Ma Teng, Gu Jie, Wen Haoyu, Xu Fengkai, Ge Di
Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
J Cancer. 2022 Aug 21;13(10):3140-3150. doi: 10.7150/jca.69236. eCollection 2022.
Lung adenocarcinoma (LUAD) is the most prevalent thoracic cancer with the highest incidence and mortality worldwide. Baculoviral IAP Repeat Containing 5 (BIRC5) is well studied in many malignancies, its prognosis value and correlation with the tumor microenvironment (TME) in LAUD remains largely elusive. The Wilcoxon signed-rank test and logistic regression were used to evaluate the relationship between clinical features and BIRC5 expression in LUAD. To assess the impact of BIRC5 on prognosis, the Kaplan-Meier plotter analysis and Cox regression were used, as well as a receiver operating characteristic (ROC) curve and nomogram. Gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) were recruited to predict the association between BIRC5 and immune cell infiltrations. Furthermore, qRT-PCR and western bolt were utilized to confirm gene expression on mRNA and protein levels. The proliferation of A549 and H1299 cells was evaluated using CCK8 and EdU assay. Cell mobility was tested by transwell assay and wound healing assay. Detection of PD-L1 and infiltrated CD8 T cells in xenograft tumors was done by flow cytometry. BIRC5 expression was found to be substantially greater in LUAD patients. According to KM-plotter analysis, patients with high levels of BIRC5 had shorter survival rates. Multivariate Cox analysis revealed that elevated BIRC5 expression was an independent risk factor for OS and PFS in LUAD patients. High BIRC5 expression was predicted to be associated with chemokine activity and immune cell chemotaxis, whereas ssGSEA suggested that BIRC5 is highly associated with CD8 T cell infiltration and PD-L1 levels. experiments suggested overexpression of BIRC5 promoted the proliferation, mobility, and PD-L1 level of A549 cells, and vice versa in H1299 cells. Furthermore, study suggested elevated tumor weight and PD-L1 levels in xenograft tumors generated from LLC cells with overexpressed BIRC5. BIRC5 promotes lung adenocarcinoma progression by modulating PD-L1 expression and inducing tumor immune evasion.
肺腺癌（LUAD）是全球发病率和死亡率最高的最常见的胸段癌症。杆状病毒IAP重复序列包含蛋白5（BIRC5）在许多恶性肿瘤中都有深入研究，但其在LUAD中的预后价值以及与肿瘤微环境（TME）的相关性仍 largely难以捉摸。采用Wilcoxon符号秩检验和逻辑回归来评估LUAD临床特征与BIRC5表达之间的关系。为评估BIRC5对预后的影响，使用了Kaplan-Meier绘图仪分析和Cox回归，以及受试者工作特征（ROC）曲线和列线图。采用基因集富集分析（GSEA）和单样本基因集富集分析（ssGSEA）来预测BIRC5与免疫细胞浸润之间的关联。此外，利用qRT-PCR和蛋白质免疫印迹法在mRNA和蛋白质水平上确认基因表达。使用CCK8和EdU检测法评估A549和H1299细胞的增殖。通过Transwell检测法和伤口愈合检测法测试细胞迁移能力。通过流式细胞术检测异种移植肿瘤中的PD-L1和浸润的CD8 T细胞。发现LUAD患者中BIRC5表达明显更高得多。根据KM绘图仪分析，BIRC5水平高的患者生存率较短。多变量Cox分析显示，BIRC5表达升高是LUAD患者总生存期（OS）和无进展生存期（PFS）的独立危险因素。预测高BIRC5表达与趋化因子活性和免疫细胞趋化性相关，而ssGSEA表明BIRC5与CD8 T细胞浸润和PD-L1水平高度相关。实验表明，BIRC5过表达促进了A549细胞的增殖、迁移能力和PD-L1水平，而在H1299细胞中则相反。此外，研究表明，在过表达BIRC5的LLC细胞产生的异种移植肿瘤中，肿瘤重量和PD-L1水平升高。BIRC5通过调节PD-L1表达和诱导肿瘤免疫逃逸促进肺腺癌进展。
