Zemni Ines, Bortolotti Daria, Dhouioui Sabrine, Baroudi Sana, Ferjani Malek, Nasri Inès, Zenzri Yosr, Rahman Md Ataur, Harrath Abdel Halim, Rizzo Roberta, Boujelbene Nadia, Zidi Inès
Laboratory of Microorganisms and Active Biomolecules (LR03ES03), Sciences Faculty of Tunis, University of Tunis El Manar, Tunis, Tunisia; Department of Surgical Oncology, Salah Azaiez Institute, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia.
Department of Chemical, Pharmaceutical and Agricultural Science, University of Ferrara, Ferrara, Italy.
Immunobiology. 2025 Jan;230(1):152864. doi: 10.1016/j.imbio.2024.152864. Epub 2024 Dec 15.
Gastric cancer (GC) remains a serious health concern and is characterized by a multifactorial etiology involving both genetic and epigenetic factors. The aim of the current study was to examine the relationship between Human leukocyte antigen (HLA)-G 3'UTR polymorphisms and the expression of HLA-G in both tumor tissues and plasma samples from patients with GC in the Tunisian population.
HLA-G 3'UTR polymorphisms (14pb Insertion/deletion and + 3142C/G) were identified by polymerase chain reaction (PCR) or Sanger sequencing. Plasma levels of sHLA-G (total sHLA-G, shed HLA-G1 and HLA-G5) were determined. Immunohistochemistry was used to evaluate the expression of HLA-G in tumor tissues.
The Del/Del genotype and Del allele frequencies were different between GC patients and healthy donors (HD) (OR [95 % CI] = 2.483 [1.070-5.410], p = 0.025 vs. OR [95 % CI] = 1.537 [0.924-2.584], p = 0.099; respectively). The C/C genotype and C allele frequencies were significantly greater in GC patients than in HD (OR [95 % CI] = 2.269[0.1.070-4.904], p = 0.033 vs. OR [95 % CI] = 1.746[1.045-2.878], p = 0.034; respectively). Interestingly, the Del/Del genotype and Del allele were significantly associated with an increased risk of GC in patients aged ≥55 years at diagnosis. HLA-G was highly expressed in GC tissues, particularly in tissues with advanced tumor invasion (T3 + T4). Compared with HD, GC patients had higher soluble HLA-G, shed HLA-G1 and HLA-G5 levels (Mann-Whitney: p = 0.001, p = 0.001 and p = 0.643, respectively). Assessment of patients' survival by Kaplan-Meier analysis indicated that the Del allele was significantly associated with reduced overall survival (OS) in GC patients at advanced stages III + IV (p = 0.043).
These results suggest that HLA-G 3'UTR polymorphisms are associated with GC susceptibility in Tunisian population. The expression of HLA-G in both the tissue and plasma may play an important role in the development and progression of GC. Therefore, the current study supported the recommendation of investigating HLA-G 3'UTR polymorphisms in GC and indicated that HLA-G molecules could serve as promising therapeutic targets in GC.
胃癌（GC）仍然是一个严重的健康问题，其病因是多因素的，涉及遗传和表观遗传因素。本研究的目的是探讨突尼斯人群中胃癌患者肿瘤组织和血浆样本中人类白细胞抗原（HLA）-G 3'非翻译区（UTR）多态性与HLA-G表达之间的关系。
通过聚合酶链反应（PCR）或桑格测序鉴定HLA-G 3'UTR多态性（14pb插入/缺失和+3142C/G）。测定血浆中可溶性HLA-G（总可溶性HLA-G、可溶性HLA-G1和HLA-G5）水平。采用免疫组织化学法评估肿瘤组织中HLA-G的表达。
GC患者与健康供体（HD）的Del/Del基因型和Del等位基因频率不同（OR [95%CI]=2.483 [1.070 - 5.410]，p = 0.025；OR [95%CI]=1.537 [0.924 - 2.584]，p = 0.099）。GC患者的C/C基因型和C等位基因频率显著高于HD（OR [95%CI]=2.269[0.1.070 - 4.904]，p = 0.033；OR [95%CI]=1.746[1.045 - 2.878]，p = 0.034）。有趣的是，Del/Del基因型和Del等位基因与诊断时年龄≥55岁的患者患GC的风险增加显著相关。HLA-G在GC组织中高表达，尤其是在肿瘤浸润晚期（T3 + T4）的组织中。与HD相比，GC患者的可溶性HLA-G、可溶性HLA-G1和HLA-G5水平更高（曼-惠特尼检验：p = 0.001、p = 0.001和p = 0.643）。通过Kaplan-Meier分析评估患者生存率表明，Del等位基因与晚期III + IV期GC患者的总生存期（OS）显著降低相关（p = 0.043）。
这些结果表明，HLA-G 3'UTR多态性与突尼斯人群的GC易感性相关。HLA-G在组织和血浆中的表达可能在GC的发生和发展中起重要作用。因此，本研究支持在GC中研究HLA-G 3'UTR多态性的建议，并表明HLA-G分子可能是GC中有前景的治疗靶点。
