PDF(Pubmed)
Abstract：
UNASSIGNED: 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 (GARS), 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.
UNASSIGNED: Bioassay analysis revealed that GARS was in high expression in most cancer tissues. The expression of GARS 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 GARS-related differential gene expression, copy number variation (CNV) and mutation profiles, potential biological functions, immune cell infiltration and drug sensitivity. In vivo and vitro tumorigenic experiments were performed to validate the function of GARS. Single-cell data were used to further analyze its role in the microenvironment.
UNASSIGNED: In our study, we found that GARS was highly expressed in 30 cancer tissues including BC, and high GARS expression was negatively correlated with the prognosis of BC patients. To address this phenomenon, we analyzed the differential genes between high and low GARS 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 GARS was positively associated with immune cell infiltration in BC, and some common immune checkpoints were significantly overexpressed in the GARS-high group. Besides, we found that GARS 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 GARS and BC RNA stemness. Patients in the GARS-high group had considerably higher rates of P53 and Titin (TTN) mutations than those in the GARS-low group. Drug Sensitivity analysis screened for drugs that were more sensitive to GARS-high patients. Further, we found that knockdown of GARS significantly inhibited the proliferation, migration and invasion ability both in vivo and in vitro. Finally, we found that in patients with high GARS the expression in uEVs was also at a high level.
UNASSIGNED: In summary, this study provided evidence that GARS can be used as a prognostic and therapeutic marker for BC, we can detect GARS in uEVs instead of tissue, to provide a new, simple, noninvasive way to obtain prognostic and therapeutic markers for BC patients.
UNASSIGNED: Bioassay analysis revealed that GARS was in high expression in most cancer tissues. The expression of GARS 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 GARS-related differential gene expression, copy number variation (CNV) and mutation profiles, potential biological functions, immune cell infiltration and drug sensitivity. In vivo and vitro tumorigenic experiments were performed to validate the function of GARS. Single-cell data were used to further analyze its role in the microenvironment.
UNASSIGNED: In our study, we found that GARS was highly expressed in 30 cancer tissues including BC, and high GARS expression was negatively correlated with the prognosis of BC patients. To address this phenomenon, we analyzed the differential genes between high and low GARS 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 GARS was positively associated with immune cell infiltration in BC, and some common immune checkpoints were significantly overexpressed in the GARS-high group. Besides, we found that GARS 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 GARS and BC RNA stemness. Patients in the GARS-high group had considerably higher rates of P53 and Titin (TTN) mutations than those in the GARS-low group. Drug Sensitivity analysis screened for drugs that were more sensitive to GARS-high patients. Further, we found that knockdown of GARS significantly inhibited the proliferation, migration and invasion ability both in vivo and in vitro. Finally, we found that in patients with high GARS the expression in uEVs was also at a high level.
UNASSIGNED: In summary, this study provided evidence that GARS can be used as a prognostic and therapeutic marker for BC, we can detect GARS in uEVs instead of tissue, to provide a new, simple, noninvasive way to obtain prognostic and therapeutic markers for BC patients.
摘要：
■膀胱癌（BC），作为一种常见的癌症，预后不良,一些常见的侵入性预后或治疗标志物也很难获得，这使得BC的进一步治疗变得困难。甘氨酰-tRNA合成酶（GARS），作为一种氨基酰基-tRNA合成酶，将tRNA与它们的同源氨基酸一起充电，已被确定为许多疾病的目标，包括肿瘤.
■生物测定分析显示GARS在大多数癌组织中高表达。GARS基因在BC组织中的表达可以评估BC患者的预后，患者尿细胞外囊泡（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GARS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。进行体内和体外致瘤实验以验证GARS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GARS在包括BC在内的30个癌症组织中高表达，GARS的高表达与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和低GARS组之间的差异基因，并确定了主要富集其功能的生物信号通路，并发现在免疫相关的信号通路和细胞间粘附的调节中发现了富集。然后我们发现GARS与BC的免疫细胞浸润呈正相关，一些常见的免疫检查点在GARS-high组中显著过表达。此外,我们发现GARS在肿瘤微环境中富含肌成纤维细胞，富集与上皮间质转化（EMT）相关基因呈正相关。本研究还显示GARS与BCRNA干性之间呈正相关。GARS高组患者的P53和Titin（TTN）突变率明显高于GARS低组。药物敏感性分析筛选了对高GARS患者更敏感的药物。Further,我们发现敲除GARS显著抑制了增殖，体内和体外的迁移和侵袭能力。最后,我们发现，在高GARS患者中，uEV的表达也处于高水平。
■总之，这项研究提供了证据，证明GARS可以用作BC的预后和治疗标志物，我们可以在uEV而不是组织中检测GARS，提供一个新的,简单,获得BC患者预后和治疗标志物的非侵入性方法。
■生物测定分析显示GARS在大多数癌组织中高表达。GARS基因在BC组织中的表达可以评估BC患者的预后，患者尿细胞外囊泡（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GARS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。进行体内和体外致瘤实验以验证GARS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GARS在包括BC在内的30个癌症组织中高表达，GARS的高表达与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和低GARS组之间的差异基因，并确定了主要富集其功能的生物信号通路，并发现在免疫相关的信号通路和细胞间粘附的调节中发现了富集。然后我们发现GARS与BC的免疫细胞浸润呈正相关，一些常见的免疫检查点在GARS-high组中显著过表达。此外,我们发现GARS在肿瘤微环境中富含肌成纤维细胞，富集与上皮间质转化（EMT）相关基因呈正相关。本研究还显示GARS与BCRNA干性之间呈正相关。GARS高组患者的P53和Titin（TTN）突变率明显高于GARS低组。药物敏感性分析筛选了对高GARS患者更敏感的药物。Further,我们发现敲除GARS显著抑制了增殖，体内和体外的迁移和侵袭能力。最后,我们发现，在高GARS患者中，uEV的表达也处于高水平。
■总之，这项研究提供了证据，证明GARS可以用作BC的预后和治疗标志物，我们可以在uEV而不是组织中检测GARS，提供一个新的,简单,获得BC患者预后和治疗标志物的非侵入性方法。
