Zhu Zhenpeng, Ji Xing, Zhu Weijie, Cai Tianyu, Xu Chunru, Huang Cong, He Shiming, Gong Yanqing, Li Xuesong, Lin Jian, Zhou Liqun
Department of Urology, Peking University First Hospital, Beijing 100034, China.
Institution of Urology, Peking University, Beijing 100034, China.
J Cancer. 2021 Oct 17;12(23):7101-7110. doi: 10.7150/jca.61972. eCollection 2021.
At present, how early screening for ccRCC is still a thorny issue for urologists. Probing the mechanisms underlying the development of ccRCC and finding relevant prognostic biomarkers remains crucial. Therefore, we systematically analyzed the APOBEC family in this study and identified APOBEC3D as a prognostic biomarker. In this study, based on the TCGA database, we systematically assessed the expression and prognosis of the APOBEC family and analyzed potential bioinformatic pathways. We then constructed nomograms to predict the prognosis of ccRCC patients better. Afterward, we further focused on APOBEC3D in our data on ccRCC specimens. The APOBEC3D should be extensively studied in ccRCC in the future. The results showed that the APOBEC family showed the most significant changes in expression in ccRCC. The pathway enrichment analysis showed that APOBEC3 family members mainly regulated cytidine and cytosine-related processes. Subsequently, the Cox regression was used to construct prognostic signature, and validated in ICGC and GEO databases. Next, a nomogram was created integrating clinical parameters showing good predictive performance. Finally, we screened for APOBEC3D and found in our clinical sample that patients with high expression of APOBEC3D had a worse prognosis. Based on these results, APOBEC family members play important roles in the development of ccRCC, and APOBEC3D could serve as the biomarker for predicting patient prognosis.
目前，如何早期筛查肾透明细胞癌（ccRCC）对泌尿外科医生来说仍是一个棘手的问题。探究ccRCC发生发展的机制并寻找相关的预后生物标志物仍然至关重要。因此，我们在本研究中对载脂蛋白B mRNA编辑酶催化多肽样家族（APOBEC家族）进行了系统分析，并将载脂蛋白B mRNA编辑酶催化多肽样3D（APOBEC3D）鉴定为一种预后生物标志物。在本研究中，基于癌症基因组图谱（TCGA）数据库，我们系统评估了APOBEC家族的表达和预后，并分析了潜在的生物信息学通路。然后我们构建了列线图以更好地预测ccRCC患者的预后。之后，我们在ccRCC标本数据中进一步聚焦于APOBEC3D。未来应在ccRCC中对APOBEC3D进行广泛研究。结果显示，APOBEC家族在ccRCC中的表达变化最为显著。通路富集分析表明，APOBEC3家族成员主要调控胞苷和胞嘧啶相关过程。随后，使用Cox回归构建预后特征，并在国际癌症基因组联盟（ICGC）和基因表达综合数据库（GEO）中进行验证。接下来，创建了一个整合临床参数的列线图，显示出良好的预测性能。最后，我们筛选了APOBEC3D，发现在我们的临床样本中，APOBEC3D高表达的患者预后较差。基于这些结果，APOBEC家族成员在ccRCC的发生发展中起重要作用，且APOBEC3D可作为预测患者预后的生物标志物。
