肿瘤睾丸抗原POTE调控凋亡信号参与NSCLC发生的机制研究

Cancer-testis antigens (CTA) are considered as promising targets of tumor immunotherapy owing to their biased expression pattern and their immunogenicity in cancer patients. POTE is a new class of CTA and its functions is still unclear. In our previous study, we found POTEE was the main subtype of POTE in lung adenocarcinoma cells, and may regulate apoptosis signal pathway. We also found POTEE has expressed in 62.5% of lung cancer patients sera samples, but not expressed in control samples. In addition, the POTEE mRNA expression level may be associated with the prognosis of advanced NSCLC patients. Therefore, we speculate POTE may involve in development of non-small cell lung cancer, and maybe a candidate target of lung cancer immunotherapy. On the basis of the preliminary results, we intend to investigate the role and related mechanisms of POTE in proliferation and apoptosis of lung cancer by gene clone, siRNA, western-blot, apoptosis assay, ELISA, IHC and other lab works. In addition, the potentiality of POTE as a candidate target will be analyzed in lung cancer immunotherapy.

肿瘤睾丸抗原（cancer-testis antigen，CTA）因其独特的表达模式和诱发免疫应答的潜能，一直是肿瘤免疫治疗的潜在候选靶点。POTE是新发现的一类CTA，其生物学功能及在肿瘤中的作用尚未阐明。我们前期研究发现肺腺癌细胞POTE的主要亚型是POTEE，与凋亡信号调节相关；62.5%的肺癌患者血清中存在POTEE表达，而对照组中不表达POTEE。另外，我们检测了81例晚期非小细胞肺癌患者的肿瘤组织样本，发现POTEE的mRNA表达水平可能与预后相关。因此，我们推测POTE可能参与了非小细胞肺癌的发生发展，并有可能成为肺癌免疫治疗的候选靶点。本课题在前期研究的基础上，拟采用基因克隆、siRNA、western-blot、凋亡检测、ELISA、IHC等方法从细胞、动物和临床样本三个层面探讨POTE在肺癌增殖和凋亡中的作用和相关机制，并初探其作为肺癌免疫治疗候选靶点的可能性。

POTE作为一种肿瘤睾丸抗原（cancer-testis antigen，CTA），只在肿瘤细胞表达，其在肿瘤中的生物学功能及作用尚未阐明。该项目旨在探讨POTE在肺癌中的功能和作用。通过临床样本分析、细胞学等实验课题组发现：1、62.5%的肺癌患者血清中存在POTEE表达，而对照组中不表达POTEE，血清中POTEE低水平表达较高表达患者预后更好；2、与血清POTEE的临床意义不同，肿瘤组织POTEE mRNA高表达患者预后更好；3、通过上调和下调POTEE表达，发现上调POTEE表达后细胞株的增殖能力、迁移和侵袭能力降低，而凋亡能力增强，促凋亡蛋白BIM、BAK、BAX、FAS等表达上调而抗凋亡蛋白BCL2则表达降低；下调POTEE表达后细胞株的增殖能力、迁移和侵袭能力增强，而凋亡能力减弱。4、上调POTEE表达后EGFR/PI3K/AKT和ERK/MAPK信号通路活性明显降低，下调POTEE表达后，上述信号通络明显活化。以上结果我们推断POTEE主要通过调节凋亡途径以及EGFR/PI3K/AKT和ERK/MAPK信号通络参与NSCLC的发生和发展.