Chen Kaifei, Chen Shuaiqi, Wu Shangrong, Sun Guangyu, Jiang Yuchen, Liu Ranlu
Department of Urology, Tianjin Medical University General Hospital, Tianjin, China.
Transl Cancer Res. 2024 Jun 30;13(6):2825-2846. doi: 10.21037/tcr-23-2148. Epub 2024 Jun 27.
Bladder cancer (BC), as a common type of cancer, has a poor prognosis, also some common invasive prognostic or therapeutic markers are difficult to obtain, which makes further treatment of BC difficult. Glycyl-tRNA synthetase (), as one of the aminoacyl-tRNA synthetases that charge tRNAs with their cognate amino acids, has been identified as a target in many diseases, including tumors.
Bioassay analysis revealed that was in high expression in most cancer tissues. The expression of gene in BC tissues could assess the prognosis of BC patients, and the expression in urinary extracellular vesicles (uEVs) of patients was positively correlated with the expression in tissues. In addition to this, we analyzed -related differential gene expression, copy number variation (CNV) and mutation profiles, potential biological functions, immune cell infiltration and drug sensitivity. and tumorigenic experiments were performed to validate the function of . Single-cell data were used to further analyze its role in the microenvironment.
In our study, we found that was highly expressed in 30 cancer tissues including BC, and high expression was negatively correlated with the prognosis of BC patients. To address this phenomenon, we analyzed the differential genes between high and low groups by enrichment analysis, and identified the biological signaling pathways that were mainly enriched for their functions, and found that the enrichment was found in immune-related signaling pathways and regulation of cell-cell adhesion. Then we found that was positively associated with immune cell infiltration in BC, and some common immune checkpoints were significantly overexpressed in the -high group. Besides, we found that was enriched in myofibroblasts in the tumor microenvironment, and the enrichment was positively correlated with epithelial-mesenchymal transition (EMT)-related genes. This study also showed a positive correlation between and BC RNA stemness. Patients in the -high group had considerably higher rates of and Titin () mutations than those in the -low group. Drug Sensitivity analysis screened for drugs that were more sensitive to -high patients. Further, we found that knockdown of significantly inhibited the proliferation, migration and invasion ability both and . Finally, we found that in patients with high the expression in uEVs was also at a high level.
In summary, this study provided evidence that can be used as a prognostic and therapeutic marker for BC, we can detect in uEVs instead of tissue, to provide a new, simple, noninvasive way to obtain prognostic and therapeutic markers for BC patients.
膀胱癌（BC）作为一种常见的癌症类型，预后较差，且一些常见的侵袭性预后或治疗标志物难以获取，这使得BC的进一步治疗变得困难。甘氨酰 - tRNA合成酶（）作为一种将tRNA与相应氨基酸结合的氨酰 - tRNA合成酶之一，已被确定为包括肿瘤在内的许多疾病的靶点。
生物测定分析显示，在大多数癌症组织中高表达。BC组织中基因的表达可以评估BC患者的预后，患者尿液细胞外囊泡（uEVs）中的表达与组织中的表达呈正相关。除此之外，我们分析了相关的差异基因表达、拷贝数变异（CNV）和突变谱、潜在的生物学功能、免疫细胞浸润和药物敏感性。进行了和肿瘤发生实验以验证的功能。单细胞数据用于进一步分析其在微环境中的作用。
在我们的研究中，我们发现，在包括BC在内的30种癌症组织中高表达，高表达与BC患者的预后呈负相关。为了解决这一现象，我们通过富集分析分析了高组和低组之间的差异基因，并确定了主要因其功能而富集的生物信号通路，发现富集于免疫相关信号通路和细胞间粘附的调节。然后我们发现，在BC中与免疫细胞浸润呈正相关，一些常见的免疫检查点在高组中显著过表达。此外，我们发现，在肿瘤微环境中富集于肌成纤维细胞，且这种富集与上皮 - 间质转化（EMT）相关基因呈正相关。本研究还显示，与BC RNA干性呈正相关。高组患者的和肌联蛋白（）突变率明显高于低组。药物敏感性分析筛选出对高患者更敏感的药物。此外，我们发现敲低显著抑制了和 的增殖、迁移和侵袭能力。最后，我们发现，在高表达的患者中，uEVs中的表达也处于高水平。
总之，本研究提供了证据表明，可作为BC的预后和治疗标志物，我们可以在uEVs中检测而不是在组织中，为BC患者提供一种新的、简单的、非侵入性的获取预后和治疗标志物的方法。
