Human leukocyte antigen-G isoform HLA-G2/6, but not HLA-G1/4/5, is an independent indicator of poor survival in patients with colorectal cancer

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Publicado en:Frontiers in Immunology vol. 16 (Oct 2025), p. 1672144-1672158
Autor principal: Zhang, Xia
Otros Autores: Qiu-Yue, Han, Zhang, Jian-Gang, Jiao, Lin, Wei-Hua, Yan, Lin, Aifen
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Frontiers Media SA
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022 |a 1664-3224 
024 7 |a 10.3389/fimmu.2025.1672144  |2 doi 
035 |a 3278326296 
045 2 |b d20251001  |b d20251031 
100 1 |a Zhang, Xia  |u Biological Resource Center, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang, China, Key Laboratory of Human Leukocyte antigen - G (HLA-G) Research & Development of Taizhou, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang, China 
245 1 |a Human leukocyte antigen-G isoform HLA-G2/6, but not HLA-G1/4/5, is an independent indicator of poor survival in patients with colorectal cancer 
260 |b Frontiers Media SA  |c Oct 2025 
513 |a Journal Article 
520 3 |a BackgroundHuman leukocyte antigen (HLA)-G has multiple isoforms with unique molecular structures and receptor-binding specificities. Different HLA-G isoform(s) may have distinct clinical relevance. Because of the lack of isoform-specific monoclonal antibodies (mAbs), the clinical significance of HLA-G isoforms (HLA-G1 to HLA-G7), except HLA-G1 and HLA-G5, remains largely unknown.MethodsIn this study, mAbs against HLA-G2/6 and HLA-G1/4/5 isoforms were generated and characterized. Expression of HLA-G2/6 and HLA-G1/4/5 isoforms was analyzed by immunohistochemistry, and clinical significance was evaluated retrospectively in 345 patients with colorectal cancer (CRC).ResultsThe expression rate of HLA-G2/6 (90/345, 26.1%) was significantly lower than that of HLA-G1/4/5 (275/345, 79.7%; p < 0.001). Patients with HLA-G2/6 expression had significantly poorer overall survival (OS) (median OS: 6.3 years [95% CI: 4.1–8.5] vs . 10.0 years [95% CI: 7.6–12.4]; p = 0.008). Multivariate Cox proportional-hazard model results indicated that HLA-G2/6 was an independent prognostic factor for CRC (hazard ratio [HR] = 1.530, 95% CI: 1.125–2.081; p = 0.007). Moreover, HLA-G2/6 expression showed stratified prognostic significance among several CRC patient subgroups, specifically in female patients (p = 0.003), younger patients (<66 years p < 0.001), patients with colon cancer ( p = 0.045), those at stage pT3 ( p = 0.008), pN1 ( p = 0.020), p M0 ( p = 0.009), and AJCC stage III ( p = 0.005). However, no statistical significance was found between HLA-G1/4/5 isoform expression and patient prognosis in CRC.ConclusionsThis is the first study to generate mAbs for the HLA-G2/6 and HLA-G1/4/5 isoforms. Our findings reveal that HLA-G2/6—but not HLA-G1/4/5—expression is an independent prognostic indicator for patients with CRC. In the context of precision medicine, our study also suggests that HLA-G isoform typing may be necessary for HLA-G-targeted cancer immunotherapy. 
651 4 |a United States--US 
651 4 |a Shanghai China 
651 4 |a China 
651 4 |a Zhejiang China 
653 |a Monoclonal antibodies 
653 |a Metastasis 
653 |a Precision medicine 
653 |a Immunotherapy 
653 |a Cancer therapies 
653 |a Leukocytes 
653 |a Isoforms 
653 |a Ethics 
653 |a Peptides 
653 |a Colorectal cancer 
653 |a Colon cancer 
653 |a Clinical significance 
653 |a Cancer immunotherapy 
653 |a Laboratory animals 
653 |a Patients 
653 |a Tissue typing 
653 |a Medical prognosis 
653 |a Cloning 
653 |a Histocompatibility antigen HLA 
653 |a Immune response 
653 |a Immunohistochemistry 
653 |a Hospitals 
653 |a Committees 
653 |a Colorectal carcinoma 
653 |a Antigens 
700 1 |a Qiu-Yue, Han  |u Biological Resource Center, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang, China, Key Laboratory of Human Leukocyte antigen - G (HLA-G) Research &amp; Development of Taizhou, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang, China 
700 1 |a Zhang, Jian-Gang  |u Biological Resource Center, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang, China 
700 1 |a Jiao, Lin  |u Department of Urology, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang, China 
700 1 |a Wei-Hua, Yan  |u Key Laboratory of Human Leukocyte antigen - G (HLA-G) Research &amp; Development of Taizhou, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang, China, Key Laboratory of Minimally Invasive Techniques &amp; Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang, China, Medical Research Center, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang, China 
700 1 |a Lin, Aifen  |u Biological Resource Center, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang, China, Key Laboratory of Human Leukocyte antigen - G (HLA-G) Research &amp; Development of Taizhou, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang, China, Key Laboratory of Minimally Invasive Techniques &amp; Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang, China 
773 0 |t Frontiers in Immunology  |g vol. 16 (Oct 2025), p. 1672144-1672158 
786 0 |d ProQuest  |t Health & Medical Collection 
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