Abstract：
BACKGROUND: Vesicular transport (VT) has a complex relationship with tumor progression and immunity. But prognostic significance of VT in clear cell renal cell carcinoma (ccRCC) is unclear. Thus, we aimed to establish a prognostic model according to VT to predict overall survival of ccRCC patients.
METHODS: We used patient data from TCGA database and built a prognostic model with 13 VT-related genes (VTRGs) by differential expression analysis, LASSO regression, and univariate/multivariate Cox analysis. The model was validated internally and externally, and survival analysis and ROC curves depicted excellent predictive ability. Furthermore, higher modeled riskscores corresponded to more advanced tumor progression. To further understand the potential reasons for different prognoses in patients, we did enrichment analysis on differentially expressed genes identified by the model in risk groups. The expression levels and roles of SAA1 and KIF18B in ccRCC were verified by qRT-PCR and cell function experiments.
RESULTS: Humoral immune response and cAMP signaling pathway may be the biological processes and pathways leading to poor prognosis. Further analysis of immune microenvironment presented that ccRCC patients with poor prognoses had highly immune-infiltrated characteristics. We compared the drug response data of samples from different prognostic patients in the GDSC database and identified drug sensitivity differences associated with prognosis. Finally, we demonstrated that SAA1 and KIF18B could increase the proliferation, migration, and invasion ability of ccRCC cells using cellular experiments.
CONCLUSIONS: In summary, we further revealed the importance of VTRGs in ccRCC prognosis.
METHODS: We used patient data from TCGA database and built a prognostic model with 13 VT-related genes (VTRGs) by differential expression analysis, LASSO regression, and univariate/multivariate Cox analysis. The model was validated internally and externally, and survival analysis and ROC curves depicted excellent predictive ability. Furthermore, higher modeled riskscores corresponded to more advanced tumor progression. To further understand the potential reasons for different prognoses in patients, we did enrichment analysis on differentially expressed genes identified by the model in risk groups. The expression levels and roles of SAA1 and KIF18B in ccRCC were verified by qRT-PCR and cell function experiments.
RESULTS: Humoral immune response and cAMP signaling pathway may be the biological processes and pathways leading to poor prognosis. Further analysis of immune microenvironment presented that ccRCC patients with poor prognoses had highly immune-infiltrated characteristics. We compared the drug response data of samples from different prognostic patients in the GDSC database and identified drug sensitivity differences associated with prognosis. Finally, we demonstrated that SAA1 and KIF18B could increase the proliferation, migration, and invasion ability of ccRCC cells using cellular experiments.
CONCLUSIONS: In summary, we further revealed the importance of VTRGs in ccRCC prognosis.
摘要：
背景：囊泡运输（VT）与肿瘤进展和免疫力有复杂的关系。但是室性心动过速在透明细胞肾细胞癌（ccRCC）中的预后意义尚不清楚。因此，我们旨在根据VT建立预后模型来预测ccRCC患者的总生存期。
方法：我们使用来自TCGA数据库的患者数据，并通过差异表达分析建立了具有13个VT相关基因（VTRGs）的预后模型，LASSO回归,和单变量/多变量Cox分析。该模型进行了内部和外部验证，生存分析和ROC曲线显示出优异的预测能力。此外，更高的模型风险评分对应于更晚期的肿瘤进展.为了进一步了解患者不同预后的潜在原因，我们对该模型在风险组中鉴定的差异表达基因进行了富集分析.通过qRT-PCR和细胞功能实验验证了SAA1和KIF18B在ccRCC中的表达水平和作用。
结果：体液免疫反应和cAMP信号通路可能是导致预后不良的生物学过程和通路。对免疫微环境的进一步分析表明，预后不良的ccRCC患者具有高度的免疫浸润特征。我们比较了GDSC数据库中来自不同预后患者的样品的药物反应数据，并确定了与预后相关的药物敏感性差异。最后,我们证明了SAA1和KIF18B可以增加增殖，迁移,细胞实验和ccRCC细胞的侵袭能力。
结论：总之，我们进一步揭示了VTRGs在ccRCC预后中的重要性。
方法：我们使用来自TCGA数据库的患者数据，并通过差异表达分析建立了具有13个VT相关基因（VTRGs）的预后模型，LASSO回归,和单变量/多变量Cox分析。该模型进行了内部和外部验证，生存分析和ROC曲线显示出优异的预测能力。此外，更高的模型风险评分对应于更晚期的肿瘤进展.为了进一步了解患者不同预后的潜在原因，我们对该模型在风险组中鉴定的差异表达基因进行了富集分析.通过qRT-PCR和细胞功能实验验证了SAA1和KIF18B在ccRCC中的表达水平和作用。
结果：体液免疫反应和cAMP信号通路可能是导致预后不良的生物学过程和通路。对免疫微环境的进一步分析表明，预后不良的ccRCC患者具有高度的免疫浸润特征。我们比较了GDSC数据库中来自不同预后患者的样品的药物反应数据，并确定了与预后相关的药物敏感性差异。最后,我们证明了SAA1和KIF18B可以增加增殖，迁移,细胞实验和ccRCC细胞的侵袭能力。
结论：总之，我们进一步揭示了VTRGs在ccRCC预后中的重要性。
