Wu Yucai, Xu Yangyang, He Shiming, Li Yifan, Feng Ninghan, Fan Jian, Gong Yanqing, Li Xuesong, Zhou Liqun
Department of Urology, Peking University First Hospital, Beijing, China.
Institute of Urology, Peking University, Beijing, China.
Heliyon. 2023 Feb 13;9(3):e13707. doi: 10.1016/j.heliyon.2023.e13707. eCollection 2023 Mar.
Dysregulation of long noncoding RNAs (lncRNAs) has been reported to be associated with multiple tumors where they act as tumor suppressors or accelerators. The lncRNA was identified as an oncogene involved in many cancers, such as gastric cancer, colorectal cancer, hepatocellular carcinoma, and renal cell carcinoma. However, the role of in bladder cancer (BCa) has rarely been reported.
Using cancer datasets from The Cancer Genome Atlas (TCGA) program, we analyzed the association between expression and prognostic value, oncogenic pathways, antitumor immunity and immunotherapy response in BCa. The influence of on the immune infiltration pattern in the urothelial carcinoma microenvironment was further verified in our dataset. Single-cell analysis revealed the role of in the tumor microenvironment (TME) of BCa. Finally, we evaluated the expression of in BCa in the Peking University First Hospital (PKU-BCa) dataset and its correlation with the malignant phenotype of BCa and .
The results indicated that was highly expressed in multiple cancer samples, including BCa, and increased expression contributed to poor overall survival (OS). Additionally, elevated expression was significantly correlated with clinicopathological features of BCa, such as female sex, advanced TNM stage, high histological grade and non-papillary subtype. Functional characterization revealed that may be involved in immune-related pathways and the epithelial mesenchymal transformation (EMT) process. Moreover, had a significant association with infiltrating immune cells, including M2 macrophages and regulatory T cells (Tregs). facilitates the crosstalk between cancer-associated fibroblasts (CAFs) and macrophages, and mediates M2 polarization of macrophages. Correlation analysis revealed a positive correlation between expression and programmed cell death-1 ()/programmed death ligand 1 ()/expression and other targets for specific immunotherapy in BCa, which are recognized to predict the efficacy of immunotherapy.
These results suggest that serves as a potential biomarker for predicting survival outcome, TME cell infiltration characteristics and immunotherapy response in BCa.
据报道，长链非编码RNA（lncRNA）失调与多种肿瘤相关，在这些肿瘤中它们可作为肿瘤抑制因子或促进因子。lncRNA被鉴定为一种致癌基因，参与许多癌症，如胃癌、结直肠癌、肝细胞癌和肾细胞癌。然而，其在膀胱癌（BCa）中的作用鲜有报道。
利用来自癌症基因组图谱（TCGA）项目的癌症数据集，我们分析了BCa中lncRNA表达与预后价值、致癌途径、抗肿瘤免疫和免疫治疗反应之间的关联。在我们的数据集中进一步验证了lncRNA对尿路上皮癌微环境中免疫浸润模式的影响。单细胞分析揭示了lncRNA在BCa肿瘤微环境（TME）中的作用。最后，我们评估了北京大学第一医院（PKU-BCa）数据集中BCa中lncRNA的表达及其与BCa恶性表型和的相关性。
结果表明，lncRNA在包括BCa在内的多种癌症样本中高表达，lncRNA表达增加导致总体生存期（OS）较差。此外，lncRNA表达升高与BCa的临床病理特征显著相关，如女性、晚期TNM分期、高组织学分级和非乳头状亚型。功能特征表明，lncRNA可能参与免疫相关途径和上皮-间质转化（EMT）过程。此外，lncRNA与浸润性免疫细胞，包括M2巨噬细胞和调节性T细胞（Tregs）有显著关联。lncRNA促进癌症相关成纤维细胞（CAFs）与巨噬细胞之间的相互作用，并介导巨噬细胞的M2极化。相关性分析显示，BCa中lncRNA表达与程序性细胞死亡蛋白1（PD-1）/程序性死亡配体1（PD-L1）表达及其他特定免疫治疗靶点之间呈正相关，这些靶点被认为可预测免疫治疗疗效。
这些结果表明，lncRNA可作为预测BCa生存结局、TME细胞浸润特征和免疫治疗反应的潜在生物标志物。
