Department of Urology Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China.
Department of Emergency Surgery, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, 450000, China.
BMC Cancer. 2023 Jul 18;23(1):674. doi: 10.1186/s12885-023-11165-x.
Annexins are a family of proteins involved in a wide variety of cellular processes such as inflammation, proliferation, differentiation, apoptosis, migration and membrane repair. However, the role of most Annexins in renal cell carcinoma (RCC) remained unclear.
The differentially expressed Annexins in RCC compared with normal controls were screened applying the TCGA database. The correlation of differentially expressed Annexins with clinical stages, grades and overall survival was analyzed to explore the clinical significance of Annexins in RCC. Then ANXA8 was selected and further stained in the discover and validation RCC cohort. The correlation of ANXA8 expression with clinical parameter was verified at the protein level. To explore the potential function of ANXA8, ANXA8 was knockdown in the RCC cell line and further analyzed using transcriptome and bioinformatic analysis.
mRNA expression of ANXA1, ANXA2R, ANXA4, ANXA8, ANXA8L1 and ANXA13 were significantly upregulated in RCC compared with normal kidney tissues. In contrast, ANXA3 and ANXA9 mRNA expression was significantly downregulated. Higher expression of ANXA2R, ANXA8 and ANXA8L1 were correlated with worse overall survival, while lower expression of ANXA3, ANXA9 and ANXA13 were associated with worse clinical outcomes in RCC patients. We further demonstrated that ANXA8 expression was significantly increased in RCC compared with normal renal tissues at the protein level. And higher protein expression of ANXA8 was associated with higher clinical grades. Through the bioinformatics analysis and cell cycle analysis, we found knockdown of ANXA8 mainly influenced the cell cycle and DNA replication. The top ten hub genes consist of CDC6, CDK2, CHEK1, CCNB1, ORC1, CHEK2, MCM7, CDK1, PCNA and MCM3.
Multiple members of Annexins were abnormally expressed and associated with the prognosis of RCC. The expression of ANXA8 was significantly increased in RCC and associated with poor prognosis. ANXA8 might influence the cell cycle and could be a potential biomarker and therapeutic target for RCC.
膜联蛋白是一类参与多种细胞过程的蛋白质，如炎症、增殖、分化、凋亡、迁移和膜修复。然而，大多数膜联蛋白在肾细胞癌 (RCC) 中的作用仍不清楚。
应用 TCGA 数据库筛选出与正常对照相比在 RCC 中差异表达的膜联蛋白。分析差异表达的膜联蛋白与临床分期、分级和总生存期的相关性，以探讨膜联蛋白在 RCC 中的临床意义。然后选择 ANXA8 并在发现和验证 RCC 队列中进一步染色。在蛋白质水平上验证 ANXA8 表达与临床参数的相关性。为了探讨 ANXA8 的潜在功能，在 RCC 细胞系中敲低 ANXA8，并进一步通过转录组和生物信息学分析进行分析。
与正常肾组织相比，RCC 中 ANXA1、ANXA2R、ANXA4、ANXA8、ANXA8L1 和 ANXA13 的 mRNA 表达明显上调。相反，ANXA3 和 ANXA9 的 mRNA 表达明显下调。ANXA2R、ANXA8 和 ANXA8L1 的高表达与总体生存率较差相关，而 ANXA3、ANXA9 和 ANXA13 的低表达与 RCC 患者的临床结局较差相关。我们进一步证明，与正常肾组织相比，RCC 中 ANXA8 的蛋白表达明显增加。并且 ANXA8 蛋白表达较高与较高的临床分级相关。通过生物信息学分析和细胞周期分析，我们发现敲低 ANXA8 主要影响细胞周期和 DNA 复制。前 10 个枢纽基因包括 CDC6、CDK2、CHEK1、CCNB1、ORC1、CHEK2、MCM7、CDK1、PCNA 和 MCM3。
多种膜联蛋白异常表达，并与 RCC 的预后相关。ANXA8 在 RCC 中的表达明显增加，并与不良预后相关。ANXA8 可能影响细胞周期，可能成为 RCC 的潜在生物标志物和治疗靶点。
