NOK与p-GSK3β(Tyr216)在非小细胞肺癌中的表达及临床意义
| 作者: |
1黄曌,
1赵晋波,
1卢强,
1张志培,
1赖远阳,
1李维妙,
1张晨曦,
1刘文豪,
1李小飞
1 空军军医大学第二附属医院胸腔外科，西安 710038 |
| 通讯: |
李小飞
Email: lxfchest@fmmu.edu.cn |
| DOI: | 10.3978/j.issn.2095-6959.2019.11.004 |
| 基金: | 国家自然科学基金(81572252)。 |
摘要
目的：检测NOK与p-GSK3β(Tyr216)在非小细胞肺癌(non-small cell lung cancer，NSCLC)中的表达、两者之间的相关性以及蛋白表达和患者预后关系，为研究NOK在肿瘤进展中的作用机制提供依据。方法：采用免疫组织化学法检测NOK与p-GSK3β(Tyr216)在104例NSCLC和10例非肿瘤患者肺组织中的表达，分析组织中表达的差异性和相关性。对患者按蛋白表达情况分组，进行生存分析。结果：肿瘤细胞中NOK阳性着色主要位于细胞质中，p-GSK3β(Tyr216)阳性着色定位于细胞质和细胞核中。NOK蛋白在肿瘤组织中高表达，相对于癌旁组织、非肿瘤肺组织差异均有统计学意义(P<0.001，P<0.05)；p-GSK3β(Tyr216)在正常肺组织、癌旁组织中的相对高表达，而且正常组织与肿瘤组织差异有统计学意义(P<0.001)。NOK的表达与淋巴结转移、TNM分期密切相关(P<0.001)。p-GSK3β(Tyr216)表达与肿瘤组织的病理分类、TNM分期密切相关(P<0.001，P<0.05)。NOK与p-GSK3β(Tyr216)蛋白在NSCLC组织中呈显著负相关(P<0.05，r=−0.264)。NOK高表达、p-GSK3β(Tyr216)低表达患者术后生存时间显著低于两蛋白表达情况相反的患者(P<0.0001)。结论：NOK在高表达和p-GSK3β(Tyr216)低表达与TNM分期密切相关，2个蛋白的表达可能与NSCLC发生发展相关；NOK，p-GSK3β(Tyr216)蛋白在NSCLC组织中呈显著负相关，且2个蛋白可能共同影响NSCLC患者预后。NOK可能与GSK3β相关通路的激活有关。
关键词：
非小细胞肺癌；NOK；p-GSK3β(Tyr216)
Expression and its clinical significance of NOK and p-GSK3β (Tyr216) in non-small cell lung cancer
CorrespondingAuthor: LI Xiaofei Email: lxfchest@fmmu.edu.cn
DOI: 10.3978/j.issn.2095-6959.2019.11.004
Foundation: This work was supported by the National Natural Science Foundation of China (81572252).
Abstract
Objective: To investigate the expressions of NOK and p-GSK3β (Tyr216) in non-small cell lung cancer (NSCLC). Methods: The expression rates of NOK and p-GSK3β (Tyr216) proteins in 104 patients with NSCLC and 10 patients without NSCLC was detected by immunohistochemical stain. The clinical correlations between two proteins were analyzed by statistics. Survival analysis was performed on grouping patients according to proteins expression. Results: The NOK positive expression was mainly located in cytoplasm and p-GSK3β (Tyr216) was mainly located in the cytoplasm and nucleus. NOK protein was highly expressed in tumor tissues, which was significantly different from the expression in corresponding adjacent tissues and non-tumor lung tissues (P<0.001, P<0.05). The expression of p-GSK3β (Tyr216) was higher relatively in normal lung tissues and adjacent tissues than that in tumor tissues. And the difference between normal tissue and tumor tissue was significant (P<0.001). There were significant differences for NOK expression among lymphatic invasion and TNM stages in NSCLC (P<0.001). There were significant differences for p-GSK3β (Tyr216) expression among pathology type and TNM stages in NSCLC (P<0.001, P<0.05). There was significantly negative correlation between positive and intensity of NOK and p-GSK3β (Tyr216) expression in NSCLC tissues (r=−0.264, P<0.05). The survival time of patients with high expression of NOK and low expression of p-GSK3β (Tyr216) was significantly lower than that of patients with opposite expression of two proteins (P<0.0001). Conclusion: The NOK proteins are highly expressed and the p-GSK3β (Tyr216) proteins are lowly expressed in the NSCLC, which is correlated with TNM stages. The expressions of NOK and p-GSK3β (Tyr216) proteins may be connected with tumor genesis and progression. NOK and p-GSK3β (Tyr216) proteins have a significantly negative correlation in NSCLC tissues, which may work together to influence the prognosis of NSCLC patients. It reveals that NOK may be involved in the activation of GSK3β-related pathways, which provides a clue for further study on the role and mechanism of NOK in NSCLC.
Keywords：
non-small cell lung cancer; NOK; p-GSK3β (Tyr216)