人类白细胞抗原E表达与实体瘤预后之间的关联：一项系统评价和荟萃分析
Association between human leukocyte antigen E expression and outcomes in solid tumors: a systematic review and meta-analysis.
作者信息
Benitez Fuentes Javier David, Bartolome Arcilla Jorge, Lazaro Sanchez Antonio David, de Luna Aguilar Alicia, Mohamed Mohamed Kauzar, Guevara-Hoyer Kissy, Ballestin Martinez Pablo, Borregon Rivilla Miguel, Ferrandez Arias Asia, Sánchez-Ramon Silvia, Ocaña Alberto
机构信息
Department of Medical Oncology, Elche General University Hospital, Alicante, Spain.
Department of Medical Oncology, Hospital Clinico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), and CIBERONC, Madrid, Spain.
出版信息
Front Oncol. 2025 Feb 24;15:1525924. doi: 10.3389/fonc.2025.1525924. eCollection 2025.
BACKGROUND
Immunotherapy has gained momentum with the discovery of novel antibodies targeting immunosuppressive proteins. HLA-E, a non-classical major histocompatibility complex class I (MHC-I) protein, exhibits immunosuppressive properties, potentially influencing tumor immune evasion mechanisms. The association between Human Leukocyte Antigen E (HLA-E) expression and outcomes in solid tumors remains unclear.
METHODS
A systematic review of MEDLINE, Scopus, and the Cochrane Library up to March 15, 2024, was conducted following the PRISMA guidelines. Studies investigating HLA-E expression in solid tumors and its association with OS and DFS were included. Statistical analysis was performed using Comprehensive Meta-Analysis (version 3.0) with random-effects models.
RESULTS
After screening 657 articles, 11 studies were included, comprising a total of 1781 patients. The studies encompassed a variety of cancer types, follow-up periods, and staging details, with the majority focusing on non-metastatic cases. Notably, three studies evaluated colorectal cancer, while others focused on pancreatic, esophageal, brain, renal cell, gastric, endometrial, cervical, and hepatocellular carcinomas. The mean age of the patients was 59.81 ± 2.01 years, and the median follow-up period was 57.45 ± 8.91 months. HLA-E expression demonstrated no statistically significant association with OS (HR 0.913, 95% CI = 0.567-1.469; P=0.707), with significant heterogeneity observed (I2 = 84%). However, HLA-E non-expression was significantly associated with improved DFS (HR 1.406, 95% CI = 1.027-1.930; P=0.03), with moderate heterogeneity (I2 = 45%).
CONCLUSION
This systematic review highlights that HLA-E expression in solid tumors could be a biomarker of better prognosis, measured by DFS. These findings align with the clinical benefit observed for agents targeting this pathway. However, further studies should be performed to confirm these preliminary observations.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024527598, identifier CRD42024527598.
背景
随着针对免疫抑制蛋白的新型抗体的发现，免疫疗法得到了广泛应用。人类白细胞抗原E（HLA-E）是一种非经典的主要组织相容性复合体I类（MHC-I）蛋白，具有免疫抑制特性，可能影响肿瘤免疫逃逸机制。实体瘤中人类白细胞抗原E（HLA-E）表达与预后之间的关系仍不明确。
方法
按照PRISMA指南，对截至2024年3月15日的MEDLINE、Scopus和Cochrane图书馆进行了系统综述。纳入研究实体瘤中HLA-E表达及其与总生存期（OS）和无病生存期（DFS）关系的研究。使用综合Meta分析（版本3.0）和随机效应模型进行统计分析。
结果
在筛选了657篇文章后，纳入了11项研究，共1781例患者。这些研究涵盖了多种癌症类型、随访期和分期细节，大多数关注非转移性病例。值得注意的是，三项研究评估了结直肠癌，其他研究则关注胰腺癌、食管癌、脑癌、肾细胞癌、胃癌、子宫内膜癌、宫颈癌和肝细胞癌。患者的平均年龄为59.81±2.01岁，中位随访期为57.45±8.91个月。HLA-E表达与OS无统计学显著关联（风险比[HR]0.913，95%置信区间[CI]=0.567-1.469；P=0.707），观察到显著异质性（I2=84%）。然而，HLA-E不表达与DFS改善显著相关（HR 1.406，95%CI=1.027-1.930；P=0.03），异质性中等（I2=45%）。
结论
本系统综述强调，实体瘤中HLA-E表达可能是通过DFS衡量的更好预后的生物标志物。这些发现与针对该途径的药物所观察到的临床益处一致。然而，应进行进一步研究以证实这些初步观察结果。
系统综述注册
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024527598，标识符CRD42024527598。
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