Wang Yiru, Zhang Shijie, Bai Yang, Li Gen, Wang Siyu, Chen Jiayi, Liu Xin, Yin Hang
Department of Gynecologic Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
Department of Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
Front Cell Dev Biol. 2022 Mar 2;10:809747. doi: 10.3389/fcell.2022.809747. eCollection 2022.
Bladder cancer (BC) is a highly prevalent cancer form of the genitourinary system; however, the effective biomarkers are still ambiguous and deserve deeper investigation. Long non-coding RNA (lncRNA) occupies a prominent position in tumor biology and immunology, and ferroptosis-related genes participate in regulatory processes of cancer. In this study, 538 differentially expressed ferroptosis-related lncRNAs were identified from the The Cancer Genome Atlas database through co-expression method and differential expression analysis. Then, the samples involved were equally and randomly divided into two cohorts for the construction of gene model and accuracy verification. Subsequently, a prediction model containing five ferroptosis-related lncRNAs was constructed by LASSO and Cox regression analysis. Furthermore, in terms of predictive performance, consistent results were achieved in the training set, testing set, and entire set. Kaplan-Meier curve, receiver operating characteristic area under the curve, and principal component analysis results verified the good predictive ability of model, and the gene model was confirmed as an independent prognostic indicator. To further investigate the mechanism, we explored the upstream of five lncRNAs and found that they may be modified by m6A to increase or decrease their expression in BC. Importantly, the low-risk group displayed higher mutation burden of tumors and lower Tumor Immune Dysfunction and Exclusion score, which may be predicted to have a higher response rate to immunotherapy. Interestingly, the patients in the high-risk group appeared to have a higher sensitivity to traditional chemotherapeutic agents through pRRophetic analysis. In general, our research established a five-ferroptosis-related lncRNA signature, which can be served as a promising prognostic biomarker for BC.
膀胱癌（BC）是泌尿生殖系统中一种高度常见的癌症形式；然而，有效的生物标志物仍不明确，值得深入研究。长链非编码RNA（lncRNA）在肿瘤生物学和免疫学中占据重要地位，且铁死亡相关基因参与癌症的调控过程。在本研究中，通过共表达方法和差异表达分析，从癌症基因组图谱数据库中鉴定出538个差异表达的铁死亡相关lncRNA。然后，将所涉及的样本平均随机分为两个队列，用于构建基因模型和准确性验证。随后，通过LASSO和Cox回归分析构建了一个包含5个铁死亡相关lncRNA的预测模型。此外，在预测性能方面，训练集、测试集和整个数据集均取得了一致的结果。Kaplan-Meier曲线、受试者工作特征曲线下面积和主成分分析结果验证了该模型具有良好的预测能力，且该基因模型被确认为独立的预后指标。为进一步探究其机制，我们探索了5个lncRNA的上游，发现它们可能被m6A修饰，从而在膀胱癌中上调或下调其表达。重要的是，低风险组显示出更高的肿瘤突变负担和更低的肿瘤免疫功能障碍与排除评分，这可能预示着对免疫治疗有更高的反应率。有趣的是，通过pRRophetic分析，高风险组的患者似乎对传统化疗药物具有更高的敏感性。总体而言，我们的研究建立了一个与铁死亡相关的5lncRNA特征，可作为膀胱癌一个有前景的预后生物标志物。
