Kim Yeong-Jin, Kim Ju-Hwi, Kim Ok, Ahn Eun-Jung, Oh Se-Jeong, Akanda Md Rashedunnabi, Oh In-Jae, Jung Shin, Kim Kyung-Keun, Lee Jae-Hyuk, Kim Hyung-Seok, Kim Hangun, Lee Kyung-Hwa, Moon Kyung-Sub
1Department of Neurosurgery, Chonnam National University Research Institute of Medical Science, Chonnam National University Hwasun Hospital and Medical School, 322 Seoyang-ro, Hwasun-eup, Hwasun-gun, Jeollanam-do 58128 South Korea.
2Department of Pathology, Chonnam National University Research Institute of Medical Science, Chonnam National University Hwasun Hospital and Medical School, 322 Seoyang-ro, Hwasun-eup, Hwasun-gun, Jeollanam-do 58128 South Korea.
Cancer Cell Int. 2019 Jun 28;19:171. doi: 10.1186/s12935-019-0892-0. eCollection 2019.
Caveolin-1 (Cav-1) plays an important role in the development of various human cancers. We investigated the relationship between Cav-1 expression and non-small cell lung cancer (NSCLC) progression in the context of brain metastasis (BM).
Cav-1 expression was investigated in a series of 102 BM samples and 49 paired primary NSCLC samples, as well as 162 unpaired primary NSCLC samples with (63 cases) or without (99 cases) metastasis to distant organs. Human lung cancer cell lines were used for in vitro functional analysis.
High Cav-1 expression in tumor cells was observed in 52% (38/73) of squamous cell carcinomas (SQCs) and 33% (45/138) of non-SQCs. In SQC, high Cav-1 expression was increased after BM in both paired and unpaired samples of lung primary tumors and BM (53% vs. 84% in paired samples, = 0.034; 52% vs. 78% in unpaired samples, = 0.020). Although the difference in median overall survival in patients NSCLC was not statistically significant, high Cav-1 expression in tumor cells (= 0.005, hazard ratio 1.715, 95% confidence index 1.175-2.502) was independent prognostic factors of overall survival on multivariate Cox regression analyses, in addition to the presence of BM and non-SQC type. In vitro assays revealed that Cav-1 knockdown inhibited the invasion and migration of lung cancer cells. Genetic modulation of Cav-1 was consistently associated with SNAIL up- and down-regulation. These findings were supported by increased SNAIL and Cav-1 expression in BM samples of SQC.
Cav-1 plays an important role in the BM of NSCLC, especially in SQC. The mechanism may be linked to SNAIL regulation.
小窝蛋白-1（Cav-1）在多种人类癌症的发展中起重要作用。我们在脑转移（BM）的背景下研究了Cav-1表达与非小细胞肺癌（NSCLC）进展之间的关系。
在一系列102份BM样本和49对配对的原发性NSCLC样本以及162份未配对的原发性NSCLC样本（有远处器官转移63例，无远处器官转移99例）中研究Cav-1表达。用人肺癌细胞系进行体外功能分析。
在52%（38/73）的鳞状细胞癌（SQC）和33%（45/138）的非SQC中观察到肿瘤细胞中Cav-1高表达。在SQC中，配对和未配对的肺原发性肿瘤及BM样本中，BM后Cav-1高表达均增加（配对样本中53%对84%，P=0.034；未配对样本中52%对78%，P=0.020）。虽然NSCLC患者的中位总生存期差异无统计学意义，但在多因素Cox回归分析中，肿瘤细胞中Cav-1高表达（P=0.005，风险比1.715，95%置信区间1.175-2.502）是总生存期的独立预后因素，此外还有BM的存在和非SQC类型。体外实验表明，Cav-1敲低抑制肺癌细胞的侵袭和迁移。Cav-1的基因调控与SNAIL的上调和下调一致相关。这些发现得到SQC的BM样本中SNAIL和Cav-1表达增加的支持。
Cav-1在NSCLC的BM中起重要作用，尤其是在SQC中。其机制可能与SNAIL调控有关。
