食管癌患者PBMC HLA-A，BmRNA的表达及其研究
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摘要
背景
食管癌是人类常见的消化道肿瘤,占世界恶性肿瘤发病率的第六位。我国是食管癌的高发区,70%的食管癌发生在我国,占恶性肿瘤发病率的第四位。它的特征是早期诊断比较困难且预后差,且男性的发病率是女性的2倍。全世界每年新发食管癌病例约30万。我国食管癌发病率为13/10万,但是食管癌发病隐匿且发病机制尚不明确,确诊时多属中晚期,病灶已经扩散和转移,五年生存率只有10%左右。传统的治疗手段如手术、放疗、化疗等对于晚期食管癌以及转移复发的患者效果不佳。但是,如果在食管癌早期就能诊断的话,通过早期治疗,其五年生存率就可大大提高。由此可见,早期诊断和治疗是食管癌患者长期生存的最佳途径。
人类主要组织相容性抗原系统(MHC)主要表达在白细胞表面称为白细胞抗原系统(HLA),是人类基因组中多态性最高的区域,在人体免疫系统中处于中心地位。肿瘤逃逸宿主的免疫监视重要机制之一是由于肿瘤细胞上人类白细胞抗原(HLA)分子的改变,HLA经典的Ⅰ类分子的主要功能是递呈病毒感染或变异细胞的抗原给细胞毒性T(CTL)细胞,诱导抗病毒或抗肿瘤免疫应答。如果经典HLA-Ⅰ类分子缺失就会导致CTL介导的细胞溶解被阻断,然而,经典的HLA-Ⅰ类分子的缺失又容易导致NK细胞介导的杀伤功能发挥作用。有报道显示:在不同类型的人类肿瘤上,HLA经典的Ⅰ类分子的表达存在不同程度的下调。因此其多态性的研究在科研和临床应用上都具有重要意义。
目的
本研究检测食管癌患者外周血单个核细胞(PBMC)HLA-A和HLA-B mRNA的表达水平,探讨其在肿瘤免疫中的作用及其临床应用价值。
方法
根据GenBank公布的HLA-A,HLA-B基因序列,选取保守区基因设计其特异性引物。收集62例食管癌患者和45名健康体检者外周血单个核细胞,以Beta-actin为内参照,实时荧光RT-PCR方法检测淋巴细胞HLA-A和HLA-B mRNA的表达水平,比较其差异。
结果
食管肿瘤组PBMC的HLA-A和HLA-B mRNA相对表达率分别为0.41±0.26和0.37±0.28;正常对照组分别为1.12±0.54,1.19±0.60;食管肿瘤组HLA-A和HLA-B mRNA相对表达率低于正常对照组,P值均小于0.0001,差异有统计学意义。多因素Logistic回归分析显示HLA-A,B的表达与食管癌的发生有关(P=0.01,P＜0.001)。
结论
食管癌患者外周血淋巴细胞HLA-B mRNA表达状态代表了宿主的免疫状况,HLA-B mRNA的降低或缺失在低分化转移肿瘤更为显著,或许可以成为反映细胞免疫状态的指标之一,对肿瘤的免疫治疗具有指导意义。
HLA-A和HLA-B mRNA的表达水平或许可以作为一个新的肿瘤标志物,对食管癌的早期诊断和治疗提供一个新的思路和方向。
Backgrounds
The esophageal carcinoma is one of common malignant tumors of digestive system.The incidence rate in malignant tumors is situated in sixth in the world.70 percent of esophageal carcinomas were happened in China and the incidence rate is situated in fourth.The features is difficult with early diagnosis and bad prognosis,the male incidence of women are 2 times.Esophageal hair all over the world each year about 300,000 cancer cases.The esophageal cancer incidence rate is ten thousand 13/10 in our country.It can not be diagnosed in early stage,When the symptoms appear,most of the cancer cells have been diffused and metastasesed.The survival rate in five years of esophageal carcinoma hovered at 10 percent all the time.The outcome of esophageal carcinoma is far from satisfaction to the advanced stage with metastasesed and recurred patients by the traditional treatment such as surgery,radiotherapy and chemotherapy.If diagnosed and treated in the early stage,however,the survival rate will be greatly improved.Therefore,the best approach to make the patients with esophageal carcinoma live longer is to diagnose and treat in the early stage.The human major histocompatibility complex(MHC),also called the human leukocyte antigen(HLA),is the most polymorphic region in the whole human genome and plays a key role in the human immune system.Tumor escape from host immunosurveillance is frequently attributed to the alteration of human leukocyte antigen(HLA)-presenting molecules on neoplastic cells.In fact,the major function of HLA class I molecules is to present viral and tumoral antigens to cytotoxic T lymphocyte(CTL),giving rise to the first steps of antiviral or antitumoral immune response.The complete loss of human HLA classI molecules results in a resistance to CTL-mediated lysis,but in turn it renders tumor ceils susceptible to natural killer(NK) cell-mediated killing.HLA class I molecules expression have been reported in different human tumors at variable Frequency,so,the researches on the polymorphism of HLA are very useful for both anthropological studies and clinical medicine.
