Background: Human leukocyte antigen G (HLA-G) is an immune checkpoint molecule with immunosuppressive and anti-inflammatory activities. It belongs to class I non-classical major histocompatibility complex molecules and has been upregulated in various cancer types. In bladder cancer (BC) tumors, the association of HLA-G with cancer progression has to be explained. Methods: A total of 89 BC patients and 74 control subjects were genotyped for the HLA-G 14 bp ins/del polymorphism. In urine cell samples, HLA-G mRNA expression was analyzed using real-time PCR. Soluble HLA-G (sHLA-G) serum levels were measured by ELISA. The associations between the HLA-G 14 bp ins/del polymorphism, HLA-G mRNA expression, and/or sHLA-G levels and selected variables including tumor grade, disease stage, body mass index, and heart rate variability (HRV) parameters were evaluated. Results: The protective HLA-G 14 bp ins/ins genotype under the recessive genetic model was associated with lower HLA-G mRNA expression in the BC group (p= 0.049). Significantly higher HLA-G mRNA expression was detected in patients with pT2 + pT3 as compared to those with pTa + pT1 stages (p= 0.0436). Furthermore, higher HLA-G mRNA expression was observed in high-grade muscle-infiltrating BC (MIBC) than in the low-grade non-MIBC group (p= 0.0365). Patients with a level of sHLA-G above 29 U/mL had shorter disease-free survival than patients with lower sHLA-G levels. Furthermore, the opposite HRV correlations with sHLA-G levels in BC patients as compared to controls probably reflect the different roles of HLA-G in health and cancer. Conclusions: Our results suggest the impact of the HLA-G 14 bp ins/del variant, HLA-G expression, and autonomic nervous system imbalance on advanced stages of BC.
背景：人类白细胞抗原G（HLA-G）是一种具有免疫抑制和抗炎活性的免疫检查点分子，属于I类非经典主要组织相容性复合体分子，在多种癌症类型中表达上调。在膀胱癌（BC）肿瘤中，HLA-G与癌症进展的关联尚需阐明。 方法：对89例BC患者和74例对照受试者进行HLA-G 14 bp插入/缺失多态性基因分型。采用实时荧光定量PCR分析尿液细胞样本中的HLA-G mRNA表达水平，并通过ELISA检测可溶性HLA-G（sHLA-G）血清浓度。评估HLA-G 14 bp插入/缺失多态性、HLA-G mRNA表达及/或sHLA-G水平与肿瘤分级、疾病分期、体重指数及心率变异性（HRV）参数等选定变量之间的关联。 结果：在隐性遗传模型下，具有保护作用的HLA-G 14 bp插入/纯合基因型与BC组较低的HLA-G mRNA表达相关（p=0.049）。与pTa + pT1分期患者相比，pT2 + pT3分期患者的HLA-G mRNA表达显著更高（p=0.0436）。此外，高级别肌层浸润性膀胱癌（MIBC）组的HLA-G mRNA表达高于低级别非MIBC组（p=0.0365）。sHLA-G水平高于29 U/mL的患者较低水平患者的无病生存期更短。值得注意的是，与对照组相比，BC患者中HRV参数与sHLA-G水平呈现相反的关联模式，这可能反映了HLA-G在健康状态和癌症中具有不同作用。 结论：本研究结果表明HLA-G 14 bp插入/缺失变异、HLA-G表达及自主神经系统失衡对膀胱癌晚期进展具有影响。
肿瘤(癌症)患者之家