast cancer cell lines. Objective: To investigate the expression of FN1 and microRNA671-3p in breast cancer and their correlation and clinical significance. Methods: Immunohistochemical SupervisionTM two-step method was used to detect 81 cases of breast cancer and 40 cases of adjacent tissues. Expression of FN1 protein was compared with age, tumor size, lymph node metastasis, clinical stage, molecular subtype expression and ER/PR, HER2, Ki-67, p53, p16, Vimentin. ROC curve was drawn to evaluate the diagnostic value of FN1 for lymph node metastasis of breast cancer and breast cancer. Follow-up data were collected to determine the prognostic value of FN1. (2) To analyze the literature and use the bioinformatics website microRNA.org, TargetScan, HOCTAR, microDB, EMBL-EBI to predict the regulation of FN1 microNA and select one microNA for further study; (3) RT-qPCR was used to detect the expression of microRNA-671-3p in 49 cases of breast cancer and 13 cases of adjacent tissues in paraffin-embedded paraffin-embedded tissues, and compared with the above clinicopathological parameters. ROC curves were drawn to evaluate the diagnostic value of microRNAs-671-3p in lymph node metastasis of breast cancer and breast cancer, and survival analysis was conducted to determine the prognostic effect of microRNAs-671-3p. The relationship between the expression of FN1 and microRNAs-671-3p was compared. The expression of FN1 was positively correlated with histological grade (r = 0.385, P = 0.001), tumor size (r = 0.270, P = 0.015), lymph node metastasis (r = 0.335, P = 0.002), clinical stage (r = 0.482, P = 0.000), HER2 expression (r = 0.237, P = 0.033), and ER/PR (r = - 0.309, P = 0.00). 5) p53 (r = - 0.234, P = 0.035) was negatively correlated; the expression of FN1 was significantly higher in HER2 overexpression than Lumin al (P 0.01); the area under ROC curve was 0.927 in FN1 diagnosis of breast cancer and 0.631 in diagnosis of lymph node metastasis, which was superior to Ki-67, p53, p16, Vimentin. Survival rate was 81%, which was related to tumor size (P = 0.048); high expression of FN1, negative expression of ER / PR, overexpression of HER2, positive and poor clinical stages of p16 were associated with 3-year low survival rate of breast cancer, but did not reach statistical difference (P = 0.071, 0.060, 0.055, 0.079, 0.101). 2. Mi-671-3p was screened out for further study. 3. Mi-671-3p was found in cancer tissues. The expression of Mi-671-3p was lower than that of adjacent cancer, but the expression of Mi-671-3p was lower than that of adjacent cancer, but the difference was not statistically significant (P 0.05); the expression of Mi-671-3p in other clinical and pathological parameters, such as Ki-67, p53, p16, Vimentin, was not statistically significant (P 0.05); the area under ROC curve of Mi-671-3p in the diagnosis of breast cancer was 0.519 (P 0.05). The area under the curve of breast cancer lymph node metastasis was 0.565 (P 0.05), but P 0.05. It was not considered that microRNA671-3p had diagnostic value for breast cancer and breast cancer lymph node metastasis. There was a negative correlation between FN1 and microRNA671-3p expression in breast cancer tissues (r = - 0.185, P = 0.20) and molecular subtypes (r = - 0.523, P = 0.081), but there was no significant difference between FN1 and microRNA671-3p expression. Conclusion: Abnormal expression of FN1 may play an important role in the occurrence, lymph node metastasis, metastatic ability of molecular subtypes and malignant progression of breast cancer. FN1 is expected to become a biological marker for judging the progress of the disease. The expression of FN1 and miR-671-3p may be negatively correlated with the three-year low survival rate of breast cancer.