Aims
To investigate the expression level of HLA-A,B mRNA on Peripheral Blood Mononuclear Cell(PBMC) of esophageal cancer patients and its clinical significance.
Methods
According to HLA-A,HLA-B gene sequence announced in GenBank,select the conservative region of gene to design specific primers. Peripheral blood mononuclear cells HLA-A,B mRNA were detected by real-time reverse quantitative PCR method in 62 patients with Esophageal Cancer and 45 healthy individuals.
Results
The relative expression ratio of PBMC HLA-A,B mRNA was 0.41±0.26,0.37±0.28 in carcinoma group,1.12±0.54,1.19±0.60 in healthy group,respectively.The expression level of HLA-A,B mRNA on PBMC of esophageal cancer group was significantly lower than healthy control group.
Conclusion
The expression of HLA-B mRNA and HLA-B antigen from PBLs in patients with esophageal cancer,especially metastasis of differentiation cancer were lower or lost wholly,leading to default of antigen presentation,the decline of HLA-B mRNA is possible an important mechanism for leading evasion of esophageal cancer from Immunosurveillance.
Results from these data confirm that HLA-A,B play a critical role in the tumor immunity response.HLA-A,B mRNA expression level on PBMC was reduced significantly when tumor occurs.On this ground,it may become an available tumor marker.The data may provide a new method and direction to tumor early diagnosis and treatment.
食管癌是人类常见的消化道肿瘤,占世界恶性肿瘤发病率的第六位。我国是食管癌的高发区,70%的食管癌发生在我国,占恶性肿瘤发病率的第四位。它的特征是早期诊断比较困难且预后差,且男性的发病率是女性的2倍。全世界每年新发食管癌病例约30万。我国食管癌发病率为13/10万,但是食管癌发病隐匿且发病机制尚不明确,确诊时多属中晚期,病灶已经扩散和转移,五年生存率只有10%左右。传统的治疗手段如手术、放疗、化疗等对于晚期食管癌以及转移复发的患者效果不佳。但是,如果在食管癌早期就能诊断的话,通过早期治疗,其五年生存率就可大大提高。由此可见,早期诊断和治疗是食管癌患者长期生存的最佳途径。
人类主要组织相容性抗原系统(MHC)主要表达在白细胞表面称为白细胞抗原系统(HLA),是人类基因组中多态性最高的区域,在人体免疫系统中处于中心地位。肿瘤逃逸宿主的免疫监视重要机制之一是由于肿瘤细胞上人类白细胞抗原(HLA)分子的改变,HLA经典的Ⅰ类分子的主要功能是递呈病毒感染或变异细胞的抗原给细胞毒性T(CTL)细胞,诱导抗病毒或抗肿瘤免疫应答。如果经典HLA-Ⅰ类分子缺失就会导致CTL介导的细胞溶解被阻断,然而,经典的HLA-Ⅰ类分子的缺失又容易导致NK细胞介导的杀伤功能发挥作用。有报道显示:在不同类型的人类肿瘤上,HLA经典的Ⅰ类分子的表达存在不同程度的下调。因此其多态性的研究在科研和临床应用上都具有重要意义。
目的
本研究检测食管癌患者外周血单个核细胞(PBMC)HLA-A和HLA-B mRNA的表达水平,探讨其在肿瘤免疫中的作用及其临床应用价值。
方法
根据GenBank公布的HLA-A,HLA-B基因序列,选取保守区基因设计其特异性引物。收集62例食管癌患者和45名健康体检者外周血单个核细胞,以Beta-actin为内参照,实时荧光RT-PCR方法检测淋巴细胞HLA-A和HLA-B mRNA的表达水平,比较其差异。
结果
食管肿瘤组PBMC的HLA-A和HLA-B mRNA相对表达率分别为0.41±0.26和0.37±0.28;正常对照组分别为1.12±0.54,1.19±0.60;食管肿瘤组HLA-A和HLA-B mRNA相对表达率低于正常对照组,P值均小于0.0001,差异有统计学意义。多因素Logistic回归分析显示HLA-A,B的表达与食管癌的发生有关(P=0.01,P＜0.001)。
结论
食管癌患者外周血淋巴细胞HLA-B mRNA表达状态代表了宿主的免疫状况,HLA-B mRNA的降低或缺失在低分化转移肿瘤更为显著,或许可以成为反映细胞免疫状态的指标之一,对肿瘤的免疫治疗具有指导意义。
HLA-A和HLA-B mRNA的表达水平或许可以作为一个新的肿瘤标志物,对食管癌的早期诊断和治疗提供一个新的思路和方向。
Backgrounds
The esophageal carcinoma is one of common malignant tumors of digestive system.The incidence rate in malignant tumors is situated in sixth in the world.70 percent of esophageal carcinomas were happened in China and the incidence rate is situated in fourth.The features is difficult with early diagnosis and bad prognosis,the male incidence of women are 2 times.Esophageal hair all over the world each year about 300,000 cancer cases.The esophageal cancer incidence rate is ten thousand 