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CD44过表达作为口腔癌耐药的介导因素:一项揭示分子基础和治疗意义的荟萃分析

CD44 overexpression as a mediator of drug resistance in oral cancer: a meta-analysis unveiling molecular underpinnings and therapeutic implications.

作者信息

Miao Shushu, Wang Caiqiong, Zheng Anqi

机构信息

Department of Stomatology, Wenzhou People's Hospital, Wenzhou, Zhejiang Province, 325000, China.

Pediatric Dentistry, School & Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, China.

出版信息

Discov Oncol. 2025 Aug 29;16(1):1650. doi: 10.1007/s12672-025-03436-9.

DOI:10.1007/s12672-025-03436-9
PMID:40879964
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12397467/
Abstract

BACKGROUND

Therapeutic resistance in oral cancer, with cancer stem cells (CSCs) playing a pivotal role, remains a major clinical challenge. CD44, a key CSC marker, has been implicated in multidrug resistance mechanisms through drug efflux, DNA repair, and anti-apoptotic pathways. This meta-analysis aims to systematically evaluate the association between CD44 expression and clinicopathological characteristics in oral cancer patients through analysis of controlled clinical studies.

METHODS

We systematically searched PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, VIP, WanFang, and China Biomedical Literature Database from inception to September 2022. Controlled clinical studies examining CD44 overexpression in relation to clinicopathological characteristics and survival outcomes in oral cancer patients were included. Quality assessment was performed using the Newcastle-Ottawa Scale. Data were analyzed using RevMan 5.3 software.

RESULTS

Ten high-quality studies comprising 846 oral cancer patients were included. CD44 overexpression was significantly associated with advanced local tumor invasion (T category: OR: 1.38; 95% CI 1.14-1.66; P < 0.001; I²=25%). No significant associations were found with N category, histological grade, or vascular invasion. Pooled survival analysis was limited by heterogeneous reporting methods across studies.

CONCLUSION

CD44 overexpression serves as a molecular marker of therapeutic resistance in oral cancer, particularly associated with local tumor progression. These findings highlight CD44-targeted therapies as promising strategies to overcome treatment resistance. Future large-scale, multicenter trials are needed to validate CD44 isoforms as prognostic biomarkers and therapeutic targets.

摘要

背景

口腔癌中的治疗耐药性仍然是一个重大的临床挑战,癌症干细胞(CSCs)在其中起关键作用。CD44作为一种关键的癌症干细胞标志物,已通过药物外排、DNA修复和抗凋亡途径参与多药耐药机制。本荟萃分析旨在通过对对照临床研究的分析,系统评估CD44表达与口腔癌患者临床病理特征之间的关联。

方法

我们系统检索了从数据库建立至2022年9月的PubMed、EMBASE、Cochrane图书馆、Web of Science、中国知网、维普、万方和中国生物医学文献数据库。纳入了研究CD44过表达与口腔癌患者临床病理特征及生存结果关系的对照临床研究。使用纽卡斯尔-渥太华量表进行质量评估。采用RevMan 5.3软件进行数据分析。

结果

纳入了10项高质量研究,共846例口腔癌患者。CD44过表达与局部肿瘤晚期侵袭显著相关(T分期:OR:1.38;95%CI 1.14-1.66;P<0.001;I²=25%)。在N分期、组织学分级或血管侵犯方面未发现显著关联。由于各研究报告方法的异质性限制了汇总生存分析。

结论

CD44过表达是口腔癌治疗耐药的分子标志物,尤其与局部肿瘤进展相关。这些发现突出了以CD44为靶点的治疗作为克服治疗耐药性的有前景策略。未来需要大规模、多中心试验来验证CD44异构体作为预后生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27da/12397467/6e25497a441d/12672_2025_3436_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27da/12397467/f03dca8ebdf2/12672_2025_3436_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27da/12397467/80f2a1f6767e/12672_2025_3436_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27da/12397467/c1966c59519b/12672_2025_3436_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27da/12397467/b2b1350faa7f/12672_2025_3436_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27da/12397467/6e25497a441d/12672_2025_3436_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27da/12397467/f03dca8ebdf2/12672_2025_3436_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27da/12397467/80f2a1f6767e/12672_2025_3436_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27da/12397467/c1966c59519b/12672_2025_3436_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27da/12397467/b2b1350faa7f/12672_2025_3436_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27da/12397467/6e25497a441d/12672_2025_3436_Fig9_HTML.jpg

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本文引用的文献

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High CD44 Immunoexpression Correlates with Poor Overall Survival: Assessing the Role of Cancer Stem Cell Markers in Oral Squamous Cell Carcinoma Patients from the High-Risk Population of Pakistan.高 CD44 免疫表达与总生存不良相关:评估巴基斯坦高危人群口腔鳞状细胞癌患者中癌症干细胞标志物的作用。
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CD44 and ALDH1 immunoexpression as prognostic indicators of invasion and metastasis in oral squamous cell carcinoma.CD44 和 ALDH1 的免疫表达可作为口腔鳞状细胞癌侵袭和转移的预后指标。
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