Cancer Center/Department of Colorectal Cancer Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Department of Colorectal Cancer Surgery, The Cancer Hospital of University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Science, Hangzhou, Zhejiang, China.
Front Immunol. 2023 Mar 16;14:1138077. doi: 10.3389/fimmu.2023.1138077. eCollection 2023.
Extra spindle pole bodies like 1 (ESPL1) are required to continue the cell cycle, and its primary role is to initiate the final segregation of sister chromatids. Although prior research has revealed a link between ESPL1 and the development of cancer, no systematic pan-cancer analysis has been conducted. Combining multi-omics data with bioinformatics, we have thoroughly described the function of ESPL1 in cancer. In addition, we examined the impact of ESPL1 on the proliferation of numerous cancer cell lines. In addition, the connection between ESPL1 and medication sensitivity was verified using organoids obtained from colorectal cancer patients. All these results confirm the oncogene nature of ESPL1.
Herein, we downloaded raw data from numerous publicly available databases and then applied R software and online tools to explore the association of ESPL1 expression with prognosis, survival, tumor microenvironment, tumor heterogeneity, and mutational profiles. To validate the oncogene nature of ESPL1, we have performed a knockdown of the target gene in various cancer cell lines to verify the effect of ESPL1 on proliferation and migration. In addition, patients' derived organoids were used to verify drug sensitivity.
The study found that ESPL1 expression was markedly upregulated in tumorous tissues compared to normal tissues, and high expression of ESPL1 was significantly associated with poor prognosis in a range of cancers. Furthermore, the study revealed that tumors with high ESPL1 expression tended to be more heterogeneous based on various tumor heterogeneity indicators. Enrichment analysis showed that ESPL1 is involved in mediating multiple cancer-related pathways. Notably, the study found that interference with ESPL1 expression significantly inhibited the proliferation of tumor cells. Additionally, the higher the expression of ESPL1 in organoids, the greater the sensitivity to PHA-793887, PAC-1, and AZD7762.
Taken together, our study provides evidence that ESPL1 may implicate tumorigenesis and disease progression across multiple cancer types, highlighting its potential utility as both a prognostic indicator and therapeutic target.
额外纺锤极体 1（ESPL1）等物质是继续细胞周期所必需的，其主要作用是启动姐妹染色单体的最终分离。尽管先前的研究表明 ESPL1 与癌症的发展有关，但尚未进行系统的泛癌症分析。本研究结合多组学数据和生物信息学，全面描述了 ESPL1 在癌症中的作用。此外，我们还研究了 ESPL1 对多种癌细胞系增殖的影响。此外，还使用从结直肠癌患者获得的类器官验证了 ESPL1 与药物敏感性之间的联系。所有这些结果都证实了 ESPL1 的癌基因性质。
在这里，我们从多个公开可用的数据库下载原始数据，然后应用 R 软件和在线工具来探索 ESPL1 表达与预后、生存、肿瘤微环境、肿瘤异质性和突变特征的关联。为了验证 ESPL1 的癌基因性质，我们在各种癌细胞系中敲低了靶基因，以验证 ESPL1 对增殖和迁移的影响。此外，还使用患者来源的类器官验证了药物敏感性。
研究发现，与正常组织相比，肿瘤组织中 ESPL1 的表达明显上调，并且在多种癌症中，ESPL1 高表达与预后不良显著相关。此外，研究还揭示了基于各种肿瘤异质性指标，高表达 ESPL1 的肿瘤往往更具异质性。富集分析表明，ESPL1 参与调节多种癌症相关途径。值得注意的是，研究发现干扰 ESPL1 表达可显著抑制肿瘤细胞的增殖。此外，类器官中 ESPL1 的表达越高，对 PHA-793887、PAC-1 和 AZD7762 的敏感性越高。
综上所述，本研究提供的证据表明，ESPL1 可能涉及多种癌症类型的肿瘤发生和疾病进展，突出了其作为预后指标和治疗靶点的潜在应用价值。