13/10 in our country.It can not be diagnosed in early stage,When the symptoms appear,most of the cancer cells have been diffused and metastasesed.The survival rate in five years of esophageal carcinoma hovered at 10 percent all the time.The outcome of esophageal carcinoma is far from satisfaction to the advanced stage with metastasesed and recurred patients by the traditional treatment such as surgery,radiotherapy and chemotherapy.If diagnosed and treated in the early stage,however,the survival rate will be greatly improved.Therefore,the best approach to make the patients with esophageal carcinoma live longer is to diagnose and treat in the early stage.The human major histocompatibility complex(MHC),also called the human leukocyte antigen(HLA),is the most polymorphic region in the whole human genome and plays a key role in the human immune system.Tumor escape from host immunosurveillance is frequently attributed to the alteration of human leukocyte antigen(HLA)-presenting molecules on neoplastic cells.In fact,the major function of HLA class I molecules is to present viral and tumoral antigens to cytotoxic T lymphocyte(CTL),giving rise to the first steps of antiviral or antitumoral immune response.The complete loss of human HLA classI molecules results in a resistance to CTL-mediated lysis,but in turn it renders tumor ceils susceptible to natural killer(NK) cell-mediated killing.HLA class I molecules expression have been reported in different human tumors at variable Frequency,so,the researches on the polymorphism of HLA are very useful for both anthropological studies and clinical medicine.
Aims
To investigate the expression level of HLA-A,B mRNA on Peripheral Blood Mononuclear Cell(PBMC) of esophageal cancer patients and its clinical significance.
Methods
According to HLA-A,HLA-B gene sequence announced in GenBank,select the conservative region of gene to design specific primers. Peripheral blood mononuclear cells HLA-A,B mRNA were detected by real-time reverse quantitative PCR method in 62 patients with Esophageal Cancer and 45 healthy individuals.
Results
The relative expression ratio of PBMC HLA-A,B mRNA was 0.41±0.26,0.37±0.28 in carcinoma group,1.12±0.54,1.19±0.60 in healthy group,respectively.The expression level of HLA-A,B mRNA on PBMC of esophageal cancer group was significantly lower than healthy control group.
Conclusion
The expression of HLA-B mRNA and HLA-B antigen from PBLs in patients with esophageal cancer,especially metastasis of differentiation cancer were lower or lost wholly,leading to default of antigen presentation,the decline of HLA-B mRNA is possible an important mechanism for leading evasion of esophageal cancer from Immunosurveillance.
Results from these data confirm that HLA-A,B play a critical role in the tumor immunity response.HLA-A,B mRNA expression level on PBMC was reduced significantly when tumor occurs.On this ground,it may become an available tumor marker.The data may provide a new method and direction to tumor early diagnosis and treatment.
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