Miwa Nanako, Nagano Tatsuya, Jimbo Naoe, Dokuni Ryota, Kiriu Tatsunori, Mimura Chihiro, Yasuda Yuichiro, Katsurada Masahiro, Yamamoto Masatsugu, Tachihara Motoko, Tanaka Yugo, Kobayashi Kazuyuki, Itoh Tomoo, Maniwa Yoshimasa, Nishimura Yoshihiro
Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Japan.
Onco Targets Ther. 2020 Sep 10;13:9005-9013. doi: 10.2147/OTT.S265539. eCollection 2020.
Caspase recruitment domain-containing protein 9 (CARD9) is expressed at high levels in bone marrow cells and has a crucial role in innate immunity. Current studies indicate that CARD9 also plays a key role in tumor progression, but there are few reports on the role of CARD9 in lung cancer. The aim of this study was to clarify the role of CARD9 in lung adenocarcinoma.
Lung adenocarcinoma tumor samples from 74 patients who underwent complete resection at Kobe University Hospital from January 2014 to December 2014 were analyzed by immunohistochemistry. The role of CARD9 in cancer cells was analyzed using lung cancer cell lines treated with CARD9 siRNA.
High expression of CARD9 was observed in 32.4% of tumors, and compared to low expression of CARD9, high expression was associated with poorer overall survival (P = 0.0365). Univariate and multivariate analyses showed that high expression of CARD9 was an independent prognostic factor. Knockdown of CARD9 in lung adenocarcinoma cells inhibited proliferation but did not increase apoptosis. In addition, CARD9 activated the NF-κB pathway in a lung adenocarcinoma cell line.
CARD9 was shown to be an independent prognostic factor of poor outcome for lung cancer and may represent a molecular target for treatment.
含半胱天冬酶招募结构域蛋白9（CARD9）在骨髓细胞中高表达，在固有免疫中起关键作用。目前的研究表明，CARD9在肿瘤进展中也起关键作用，但关于CARD9在肺癌中的作用报道较少。本研究旨在阐明CARD9在肺腺癌中的作用。
对2014年1月至2014年12月在神户大学医院接受根治性切除的74例肺腺癌肿瘤样本进行免疫组化分析。使用经CARD9小干扰RNA（siRNA）处理的肺癌细胞系分析CARD9在癌细胞中的作用。
32.4%的肿瘤中观察到CARD9高表达，与CARD9低表达相比，高表达与较差的总生存期相关（P = 0.0365）。单因素和多因素分析表明，CARD9高表达是一个独立的预后因素。肺腺癌细胞中CARD9基因敲低抑制增殖但不增加凋亡。此外，CARD9在一个肺腺癌细胞系中激活核因子κB（NF-κB）通路。
CARD9被证明是肺癌预后不良的一个独立预后因素，可能是治疗的分子靶点。
