Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Oncology, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.
Front Immunol. 2022 Jan 27;13:803355. doi: 10.3389/fimmu.2022.803355. eCollection 2022.
Bladder cancer (BLCA) is a common malignant tumor of the urinary tract, which is the sixth most common cancer among men. Numerous studies suggested that pyroptosis and long noncoding RNAs (lncRNAs) played an essential role in the development of cancers. However, the role of pyroptosis-related lncRNAs in BLCA and their prognostic value are still unclear.
In this study, we constructed a signature model through least absolute shrinkage and selection operator (LASSO) Cox regression analysis and Cox univariate analysis based on The Cancer Genome Atlas (TCGA) database. The expression of 12 pyroptosis-related lncRNAs was also confirmed by qRT-PCR in BLCA cell lines. TIMER, XCELL, QUANTISEQ, MCPCOUNTER, EPIC, and CIBERSORT R script were applied to quantify the relative proportions of infiltrating immune cells. Correlation coefficients were computed by Spearman analyses. The Kaplan-Meier method, Cox regression model, and log-rank tests were used to evaluate the prognostic value. The R package of pRRophetic was used to predict IC50 of common chemotherapeutic agents.
A total of 12 pyroptosis-related lncRNAs with great prognosis value were identified. The expression was investigated by qRT-PCR in four BLCA cell lines. Then, 126 cases were identified as high-risk group, and 277 cases were identified as low-risk group based on the cutoff point. Patients in the low-risk group showed a significant survival advantage. Furthermore, we found that clinical features were significantly related to the risk score. As well, based on the C-index values, a nomogram was constructed. The gene set enrichment analysis (GSEA) results showed that mitogen-activated protein kinase (MAPK) signaling, transforming growth factor (TGF)-β signaling, and WNT signaling were with important significance in the high-risk group. Moreover, we found that riskscore was positively correlated with M0 macrophages and M2 macrophages.
In conclusion, our study indicated that pyroptosis is closely connected to BLCA. The riskscore generated from the expression of 12 pyroptosis-related lncRNAs was evaluated by various clinical features including survival status, tumor microenvironment, clinicopathological characteristic, and chemotherapy. It may offer a significant basis for future studies.
膀胱癌（BLCA）是一种常见的泌尿道恶性肿瘤，是男性中第六大常见癌症。大量研究表明，细胞焦亡和长链非编码 RNA（lncRNA）在癌症的发展中起着重要作用。然而，细胞焦亡相关 lncRNA 在 BLCA 中的作用及其预后价值尚不清楚。
本研究基于癌症基因组图谱（TCGA）数据库，通过最小绝对值收缩和选择算子（LASSO）Cox 回归分析和 Cox 单因素分析构建了一个签名模型。还通过 qRT-PCR 在 BLCA 细胞系中验证了 12 个细胞焦亡相关 lncRNA 的表达。采用 TIMER、XCELL、QUANTISEQ、MCPCOUNTER、EPIC 和 CIBERSORT R 脚本量化浸润免疫细胞的相对比例。采用 Spearman 分析计算相关系数。采用 Kaplan-Meier 法、Cox 回归模型和对数秩检验评估预后价值。采用 pRRophetic R 包预测常用化疗药物的 IC50。
共鉴定出 12 个具有良好预后价值的细胞焦亡相关 lncRNA。通过 qRT-PCR 在 4 个 BLCA 细胞系中进行了检测。然后，根据截断值，将 126 例患者鉴定为高危组，将 277 例患者鉴定为低危组。低危组患者的生存优势显著。此外，我们发现临床特征与风险评分显著相关。同样，基于 C 指数值构建了一个列线图。基因集富集分析（GSEA）结果表明，高危组中丝裂原活化蛋白激酶（MAPK）信号、转化生长因子（TGF）-β信号和 WNT 信号具有重要意义。此外，我们发现风险评分与 M0 巨噬细胞和 M2 巨噬细胞呈正相关。
综上所述，本研究表明细胞焦亡与 BLCA 密切相关。通过 12 个细胞焦亡相关 lncRNA 的表达评估生成的风险评分与包括生存状态、肿瘤微环境、临床病理特征和化疗在内的各种临床特征相关。它可能为未来的研究提供重要的基础。
