多发性骨髓瘤患者骨髓单个核细胞CT7表达与临床相关性研究

发布时间：2018-01-12 04:10

本文关键词：多发性骨髓瘤患者骨髓单个核细胞CT7表达与临床相关性研究　出处：《东南大学》2015年硕士论文　论文类型：学位论文

【摘要】：背景：多发性骨髓瘤是血液系统恶性肿瘤,其发病率约占血液系统恶性肿瘤的13%,其特征是病态浆细胞在骨髓及其他造血组织中广泛的异常增生及浸润其他组织器官,导致广泛骨质破坏、贫血、单克隆球蛋白或游离轻链增多、肾功能损害等,目前仍是不可治愈的疾病。寻找并确认多发性骨髓瘤发生发展过程中的重要分子靶点和影响因子,并对其进行适当干预,诱导肿瘤细胞凋亡,分化或调节其增生,减慢疾病的发展速度而达到治疗效果,仍是现在的研究热点。癌睾丸抗原7(cancer testis antigens 7, CT7)是癌睾丸抗原(cancer testis antigens, CTAs)家族中的重要成员,其在多发性骨髓瘤患者浆细胞中广泛且高强度表达,很有希望用于骨髓瘤的疾病评估和治疗。目的：(1)探究CT7的表达与多发性骨髓瘤患者肿瘤负荷相关指标、临床分期的相关性。(2)分析CT7在初发、复发以及不同疗效的多发性骨髓瘤患者骨髓单个核细胞中的不同表达,明确CT7与疾病预后的相关性。(3)探讨CT7的表达与否对多发性骨髓瘤患者治疗疗效是否影响。方法：收集不同分期、初发及复发的骨髓瘤患者骨髓单个核细胞和骨髓活检标本,分别应用qPCR和免疫组化方法检测CT7的表达水平,同时收集患者相关的临床资料,分析CT7的表达水平与骨髓瘤临床指标、分期、预后、治疗(硼替佐米)的相关性。结果：(1)本研究共收集来自80例确诊为多发性骨髓瘤患者,患者平均年龄为61.01±10.887岁,男女比例为40/40,IgG型33例,IgA型24例,轻链型16例及其他少见类型7例。共收集骨髓瘤患者标本111份,其中初发标本43份,治疗后标本68份。(2)在多发性骨髓瘤患者骨髓单个核细胞中,CT7在mRNA和蛋白水平均有不同程度的表达,总体表达阳性率为72.97%(81/111),其中PCR检测阳性率为79.1%(68/86),免疫组化方法检测阳性率为54.3%(19/35)。CT7的mRNA表达与患者骨髓浆细胞比例、血清M蛋白呈正相关,其r值分别为0.345、0.442(p均0.01),与β2-微球蛋白、ISS分期具有显著相关性(p均0.05)。CT7的蛋白表达与骨髓浆细胞比例具有相关性(p=0.03)。(3)在治疗无效以及复发的患者中,其CT7蛋白表达阳性率明显高于治疗有效的患者,其分别为83.3%、80.0%、10.0%(p=0.002)(4)在随访的40例MM患者中,CT7表达阳性的患者治疗缓解率明显低于CT7表达阴性的患者(68.5%vs100%,p=0.02),其中23例使用硼替佐米化疗得患者中,CT7表达阳性和阴性的患者的治疗缓解率无显著性差异(84.2%vs100%,p=0.266)。结论：本研究发现CT7基因在多发性骨髓瘤患者骨髓单个核细胞中广泛表达,与浆细胞比例、M蛋白、β2-微球蛋白等肿瘤负荷指标相关,在治疗效果差和复发的患者中表达显著,并且CT7表达阳性的患者治疗缓解率较低,提示CT7可能预示较差的临床预后,但是还需进一步扩大病例数继续研究。
[Abstract]:Background: multiple myeloma is a malignant tumor of the blood system. The incidence of multiple myeloma is about 13% of the malignant tumors of the blood system. It is characterized by abnormal proliferation and infiltration of pathological plasma cells in bone marrow and other hematopoietic tissues, resulting in extensive destruction of bone, anemia, increase of monoclonal globulin or free light chain, impairment of renal function and so on. At present, it is still an incurable disease. To find and identify the important molecular targets and influencing factors in the development of multiple myeloma, and to intervene appropriately to induce apoptosis of tumor cells. Differentiation or regulation of its proliferation, slowing down the development of the disease to achieve therapeutic effect, is still a hot topic. Carcinotesticular antigen 7 cancer testis antigens 7. CT7) is an important member of cancer testis antigens family. It is widely and intensively expressed in plasma cells of patients with multiple myeloma. Objective: to explore the correlation between the expression of CT7 and tumor burden in patients with multiple myeloma. The correlation between clinical stage and clinical stage was used to analyze the different expression of CT7 in bone marrow mononuclear cells of patients with multiple myeloma. To determine the correlation between CT7 and disease prognosis.) to investigate whether the expression of CT7 affects the therapeutic efficacy of multiple myeloma patients. Methods: collect different stages. Bone marrow mononuclear cells (BMC) and bone marrow biopsy specimens from patients with primary and recurrent myeloma were detected for CT7 expression by qPCR and immunohistochemistry respectively, and relevant clinical data were collected. To analyze the correlation between the expression of CT7 and clinical indexes, stages, prognosis, treatment (bortezomie) of myeloma. [results] 80 patients with multiple myeloma were collected in this study. The average age of the patients was 61.01 卤10.887 years old, and the ratio of male to female was 40 / 40% IgG type in 33 patients with IgA type. Among 16 cases of light chain type and 7 cases of other rare types, 111 specimens of myeloma were collected, 43 of which were primary specimens. The expression of CT7 in bone marrow mononuclear cells of patients with multiple myeloma was different at the level of mRNA and protein. The overall positive rate of expression was 72.97% / 111%, of which the positive rate of PCR detection was 79.1% (68 / 86). Immunohistochemical method was used to detect the positive rate of mRNA expression in the bone marrow plasma cells and serum M protein (r = 0.345, r = 0.345, respectively). 0.442p, 0.01g, and 尾 2-microglobulin. There was a significant correlation between the ISS staging and the ratio of bone marrow plasma cells to the protein expression of 0.05. CT7 (P < 0. 03) in the patients with ineffective or relapsed treatment. The positive rate of CT7 protein expression was significantly higher than that of the effective patients (83.3%, 80.0% and 10.0%, 0.002%) in 40 cases of MM followed up. The remission rate in patients with positive CT7 expression was significantly lower than that in patients with negative CT7 expression. There was no significant difference in remission rate between positive and negative CT7 expression patients (84.2 vs 100%). Conclusion: CT7 gene is widely expressed in the bone marrow mononuclear cells of patients with multiple myeloma, and the ratio of CT7 gene to plasma cell is M protein. The expression of 尾 _ 2-microglobulin and other tumor load indexes was significant in the patients with poor therapeutic effect and recurrence, and the remission rate of the patients with positive CT7 expression was lower. The results suggest that CT7 may predict poor clinical prognosis, but further study is needed to further expand the number of cases.
【学位授予单位】：东南大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R733.3

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