FN1与miR-671-3p在乳腺癌中的表达、二者相关性及临床意义的研究
发布时间：2018-09-01 20:34
【摘要】：背景：纤维连接蛋白1(Fibronectin 1, FN1)是一种重要的细胞外基质(extracellular matrix, ECM)分子,参与了基质重塑及细胞黏附和迁移过程,其通过调节肌动蛋白聚合而影响细胞的运动。2012年的文献报道提示在三阴乳腺癌细胞系MDA-MB-231中FN1为miR-671-3p潜在的靶基因,miR-671-3p具有抑制侵袭和细胞粘附的作用。但目前FN1和miR-671-3p在乳腺癌中的表达报道均存在争议,部分文献提示FN1在乳腺癌组织和细胞中高表达,但也有文献提示其低表达,miR-671-3p在三阴乳腺癌细胞系的研究中提示低表达,而2013年一项大规模的乳腺癌患者血清学样本研究提示其高表达。目的：探讨FN1及miR-671-3p在乳腺癌中的表达、二者的相关性及临床意义。方法：①通过免疫组化SupervisionTM二步法检测81例乳腺癌和其中相应的40例癌旁组织中FN1蛋白的表达,比较FN1与年龄、肿瘤大小、淋巴结转移、临床分期、分子亚型表达等临床病理参数及ER/PR、HER2、Ki-67、 p53、p16、Vimentin指标的关系,绘制ROC曲线评价FN1对乳腺癌及乳腺癌的淋巴结转移的诊断价值,收集随访资料,判断FN1对预后的价值；②进行文献分析并运用生物信息学网站microRNA. org、TargetScan、HOCTAR、 miRDB、EMBL-EBI对调节FN1的miRNA进行预测,选定1个miRNA行进一步研究；③RT-qPCR检测上述石蜡组织中49例乳腺癌和13例癌旁组织miR-671-3p的表达,比较其与上述临床病理参数及指标的关系,绘制ROC曲线评价miR-671-3p对乳腺癌及乳腺癌的淋巴结转移的诊断价值,进行生存分析,判断miR-671-3p对预后的影响；④比较FN1与miR-671-3p二者的表达关系。结果：①FN1在乳腺癌细胞和间质中的表达明显高于癌旁腺上皮和间质(均P0.001),而在癌组织基底膜中的表达则明显低于癌旁(P0.001)；FN1表达水平与组织学分级(r=0.385,P=0.001)、肿瘤大小(r=0.270,P=0.015)、淋巴结转移(r=0.335,P=0.002)、临床分期(r=0.482,P=0.000)、HER2的表达(r=0.237,P=0.033)呈正相关；与ER/PR(r=-0.309,P=0.005)、p53(r=-0.234,P=0.035)呈负相关；FN1的表达在分子亚型中存在差异(P0.05),在HER2过表达型中明显高于Lumin al型(P0.01)；FN1诊断乳腺癌的ROC曲线下面积为0.927,诊断淋巴结转移的ROC曲线下面积为0.631,诊断价值优于Ki-67、p53、p16、Vimentin。乳腺癌3年生存率81%,与肿瘤大小(P=0.048)相关；FN1高表达、ER/PR阴性、HER2过表达、p16阳性和较差的临床分期与乳腺癌3年低生存率存在一定关系,但未达到统计学差异(P=0.071,0.060,0.055,0.079,0.101)。②筛选出miR-671-3p进行进一步研究。③miR-671-3p在癌组织中的表达有低于癌旁的趋势,在三阴型中有低表达的趋势,但未达到统计学差异(P0.05)；miR-671-3p在余临床病理参数、Ki-67、p53、p16、Vimentin等指标不同亚组中的表达也均无统计学差异(P0.05)；miR-671-3p诊断乳腺癌的ROC曲线下面积为0.519(P0.05),诊断乳腺癌淋巴结转移的曲线下面积为0.565(P0.05),但P0.05,尚不能认为miR-671-3p对乳腺癌及乳腺癌淋巴结转移的具有诊断价值。miR-671-3p低表达组死亡2例(2/25),生存均值31.444个月,miR-671-3p高表达死亡1例(1/24),生存均值33.818月。miR-671-3p低表达与乳腺癌3年低生存率存在一定关系,但未达到统计学差异(P=0.474)。④FN1与miR-671-3p二者的表达在乳腺癌组织(r=-0.185,P=0.20)及分子亚型三阴型中(r=-0.523,P=0.081)存在负相关的趋势,但未达到统计学差异,尚不能认为FN1与miR-671-3p二者的表达不存在相关性。结论：①FN1的异常表达可能在乳腺癌的发生,淋巴结转移,分子亚型的转移能力和疾病的恶性进展中起重要作用。FN1有望成为判断疾病进展的生物学标记。②miR-671-3p在癌组织中及三阴型中有低表达的趋势,miR-671-3p低表达与乳腺癌3年低生存率可能存在一定关系。FN1与miR-671-3p二者的表达在乳腺癌组织及分子亚型三阴型中存在负相关的趋势。综上所述,乳腺癌中,miR-671-3p作为生物学标记的价值需进一步证实。
[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.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R737.9
本文编号：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.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R737.9
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