Table_1_Pan-Cancer analysis and experimental validation identify the oncogenic nature of ESPL1: Potential therapeutic target in colorectal cancer.docx

IntroductionExtra 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.
MethodsHerein, 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.
ResultsThe 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.
DiscussionTaken 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.

引言：类纺锤体极体样蛋白1（Extra spindle pole bodies like 1，ESPL1）是细胞周期持续运转所必需的，其核心功能是启动姐妹染色单体的最终分离。尽管既往研究已揭示ESPL1与癌症发生发展存在关联，但目前尚未有针对该基因的系统性泛癌分析（pan-cancer analysis）。本研究结合多组学数据（multi-omics data）与生物信息学方法，全面解析了ESPL1在癌症中的功能；此外，我们还检测了ESPL1对多种癌细胞系增殖的影响，并通过结直肠癌患者来源的类器官（organoids）验证了ESPL1与药物敏感性的关联。以上研究结果均证实了ESPL1的癌基因特性。
方法：本研究从多个公开数据库下载原始数据，借助R软件与在线工具，探究ESPL1的表达水平与患者预后、生存情况、肿瘤微环境（tumor microenvironment）、肿瘤异质性（tumor heterogeneity）及突变谱（mutational profiles）之间的关联。为验证ESPL1的癌基因特性，我们在多种癌细胞系中对该靶基因进行敲低（knockdown）实验，以验证其对细胞增殖与迁移的影响；此外，还采用患者来源类器官验证药物敏感性。
结果：本研究发现，与正常组织相比，ESPL1在肿瘤组织中显著高表达；且ESPL1高表达与多种癌症的不良预后显著相关。进一步分析显示，基于多项肿瘤异质性指标，ESPL1高表达的肿瘤往往具有更高的异质性。富集分析表明，ESPL1参与调控多条癌症相关通路。值得注意的是，本研究发现干扰ESPL1的表达可显著抑制肿瘤细胞的增殖。此外，类器官中ESPL1的表达水平越高，其对PHA-793887、PAC-1及AZD7762的敏感性越强。
讨论：综上，本研究证实ESPL1可能参与多种癌症的发生与疾病进展，提示其有望作为预后标志物（prognostic indicator）与治疗靶点（therapeutic target）。