Wang X C, Zhang J Q, Shen Y Q, Miao F Q, Xie W
State Education Ministry Laboratory of Developmental Genes and Human Diseases, Jiangsu Provincial Key Laboratory of Gene Diagnosis and Therapy, Genetics Research Center, Southeast University Medical School, Nanjing, China.
J Exp Clin Cancer Res. 2006 Mar;25(1):115-9.
Human major histocompatibility complex (HLA), located on 6p21.3, encodes for genes involved in antigen processing and presentation. Loss of heterozygosity (LOH) at 6p21.3 may cause downregulated expression of HLA, thus provide tumor cells with an immune-escape tumor phenotype. In the present study, we detected HLA class I expression in gastric cancer and correlated it with LOH at 6p21.3. The expression of HLA class I antigen was analyzed by immunohistochemical procedure in 50 fresh surgically removed gastric cancers and corresponding normal tissues using 5 monoclonal antibodies (mAbs). LOH studies were detected by using 6 microsatellite markers located at 6p21.3, 1 marker located at 6q21 and 2 microsatellite markers flanking the beta2m gene. HLA class I complex was obviously downregulated in gastric cancer compared with corresponding normal tissues (t=4.00, p<0.01). The expression of beta2m gene was also downregulated in tumor, but not concordant with HLA class I surface downregulation. Out of the 50 tumors, 25 (50%) showed LOH of at least one STR marker at 6p21.3 while only 11 (22%) showed LOH of the two markers flanking the beta2m gene. The LOH frequency of D6S105, which is close to HLA-A gene, was the highest in all STR markers studied (34%). Downregulation of HLA class I expression was correlated with loss of chromosomal regions at 6p21.3 (chi-squared = 5.13, p<0.05). Our results suggested that LOH of 6p21.3 contributed to HLA class I downregulated expression in gastric cancer especially at HLA-A locus. LOH of HLA-A gene might be one of the mechanisms underlying the abnormal expression of HLA class I complex.
人类主要组织相容性复合体（HLA）位于6号染色体短臂21.3区，编码参与抗原加工和呈递的基因。6号染色体短臂21.3区杂合性缺失（LOH）可能导致HLA表达下调，从而赋予肿瘤细胞免疫逃逸的肿瘤表型。在本研究中，我们检测了胃癌中HLA I类分子的表达，并将其与6号染色体短臂21.3区的杂合性缺失相关联。采用免疫组化方法，使用5种单克隆抗体（mAb）对50例手术切除的新鲜胃癌组织及相应正常组织进行HLA I类抗原表达分析。通过使用位于6号染色体短臂21.3区的6个微卫星标记、位于6号染色体长臂21区的1个标记以及β2微球蛋白（β2m）基因两侧的2个微卫星标记进行杂合性缺失研究。与相应正常组织相比，胃癌中HLA I类复合体明显下调（t = 4.00，p < 0.01）。肿瘤组织中β2m基因的表达也下调，但与HLA I类分子表面下调不一致。在50例肿瘤中，25例（50%）在6号染色体短臂21.3区至少有一个STR标记出现杂合性缺失，而只有11例（22%）β2m基因两侧的两个标记出现杂合性缺失。在所有研究的STR标记中，靠近HLA - A基因的D6S105杂合性缺失频率最高（34%）。HLA I类分子表达下调与6号染色体短臂21.3区染色体区域缺失相关（卡方检验 = 5.13，p < 0.05）。我们的结果表明，6号染色体短臂21.3区的杂合性缺失导致胃癌中HLA I类分子表达下调，尤其是在HLA - A位点。HLA - A基因的杂合性缺失可能是HLA I类复合体异常表达的潜在机制之一。
