Abstract：
Carbonic anhydrase 4 (CA4) is a member of a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide and was found to have low expression in non-small cell lung cancer (NSCLC). However, the specific role of CA4 in NSCLC and the underlying mechanisms remain unknown.
The bioinformatic analysis on lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) datasets downloaded from The Cancer Genome Atlas (TCGA) database was performed. We found that CA4 expression was lower in tumors than that in normal tissues, which were verified by Real-time PCR. Lower CA4 levels were significantly associated with higher T stages in LUAD and LUSC cohorts. Multivariate analysis showed that CA4 is an independent prognostic factor for NSCLC. Furthermore, the expression of CA4 also correlated with immune infiltration and drug sensitivity.
Ectopic expression of CA4 decreased NSCLC cell proliferation in vitro by CCK-8 assay. CA4 caused G0/G1 cell cycle arrest by cell experiments. Mechanistic studies found that CA affects the cell cycle and inhibits cell proliferation by downregulating the expression of CDK2.
The present findings highlight the role of CA4 in NSCLC and identify CA4 as a potential novel diagnostic and prognostic biomarker for the treatment of NSCLC.
The bioinformatic analysis on lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) datasets downloaded from The Cancer Genome Atlas (TCGA) database was performed. We found that CA4 expression was lower in tumors than that in normal tissues, which were verified by Real-time PCR. Lower CA4 levels were significantly associated with higher T stages in LUAD and LUSC cohorts. Multivariate analysis showed that CA4 is an independent prognostic factor for NSCLC. Furthermore, the expression of CA4 also correlated with immune infiltration and drug sensitivity.
Ectopic expression of CA4 decreased NSCLC cell proliferation in vitro by CCK-8 assay. CA4 caused G0/G1 cell cycle arrest by cell experiments. Mechanistic studies found that CA affects the cell cycle and inhibits cell proliferation by downregulating the expression of CDK2.
The present findings highlight the role of CA4 in NSCLC and identify CA4 as a potential novel diagnostic and prognostic biomarker for the treatment of NSCLC.
摘要：
背景技术碳酸酐酶4(CA4)是催化二氧化碳可逆水合的锌金属酶大家族的成员,并且被发现在非小细胞肺癌(NSCLC)中具有低表达。然而,CA4在NSCLC中的具体作用和潜在机制尚不清楚.方法对从癌症基因组图谱(TCGA)数据库下载的肺腺癌(LUAD)和肺鳞癌(LUSC)数据集进行生物信息学分析。我们发现CA4在肿瘤中的表达低于正常组织,通过实时PCR验证。在LUAD和LUSC队列中，较低的CA4水平与较高的T分期显着相关。多因素分析显示CA4是NSCLC的独立预后因素。此外，CA4的表达也与免疫浸润和药物敏感性有关。结果：CCK-8法检测CA4的异位表达可降低NSCLC细胞的体外增殖。通过细胞实验,CA4引起G0/G1细胞周期阻滞。机制研究发现CA通过下调CDK2的表达影响细胞周期并抑制细胞增殖。结论本研究结果强调了CA4在NSCLC中的作用，并确定CA4是治疗NSCLC的潜在新型诊断和预后生物标志物。
