The Potential of ESCO2 as a Prognostic and Immunotherapeutic Marker of Pan-Cancer and Its Role in Anti-PD-1 Treatment of Bladder Cancer.

IF 2.5 3区医学 Q3 ONCOLOGY

Oncology Pub Date : 2024-11-11 DOI:10.1159/000542188

Wei Guo, Shuo Zhao, Keqiang Yan, Yidong Fan, Jikai Liu

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引用次数: 0

Abstract

Introduction: Establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2), a member of the EFO2 family, is implicated in the pathogenesis and progression of various cancers. However, there has been limited comprehensive pan-cancer analysis conducted on ESCO2 thus far.

Methods: Publicly available databases, such as the UCSC Xena database, were utilized to examine differential expression patterns across various cancer types. In addition, variations in expression levels were investigated across distinct clinical stages. Univariate Cox regression and Kaplan-Meier survival analyses were conducted to evaluate the impact on overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI) at the pan-cancer level. The correlation between ESCO2 expression and immune cell infiltration was examined to gain insight into the tumor microenvironment (TME) in different cancers. The results of the bioinformatic analysis were validated using immunotherapy clinical trials and pathological specimens. CCK-8 and Transwell assay experiments were performed to investigate the biological function of ESCO2.

Results: ESCO2 expression was found to be upregulated in most cancers, with a correlation to TNM stages. Prognostic analysis indicated that overexpression of ESCO2 was associated with poor prognosis in various cancers. Furthermore, the correlation between ESCO2 expression and immune cell infiltration suggested its potential as a predictor for immunotherapy efficacy. Notably, ESCO2 expression showed positive associations with immunoinhibitor, immunostimulator, major histocompatibility complex (MHC) molecule, chemokine receptor, tumor mutation burden (TMB), and microsatellite instability (MSI) levels in bladder cancer (BLCA). The validation cohort for immunotherapy corroborated these findings and substantiated that ESCO2 could function as an autonomous prognostic biomarker and a promising target for cancer treatment via immunotherapy. In addition, in vitro experiments confirmed the role of ESCO2 in influencing the proliferation, invasion, and migration of BLCA cells.

Conclusion: ESCO2 participates in regulating the immune infiltration and affecting the prognosis of patients in many cancers, especially in BLCA. ESCO2 may serve as a prognostic and immunotherapy biomarker in future treatment of human cancer.

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ESCO2 作为泛癌症预后和免疫治疗标志物的潜力及其在膀胱癌抗 PD1 治疗中的作用。

背景姐妹染色单体内聚N-乙酰转移酶2（ESCO2）是EFO2家族的成员之一，它与多种癌症的发病和进展有关。然而，迄今为止对 ESCO2 进行的全面泛癌症分析还很有限。方法利用可公开获得的数据库（如 UCSC Xena 数据库）来研究各种癌症类型的差异表达模式。此外，还研究了不同临床分期的表达水平变化。进行了单变量 Cox 回归和 Kaplan-Meier 生存分析，以评估在泛癌症水平上对总生存期（OS）、疾病特异性生存期（DSS）、无病间隔期（DFI）和无进展间隔期（PFI）的影响。研究还考察了 ESCO2 表达与免疫细胞浸润之间的相关性，以深入了解不同癌症的肿瘤微环境。生物信息学分析的结果通过免疫疗法临床试验和病理标本进行了验证。为研究 ESCO2 的生物功能，还进行了 CCK-8 和跨孔板实验。结果发现 ESCO2 在大多数癌症中表达上调，并与 TNM 分期相关。预后分析表明，ESCO2的过表达与各种癌症的不良预后有关。此外，ESCO2 的表达与免疫细胞浸润之间的相关性表明，ESCO2 有可能成为免疫疗法疗效的预测因子。值得注意的是，ESCO2的表达与膀胱癌（BLCA）中的免疫抑制剂、免疫刺激剂、MHC分子、趋化因子受体、肿瘤突变负荷（TMB）和微卫星不稳定性（MSI）水平呈正相关。用于免疫疗法的验证队列证实了这些发现，并证实 ESCO2 可作为一种自主预后生物标志物和一种有希望通过免疫疗法治疗癌症的靶点。此外，体外实验证实了 ESCO2 在促进 BLCA 细胞增殖、侵袭和迁移方面的作用。结论 ESCO2 参与调节免疫浸润并影响多种癌症患者的预后，尤其是 BLCA。ESCO2 可作为预后和免疫治疗的生物标志物，用于未来人类癌症的治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Oncology 医学-肿瘤学

CiteScore

6.00

自引率

2.90%

发文量

审稿时长

6-12 weeks

期刊介绍： Although laboratory and clinical cancer research need to be closely linked, observations at the basic level often remain removed from medical applications. This journal works to accelerate the translation of experimental results into the clinic, and back again into the laboratory for further investigation. The fundamental purpose of this effort is to advance clinically-relevant knowledge of cancer, and improve the outcome of prevention, diagnosis and treatment of malignant disease. The journal publishes significant clinical studies from cancer programs around the world, along with important translational laboratory findings, mini-reviews (invited and submitted) and in-depth discussions of evolving and controversial topics in the oncology arena. A unique feature of the journal is a new section which focuses on rapid peer-review and subsequent publication of short reports of phase 1 and phase 2 clinical cancer trials, with a goal of insuring that high-quality clinical cancer research quickly enters the public domain, regardless of the trial’s ultimate conclusions regarding efficacy or toxicity.