Department of Radiation Oncology, Division of Thoracic Oncology, Sichuan University West China Hospital, Chengdu, Sichuan, China.
College of Management, Sichuan Agricultural University, Yaan, Sichuan, China.
BMJ Open. 2024 Jan 31;14(1):e073887. doi: 10.1136/bmjopen-2023-073887.
This study aimed to systematically elucidate the prognostic significance of cyclin-dependent kinase subunit 2 (CKS2) expression in various cancers and its correlation with their clinicopathological characteristics.
In this meta-analysis and bioinformatic analysis, articles were identified through searches of multiple databases and meta-analysed according to the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols. Data from The Cancer Genome Atlas were examined using UCSC Xena tools to further confirm the prognostic effect of CKS2.
The PubMed, Embase, Web of Science and Cochrane Library databases were searched for articles published from their inception to 1 January 2023, using a combination of subject terms and free words, including 'CKS2', 'cancer', 'tumor', 'neoplasm', 'carcinoma', 'malignancy' and 'prognosis'.
The analysis included cohort or case-control studies, reported in English, with malignancy diagnoses confirmed by pathological methods, available HRs and 95% CIs for overall survival (OS) or extractable Kaplan-Meier curves, and a sample size of ≥20 patients. Reviews, commentaries, letters, conference reports, case reports, in vitro and animal studies, studies of gene variants, studies with sample cases from public databases and studies with unavailable survival or duplicated data were excluded.
Two researchers independently screened the articles, extracted the data and evaluated the quality of included studies using the Newcastle-Ottawa Scale. Meta-analysis and bioinformatic analyses were performed using the STATA and R software, respectively.
The analysis included 13 retrospective studies encompassing 1348 cases across 10 cancer types. Nine studies involving 1124 patients examined the correlation between CKS2 expression levels and OS. A fixed-effects model analysis revealed a significant association between high CKS2 expression and reduced OS (HR=2.27, 95% CI=1.87 to 2.77, p<0.001). Furthermore, high CKS2 expression was significantly associated with advanced tumour stage (relative risk (RR) = 1.82, 95% CI=1.57 to 2.11, p<0.001), lymph node metastasis (RR=1.68, 95% CI=1.38 to 2.04, p<0.001), larger tumour size (RR=1.60, 95% CI=1.27 to 2.03, p<0.001) and lower differentiation grade (RR=1.57, 95% CI=1.29 to 1.90, p<0.001). CKS2 expression levels were not significantly correlated with patients' age (RR=1.11, 95% CI=0.99 to 1.26, p=0.071) or sex (RR=0.98, 95% CI=0.90 to 1.07, p=0.653). An assessment of the articles showed no significant publication bias, confirming the robustness of these findings. The bioinformatic analysis further confirmed CKS2 upregulation in the examined cancer types and its association with poor OS in glioma (HR=1.97, 95% CI=1.78 to 2.18, p=3.70×10), liver hepatocellular carcinoma (HR=1.56, 95% CI=1.31 to 1.86, p=3.50×10) and lung adenocarcinoma (HR=1.27, 95% CI=1.10 to 1.48, p=1.70×10).
Elevated CKS2 expression is associated with poor prognosis in a subset of malignant tumours, highlighting its potential as a prognostic marker.
CRD42023394038.
本研究旨在系统阐明细胞周期蛋白依赖性激酶亚单位 2（CKS2）在各种癌症中的表达的预后意义及其与临床病理特征的相关性。
在这项荟萃分析和生物信息学分析中，通过多个数据库检索文章，并根据系统评价和荟萃分析报告的首选报告项目协议进行荟萃分析。使用 UCSC Xena 工具检查癌症基因组图谱的数据，以进一步确认 CKS2 的预后作用。
从其成立到 2023 年 1 月 1 日，使用主题术语和自由词组合，在 PubMed、Embase、Web of Science 和 Cochrane Library 数据库中搜索文章，包括'CKS2'、'癌症'、'肿瘤'、'肿瘤'、'癌'、'恶性肿瘤'和'预后'。
分析包括队列或病例对照研究，以英文发表，通过病理方法确诊为恶性肿瘤，有可提取的 HR 和 95%CI 用于总生存期（OS）或可提取的 Kaplan-Meier 曲线，且样本量≥20 例。排除综述、评论、信件、会议报告、病例报告、体外和动物研究、基因变异研究、从公共数据库中获取病例的研究以及无法获得生存数据或重复数据的研究。
两名研究人员独立筛选文章，使用纽卡斯尔-渥太华量表评估纳入研究的质量，并提取数据。使用 STATA 和 R 软件分别进行荟萃分析和生物信息学分析。
分析包括 13 项回顾性研究，涵盖 10 种癌症类型的 1348 例病例。9 项涉及 1124 名患者的研究检查了 CKS2 表达水平与 OS 的相关性。固定效应模型分析显示，高 CKS2 表达与降低 OS 显著相关（HR=2.27，95%CI=1.87-2.77，p<0.001）。此外，高 CKS2 表达与肿瘤分期较晚（相对风险（RR）=1.82，95%CI=1.57-2.11，p<0.001）、淋巴结转移（RR=1.68，95%CI=1.38-2.04，p<0.001）、肿瘤较大（RR=1.60，95%CI=1.27-2.03，p<0.001）和分化程度较低（RR=1.57，95%CI=1.29-1.90，p<0.001）显著相关。CKS2 表达水平与患者年龄（RR=1.11，95%CI=0.99-1.26，p=0.071）或性别（RR=0.98，95%CI=0.90-1.07，p=0.653）无显著相关性。对文章的评估表明，没有显著的发表偏倚，证实了这些发现的稳健性。生物信息学分析进一步证实了 CKS2 在检查的癌症类型中的上调及其与脑胶质瘤（HR=1.97，95%CI=1.78-2.18，p=3.70×10）、肝癌（HR=1.56，95%CI=1.31-1.86，p=3.50×10）和肺腺癌（HR=1.27，95%CI=1.10-1.48，p=1.70×10）中不良 OS 的相关性。
在一组恶性肿瘤中，CKS2 表达升高与预后不良相关，提示其可能作为一种预后标志物。
CRD42023394038。