【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類(lèi)號(hào)】：R737.9
本文編號(hào)：2218277
[Abstract]:BACKGROUND: Fibronectin 1 (FN1) is an important extracellular matrix (ECM) molecule involved in matrix remodeling, cell adhesion and migration, which affects cell movement by regulating actin aggregation. The 2012 literature suggests that FN1 in tri-negative breast cancer cell line MDA-MB-231 is Mi-671-3p is a potential target gene for microarray-671-3p, which can inhibit invasion and cell adhesion. However, the expression of FN1 and microarray-671-3p in breast cancer is controversial. Some literatures suggest that FN1 is highly expressed in breast cancer tissues and cells, but there are also literature suggesting its low expression. Mi-671-3p is used in the study of triple-negative breast cancer cell lines. Objective: To investigate the expression of FN1 and microRNA671-3p in breast cancer and their correlation and clinical significance. Methods: Immunohistochemical SupervisionTM two-step method was used to detect 81 cases of breast cancer and 40 cases of adjacent tissues. Expression of FN1 protein was compared with age, tumor size, lymph node metastasis, clinical stage, molecular subtype expression and ER/PR, HER2, Ki-67, p53, p16, Vimentin. ROC curve was drawn to evaluate the diagnostic value of FN1 for lymph node metastasis of breast cancer and breast cancer. Follow-up data were collected to determine the prognostic value of FN1. (2) To analyze the literature and use the bioinformatics website microRNA.org, TargetScan, HOCTAR, microDB, EMBL-EBI to predict the regulation of FN1 microNA and select one microNA for further study; (3) RT-qPCR was used to detect the expression of microRNA-671-3p in 49 cases of breast cancer and 13 cases of adjacent tissues in paraffin-embedded paraffin-embedded tissues, and compared with the above clinicopathological parameters. ROC curves were drawn to evaluate the diagnostic value of microRNAs-671-3p in lymph node metastasis of breast cancer and breast cancer, and survival analysis was conducted to determine the prognostic effect of microRNAs-671-3p. The relationship between the expression of FN1 and microRNAs-671-3p was compared. The expression of FN1 was positively correlated with histological grade (r = 0.385, P = 0.001), tumor size (r = 0.270, P = 0.015), lymph node metastasis (r = 0.335, P = 0.002), clinical stage (r = 0.482, P = 0.000), HER2 expression (r = 0.237, P = 0.033), and ER/PR (r = - 0.309, P = 0.00). 5) p53 (r = - 0.234, P = 0.035) was negatively correlated; the expression of FN1 was significantly higher in HER2 overexpression than Lumin al (P 0.01); the area under ROC curve was 0.927 in FN1 diagnosis of breast cancer and 0.631 in diagnosis of lymph node metastasis, which was superior to Ki-67, p53, p16, Vimentin. Survival rate was 81%, which was related to tumor size (P = 0.048); high expression of FN1, negative expression of ER / PR, overexpression of HER2, positive and poor clinical stages of p16 were associated with 3-year low survival rate of breast cancer, but did not reach statistical difference (P = 0.071, 0.060, 0.055, 0.079, 0.101). 2. Mi-671-3p was screened out for further study. 3. Mi-671-3p was found in cancer tissues. The expression of Mi-671-3p was lower than that of adjacent cancer, but the expression of Mi-671-3p was lower than that of adjacent cancer, but the difference was not statistically significant (P 0.05); the expression of Mi-671-3p in other clinical and pathological parameters, such as Ki-67, p53, p16, Vimentin, was not statistically significant (P 0.05); the area under ROC curve of Mi-671-3p in the diagnosis of breast cancer was 0.519 (P 0.05). The area under the curve of breast cancer lymph node metastasis was 0.565 (P 0.05), but P 0.05. It was not considered that microRNA671-3p had diagnostic value for breast cancer and breast cancer lymph node metastasis. There was a negative correlation between FN1 and microRNA671-3p expression in breast cancer tissues (r = - 0.185, P = 0.20) and molecular subtypes (r = - 0.523, P = 0.081), but there was no significant difference between FN1 and microRNA671-3p expression. Conclusion: Abnormal expression of FN1 may play an important role in the occurrence, lymph node metastasis, metastatic ability of molecular subtypes and malignant progression of breast cancer. FN1 is expected to become a biological marker for judging the progress of the disease. The expression of FN1 and miR-671-3p may be negatively correlated with the three-year low survival rate of breast cancer.
【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類(lèi)號(hào)】：R737.9
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