Clinical relevance of ORCs in predicting prognosis and immunotherapy outcomes: A pan-cancer analysis

IF 2.5 4区医学 Q3 IMMUNOLOGY Immunobiology Pub Date : 2024-01-10 DOI:10.1016/j.imbio.2024.152783

Yajun Zhao , Jiangtao Wang , Xiaodong Liang , Chen Wang

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Abstract

Background

The origin recognition complex (ORC) consists of six subunits and mediates DNA replication by binding to its origin. Recent studies show that ORCs are closely related to various biological processes in tumors. However, a comprehensive study of ORCs in pan-cancer has not been conducted.

Results

A systematic evaluation of the expression, mutation, and prognostic significance of ORCs was conducted across cancer types using data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. The single-sample Gene Set Enrichment Analysis (ssGSEA) was performed using R package “Gene Set Variation Analysis (GSVA)” to evaluate ORC score. ORC score was significantly elevated in most cancers and linked with an inferior prognosis. It was positively related to the G2/M checkpoint and DNA repair pathways. An elevated ORC score also correlated with tumor mutation burden (TMB)/ microsatellite instability (MSI). A prognosis analysis suggested that high ORC scores were associated with heightened immunotherapeutic sensitivity.

Conclusions

Our research elucidates the genomic changes associated with and clinical relevance of ORCs in cancer and provides unique insights for future investigation of ORCs in immunotherapy.

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ORC 在预测预后和免疫疗法结果方面的临床意义：泛癌症分析

背景起源识别复合体（ORC）由六个亚基组成，通过与起源结合来介导 DNA 复制。最近的研究表明，ORC与肿瘤的各种生物学过程密切相关。结果利用癌症基因组图谱（TCGA）和基因型-组织表达（GTEx）数据库的数据，对不同癌症类型中 ORCs 的表达、突变和预后意义进行了系统评估。利用R软件包 "基因组变异分析（GSVA）"进行了单样本基因组富集分析（ssGSEA），以评估ORC得分。大多数癌症的 ORC 评分都明显升高，并与预后不良有关。它与 G2/M 检查点和 DNA 修复途径呈正相关。ORC 评分的升高还与肿瘤突变负荷（TMB）/微卫星不稳定性（MSI）相关。结论：我们的研究阐明了与癌症中 ORCs 相关的基因组变化及其临床意义，并为未来研究 ORCs 在免疫疗法中的应用提供了独特的见解。

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来源期刊

Immunobiology 医学-免疫学

CiteScore

5.00

自引率

3.60%

发文量

108

审稿时长

55 days

期刊介绍： Immunobiology is a peer-reviewed journal that publishes highly innovative research approaches for a wide range of immunological subjects, including • Innate Immunity, • Adaptive Immunity, • Complement Biology, • Macrophage and Dendritic Cell Biology, • Parasite Immunology, • Tumour Immunology, • Clinical Immunology, • Immunogenetics, • Immunotherapy and • Immunopathology of infectious, allergic and autoimmune disease.