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TYK2与P53在乳腺癌中的表达及临床意义

发布时间:2019-05-16 01:18
【摘要】:背景:乳腺癌是女性最常见的恶性肿瘤,严重危害着女性的健康和生命,新型特异性标志物的检测在乳腺癌早期诊断及治疗中发挥着重要作用。目前研究表明,TYK2(Tyrosine Kinase 2,酪氨酸激酶2)高表达可促进肿瘤细胞的增殖及侵袭能力,但其在乳腺癌发生与演变过程中的作用有细胞和组织特异性,有待深入研究。P53作为熟知的抑癌基因,在细胞周期、细胞凋亡等过程中起重要调控功能,而P53在肿瘤中发生突变则促进肿瘤的恶性发展。有研究表明,在肺癌细胞中诱导野生型P53表达可通过一种E3泛素连接酶SIAH2(seven-in-absentia-2)下调TYK2的表达,进而影响下游信号通路,这提示P53与TYK2之间存在调控现象。而TYK2、P53在乳腺癌中表达的相关性鲜有研究报道。目的:检测TYK2和P53在临床乳腺组织标本中的表达情况,分析其与患者年龄、绝经状态、淋巴结转移等病理特征间的关系及意义;探讨二者在乳腺癌中的表达是否相关,并阐明潜在的临床指导意义。方法:收集大连医科大学附属第二医院2013年09月-2016年09月期间行手术切除的乳腺病理组织标本152例,其中乳腺癌102例、纤维腺瘤30例、癌旁组织20例。采用免疫组织化学染色方法对TYK2和P53在三种不同乳腺组织中的表达情况进行检测,分析与临床病理特征之间的关系,探讨二者在乳腺癌中表达的相关性。结果:(1)TYK2在乳腺癌组织中高表达,阳性表达率为57.84%(59/102),高于乳腺纤维腺瘤组织(6.67%)及癌旁组织(0.00%);P53在乳腺癌组织中高表达,阳性表达率为40.20%(41/102),高于乳腺纤维腺瘤组织(3.33%)及癌旁组织(0.00%)。(2)TYK2在乳腺癌组织中的表达与肿瘤大小、临床分期、ER、PR及Ki-67状态相关(p0.05),而与患者年龄、绝经状态、淋巴结转移、有无脉管或神经侵犯、HER-2状态无显著相关性(p0.05)。P53在乳腺癌中的表达与淋巴结转移、ER、PR及Ki-67状态(p0.05)相关,而与患者年龄、绝经状态、肿瘤大小、有无脉管或神经侵犯、临床分期、HER-2状态无明显相关性(p0.05)。TYK2在乳腺癌各分子分型中的阳性表达率分别为42.31%(Luminal A型)、54.55(Luminal B型)、61.90%(HER-2过表达型)和77.27%(三阴性);P53的阳性表达率分别为19.23%(Luminal A型)、33.33%(Luminal B型)、42.86%(HER-2过表达型)和72.73%(三阴性);P53在三阴性乳腺癌中表达水平较高,有统计学差异(X2=15.148,p=0.002)。(3)经Spearman相关分析,TYK2和P53在乳腺癌总体样本中的表达具有正相关性(r=0.560,p=0.000)。结论:(1)TYK2和P53在乳腺癌中的表达高于乳腺纤维腺瘤组织及癌旁组织;P53在三阴性乳腺癌中的阳性表达率高于其他分子分型。(2)乳腺癌中TYK2的表达与肿瘤大小、临床分期、ER、PR及Ki-67状态相关;P53的表达与淋巴结转移、ER、PR及Ki-67状态相关。(3)TYK2和P53在乳腺癌中的表达有正相关性;联合检测二者的表达可为临床乳腺癌的诊断、治疗及预后评估等提供更准确的参考。
[Abstract]:Background: breast cancer is the most common malignant tumor in women, which seriously endangers the health and life of women. The detection of new specific markers plays an important role in the early diagnosis and treatment of breast cancer. Recent studies have shown that the high expression of TYK2 (Tyrosine Kinase 2 and tyrosine kinase 2) can promote the proliferation and invasion of tumor cells, but its role in the occurrence and evolution of breast cancer is cell and tissue specific. P53, as a well-known tumor suppressor gene, plays an important role in cell cycle, apoptosis and other processes, while p53 mutation in tumors promotes the malignant development of tumors. Some studies have shown that inducing the expression of wild type p53 in lung cancer cells can down-regulate the expression of TYK2 through an E3 ubiquitin ligase SIAH2 (seven-in-absentia-2), which may affect the downstream signal pathway, which suggests that there is a regulatory phenomenon between p53 and TYK2. However, the correlation of TYK2,P53 expression in breast cancer is rarely reported. Objective: to detect the expression of TYK2 and p53 in clinical breast tissues and analyze their relationship with pathological features such as age, menopausal status, lymph node metastasis and so on. To explore the relationship between the expression of the two in breast cancer and to elucidate the potential clinical significance. Methods: 152 cases of breast pathological tissue were collected from September 2013 to September 2016 in the second affiliated Hospital of Dalian Medical University, including 102 cases of breast cancer, 30 cases of fibroadenoma and 20 cases of paracancerous tissue. The expression of TYK2 and p53 in three different breast tissues was detected by immunohistochemical staining, and the relationship between the expression of p53 and clinicopathological features was analyzed, and the correlation between the expression of p53 and p53 in breast cancer was discussed. Results: (1) the positive expression rate of TYK2 in breast cancer was 57.84% (59 鈮,

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