抗纺锤体抗体诊断小细胞肺癌的潜在临床价值及其抗肿瘤生物学机制研究

Small cell lung cancer (SCLC) is a kind of undifferentiated carcinoma in lung cancer , with rapid metastasis and low survival. However, no effective and simple method is currently available to screen and monitor this cancer. Our previous data showed mitotic spindle antibody (MSA) exsited in the sera of patients with SCLC; the sensitivity and the specificity of MSA was respectively 43.3% and 97.5%, with significant differences against groups of other tumors and healthy control. Our hypothesis is MSA may serve as a new biomarker for SCLC. In this project, we will detect the levels of MSA in patients with different periods and types of SCLC and establish the clinical value of MSA in diagnosis, treatment and prognosis of SCLC. Besides, we will analyze the role of MSA in cell proliferation and migration. In addition, in tumor model of nude mice, we will identify the monoclonal antibody of MSA playing an anti-tumor role in vivo, find out the according mitotic spindle protein by protein array. Finally, we will illustrate the function of this protein by gene over-expression, silence and stable expression, further with its mechanism using co-immunoprecipitation and mass spectrometry. Together, these studies will be conductive to clarify the effect and mechanism of MSA in tumor biology of SCLC, and may validate MSA as a new biomarker to diagnose and monitor SCLC.

小细胞肺癌(SCLC) 是肺癌中未分化癌的一种，能快速多器官转移，生存率极低。目前临床上缺乏简便、有效的筛查和监测SCLC的方法。我们前期结果显示抗纺锤体抗体对SCLC的诊断敏感性为43.3%，特异性高达97.5%，与对照组有显著差异。目前尚未有纺锤体抗体诊断SCLC的报道。据此我们提出假说：纺锤体抗体具有作为SCLC标志物的潜在临床应用价值。本研究中，我们将进一步明确不同分期及分型的SCLC患者抗纺锤体抗体的含量，评估其在SCLC诊断、治疗及预后的价值；拟从分子，细胞，组织及动物等多层次明确抗纺锤体单克隆抗体对SCLC细胞增殖、凋亡、迁移的影响；鉴定具有抗肿瘤作用的单抗，确定相应的纺锤体蛋白；运用基因过表达、沉默和稳定表达体系研究其生物学功能，并通过免疫共沉淀和质谱分析对机制进行研究。该研究旨在阐明抗纺锤体抗体在SCLC中的抗肿瘤生生物学作用及机制，并为SCLC的诊断和监测提供新思路。

小细胞肺癌(SCLC)是肺癌中未分化癌的一种，能快速多器官转移，生存率极低。细胞分裂异常为SCLC的主要表现形式，纺锤体是细胞分裂前初期到末期的一个特殊的细胞器，抗纺锤体抗体(MSA)即为纺锤体过度增殖而刺激机体免疫功能而产生的自身抗体，与SCLC发生发展密切相关，抗细胞核有丝分裂器蛋白（NuMA）抗体为MSA中最具代表性的蛋白之一。本研究发现MSA并未影响NCI-H446小细胞肺癌细胞的形态和贴壁能力，但对NCI-H446细胞的增殖、迁移和侵袭有显著的抑制作用，且促进其凋亡。在SCLC患者MSA阳性率为37.20%，对SCLC的诊断敏感性为43.3%，特异性高达97.5%。本研究揭示了MSA在SCLC发生发展中的作用机制，为SCLC的诊断、预防及治疗提供了理论及实验依据。