Zhang Yundi, Lu Xuan, Zhang Yueyang, Zhao Dongbo, Gong Haoming, Du Yuxin, Sun Hua
National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
School of Life Sciences, Hefei Normal University, Hefei, China.
Front Oncol. 2022 Mar 8;12:722646. doi: 10.3389/fonc.2022.722646. eCollection 2022.
The recognition of new diagnostic and prognostic biological markers for lung cancer, the most severe malignant tumor, is an essential and eager study. In a microenvironment, superoxide dismutase 3 (SOD3) can adjust active oxygen, and it refers to a secreted antioxidant enzyme. It was also found to be cancer-related, and in lung cancer, it was remarkably down-regulated. More and more new cancer research focuses on the function of SOD3. Despite this, there is no good description of SOD3 function in the LC progression.
Through bioinformatics analysis, we found that SOD3 was a possible novel lung cancer gene in this study. We analyzed data sets from Gene Expression Comprehensive Database (GEO) and the Cancer Genome Atlas (TCGA), and SOD3 expression was studied in lung cancer. This study estimated the SOD3 diagnosis and prognosis through gene expression differential display, gene set enrichment analysis (GSEA), enrichment and genomes (KEGG) analysis, and gene ontology (GO). Then in order to investigate the SOD3 presentation in lung cancer cells, we used Western Blot and also applied Flow cytometry to detect the impact of anti-tumor medicine on tumor cell apoptosis.
We found that the expression level of SOD3 in lung cancer was low (P = 4.218E-29), while the survival of lung cancer patients with high SOD3 expression was shorter (LUSC p =0.00086, LUAD p=0.00038). According to the result of western blot, the expression of SOD3 in tumor cells was higher than that in normal cells. The ratio of early apoptosis induced by anti-cancer drugs was 10.5% in normal cells, 35.1% in squamous cell carcinoma and 36.9% in adenocarcinoma.The SOD3 high expression was associated with poor survival probability by multivariate analysis (HR: 1.006, 95% CI 1.002-1.011, p=0.006). Moreover, SOD3 high expression group had higher ESTIMATE scores, and larger amount of immune infiltrating cells. SOD3 expression is correlated with PDCD1 and CTLA4 expression.
SOD3 gene can be used as a prognostic gene in lung cancer patients, and lung cancer patients with high expression of this gene can reap worse prognostic outcome. It can be used as a new clinical method and prognosticator for lung cancer patients.
肺癌是最严重的恶性肿瘤，识别其新的诊断和预后生物学标志物是一项重要且迫切的研究。在微环境中，超氧化物歧化酶3（SOD3）可调节活性氧，它是一种分泌型抗氧化酶。还发现其与癌症相关，在肺癌中显著下调。越来越多的癌症新研究聚焦于SOD3的功能。尽管如此，目前尚无关于SOD3在肺癌进展中功能的详尽描述。
通过生物信息学分析，我们发现SOD3在本研究中是一个可能的新型肺癌基因。我们分析了来自基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）的数据集，并研究了肺癌中SOD3的表达情况。本研究通过基因表达差异显示、基因集富集分析（GSEA）、富集和基因组（KEGG）分析以及基因本体（GO）来评估SOD3的诊断和预后。然后，为了研究SOD3在肺癌细胞中的表现，我们使用了蛋白质免疫印迹法，并应用流式细胞术检测抗肿瘤药物对肿瘤细胞凋亡的影响。
我们发现肺癌中SOD3的表达水平较低（P = 4.218E - 29），而SOD3高表达的肺癌患者生存期较短（肺鳞癌p = 0.00086，肺腺癌p = 0.00038）。根据蛋白质免疫印迹结果，肿瘤细胞中SOD3的表达高于正常细胞。抗癌药物诱导的正常细胞早期凋亡率为10.5%，鳞状细胞癌为35.1%，腺癌为36.9%。多因素分析显示SOD3高表达与较差的生存概率相关（HR：1.006，95% CI 1.002 - 1.011，p = 0.006）。此外，SOD3高表达组具有更高的ESTIMATE评分和更多的免疫浸润细胞。SOD3表达与程序性死亡蛋白1（PDCD1）和细胞毒性T淋巴细胞相关抗原4（CTLA4）表达相关。
SOD3基因可作为肺癌患者的预后基因，该基因高表达的肺癌患者预后较差。它可作为肺癌患者新的临床方法和预后指标。
