Prognostic significance of biomarker expression on immunohistochemistry for overall survival in osteosarcoma: An overview of systematic reviews

Q2 Medicine

Journal of Clinical Orthopaedics and Trauma Pub Date : 2026-01-01 Epub Date: 2025-11-12 DOI:10.1016/j.jcot.2025.103264

Duddukunta Vishal Reddy, Aritra Chattopadhyay, Madhubari Vathulya, Mohit Dhingra

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Abstract

Background

To summarize evidence from systematic reviews on the prognostic value of tissue immunohistochemistry biomarkers in predicting overall survival in patients with osteosarcoma.

Methodology

The Overview was prospectively registered on PROSPERO (ID Number: CRD42024615273), and a comprehensive search of Cochrane Database, PubMed, EMBASE, and Web of Science was conducted for all systematic reviews (SRs) published in English using the term ‘osteosarcoma’. Eligible SRs reported survival prognostication of IHC-detected tumor biomarkers using hazard ratios (HR) as the effect measure. These SRs contained primary studies exclusively involving participants with bone and soft tissue sarcomas. The AMSTAR-2 tool was used to assess the risk of bias, and the GRADE framework was applied to evaluate the certainty of synthesized evidence.

Results

The search yielded 1467 systematic reviews, of which 10 SRs comprising 5288 participants met the inclusion criteria. Overexpression of Ezrin (HR: 3.15 [2.39–4.14], p < 0.001), HIF-1α (HR: 2.6 [2.09–3.24], p < 0.001), p53 (HR: 2.49 [1.50–4.12], p < 0.001), VEGF (HR: 2.42 [1.87–3.11], p < 0.001), IGF-1R (HR: 2.2 [1.36–3.03], p < 0.001), CXCR4 (HR: 2.13 [1.78–2.55], p < 0.001), HER2 (HR: 2.03 [1.36–3.03], p < 0.001), PD-L1 (HR: 1.72 [1.30–2.28], p < 0.001), and CD44V6 (HR: 1.53 [1.25–1.88], p < 0.001) was significantly associated with poorer survival outcomes. Conversely, p16 expression (HR: 0.33 [0.02–5.74], p = 0.448) suggested a protective effect, though not statistically significant. The certainty of evidence varied from very low to high, while AMSTAR-2 ratings for the included SRs ranged from critically low to low.

Conclusions

Overexpression of VEGF, HIF-1α, Ezrin, and p53 was strongly associated with increased mortality risk in osteosarcoma. These findings may guide patient counselling, biomarker panel optimization, and the development of targeted therapies.

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免疫组化生物标志物表达对骨肉瘤总生存期的预后意义：系统综述

背景：总结来自系统综述的关于组织免疫组化生物标志物在预测骨肉瘤患者总生存期方面的预后价值的证据。本综述前瞻性地在PROSPERO上注册（ID号：CRD42024615273），并对Cochrane数据库、PubMed、EMBASE和Web of Science进行全面检索，检索所有使用“骨肉瘤”一词发表的英文系统综述（SRs）。符合条件的SRs报告了ihc检测的肿瘤生物标志物的生存预后，使用风险比（HR）作为效果衡量标准。这些SRs包含了专门涉及骨和软组织肉瘤患者的初步研究。AMSTAR-2工具用于评估偏倚风险，GRADE框架用于评估综合证据的确定性。结果共检索到1467篇系统评价，其中10篇系统评价（5288名受试者）符合纳入标准。超表达Ezrin(人力资源:3.15 (2.39 - -4.14),p & lt; 0.001), HIF-1α(人力资源:2.6 (2.09 - -3.24),p & lt; 0.001), p53(人力资源:2.49 (1.50 - -4.12),p & lt; 0.001), VEGF(人力资源:2.42 (1.87 - -3.11),p & lt; 0.001), IGF-1R(人力资源:2.2 (1.36 - -3.03),p & lt; 0.001),趋化因子受体CXCR4(人力资源:2.13 (1.78 - -2.55),p & lt; 0.001), HER2(人力资源:2.03 (1.36 - -3.03),p & lt; 0.001), PD-L1(人力资源:1.72 (1.30 - -2.28),p & lt; 0.001),和CD44V6(人力资源:1.53 (1.25 - -1.88),p & lt; 0.001)与贫穷的生存结果显著相关。相反，p16表达（HR: 0.33 [0.02-5.74], p = 0.448）提示有保护作用，但无统计学意义。证据的确定性从非常低到高不等，而纳入的SRs的AMSTAR-2评级从极低到低不等。结论VEGF、HIF-1α、Ezrin和p53的过表达与骨肉瘤死亡风险增高密切相关。这些发现可以指导患者咨询，生物标志物面板优化和靶向治疗的发展。

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

Journal of Clinical Orthopaedics and Trauma Medicine-Orthopedics and Sports Medicine

CiteScore

4.30

自引率

0.00%

发文量

181

审稿时长

92 days

期刊介绍： Journal of Clinical Orthopaedics and Trauma (JCOT) aims to provide its readers with the latest clinical and basic research, and informed opinions that shape today''s orthopedic practice, thereby providing an opportunity to practice evidence-based medicine. With contributions from leading clinicians and researchers around the world, we aim to be the premier journal providing an international perspective advancing knowledge of the musculoskeletal system. JCOT publishes content of value to both general orthopedic practitioners and specialists on all aspects of musculoskeletal research, diagnoses, and treatment. We accept following types of articles: • Original articles focusing on current clinical issues. • Review articles with learning value for professionals as well as students. • Research articles providing the latest in basic biological or engineering research on musculoskeletal diseases. • Regular columns by experts discussing issues affecting the field of orthopedics. • "Symposia" devoted to a single topic offering the general reader an overview of a field, but providing the specialist current in-depth information. • Video of any orthopedic surgery which is innovative and adds to present concepts. • Articles emphasizing or demonstrating a new clinical sign in the art of patient examination is also considered for publication. Contributions from anywhere in the world are welcome and considered on their merits.