CAJ | 학술논문

背景与目的：作为重要的表观遗传学现象之一，DNA甲基化对基因表达发挥着重要的调控功能。研究表明肿瘤细胞基因组正常DNA甲基化模式异常改变所导致的肿瘤相关基因功能异常可能参与肿瘤发生与发展。本研究通过检测食管鳞状细胞癌(esophageal squamous cell carcinomas，ESCC)组织中质膜微囊蛋白-1(caveolin-1，CAV-1)基因的表达及甲基化状态，探讨CAV-1基因在食管鳞癌发生及发展中的作用。方法：分别应用甲基化特异性PCR(MSP)、RT-PCR法、免疫组织化学SP法检测食管癌及相应癌旁正常黏膜组织标本中CAV-1基因甲基化状态、mRNA及蛋白表达情况。结果：CAV-1 mRNA在食管癌和癌旁正常组织中的表达量分别为0.86±0.56和0.40±0.36，食管癌组织中CAV-1 mRNA表达量明显高于癌旁正常组织，2者差异有统计学意义(P<0.05)。CAV-1 mRNA表达与患者的淋巴结转移及肿瘤组织学分级有关(P<0.05)；食管鳞癌组织中，CAV-1蛋白表达阳性率为66.7%(34/51)；显著高于正常食管黏膜组织(15.7%，8/51)(P<0.01)。CAV-1蛋白表达与患者的淋巴结转移有关(P<0.05)，而与肿瘤的临床分期和分化程度无关(P>0.05)。51例食管癌组织中1例发生了基因启动子区甲基化，甲基化率为2.0%(1/51)；而相应癌旁正常黏膜组织中未发现有该基因的甲基化现象。食管癌组织中该基因的甲基化率与相应癌旁正常组织相比，差异无统计学意义(P>0.05)。结论：CAV-1基因在食管鳞癌组织中mRNA及蛋白表达均明显高于癌旁正常黏膜组织，该基因的高表达对于肿瘤的发生及淋巴结的转移起到了一定的促进作用；癌及癌旁组织中该基因的表达异常均与该基因的甲基化状态无关。
배경여목적：작위중요적표관유전학현상지일，DNA갑기화대기인표체발휘착중요적조공공능。연구표명종류세포기인조정상DNA갑기화모식이상개변소도치적종류상관기인공능이상가능삼여종류발생여발전。본연구통과검측식관린상세포암(esophageal squamous cell carcinomas，ESCC)조직중질막미낭단백-1(caveolin-1，CAV-1)기인적표체급갑기화상태，탐토CAV-1기인재식관린암발생급발전중적작용。방법：분별응용갑기화특이성PCR(MSP)、RT-PCR법、면역조직화학SP법검측식관암급상응암방정상점막조직표본중CAV-1기인갑기화상태、mRNA급단백표체정황。결과：CAV-1 mRNA재식관암화암방정상조직중적표체량분별위0.86±0.56화0.40±0.36，식관암조직중CAV-1 mRNA표체량명현고우암방정상조직，2자차이유통계학의의(P<0.05)。CAV-1 mRNA표체여환자적림파결전이급종류조직학분급유관(P<0.05)；식관린암조직중，CAV-1단백표체양성솔위66.7%(34/51)；현저고우정상식관점막조직(15.7%，8/51)(P<0.01)。CAV-1단백표체여환자적림파결전이유관(P<0.05)，이여종류적림상분기화분화정도무관(P>0.05)。51례식관암조직중1례발생료기인계동자구갑기화，갑기화솔위2.0%(1/51)；이상응암방정상점막조직중미발현유해기인적갑기화현상。식관암조직중해기인적갑기화솔여상응암방정상조직상비，차이무통계학의의(P>0.05)。결론：CAV-1기인재식관린암조직중mRNA급단백표체균명현고우암방정상점막조직，해기인적고표체대우종류적발생급림파결적전이기도료일정적촉진작용；암급암방조직중해기인적표체이상균여해기인적갑기화상태무관。
Background and purpose: As one of the important epigenetic phenomena, DNA methylation plays an important regulatory function for the expression of genes. Study shows that abnormal changes of DNA methy-lation patterns of normal tumor cell genome leads to dysfunction of cancer related gene, and this may be associated with tumor occurrence and development. The study investigated the promoter methylation and expression of caveolin-1 (CAV-1) gene in esophageal squamous cell carcinoma (ESCC), and to elucidate its role in ESCC. Methods:We used MSP approach, RT-PCR, and immunohistochemistry method respectively to examine the methylation status of the 5’CpG island of CAV-1 gene and its expression at mRNA and protein levels in tumors and corresponding normal tissues. Results: CAV-1 mRNA expression in tumor tissues (0.86±0.56) was signiifcantly higher than that in corresponding normal tissues (0.40±0.36, P<0.05). The mRNA expression of CAV-1 was correlated with status of lymphatic metastasis and TNM stage of ESCC patients (P<0.05). The protein expression of CAV-1 in tumor specimens (66.7%, 34/51) was signiifcantly higher than that in corresponding normal tissues (15.7%, 8/51, P<0.01). The protein expression of CAV-1 was signiifcantly associated with lymphatic metastasis of ESCC (P<0.05), however, it was not associated with differen-tiation and TNM stage (P>0.05). The promoter methylation frequency of CAV-1 in tumor specimens was 2.0%(1/51), and the methylation phenomenon has not been found in corresponding normal tissues. The promoter methylation fre-quency of CAV-1 in tumor specimens showed no signiifcant difference compared with the corresponding normal tissues (P>0.05). Conclusion:The mRNA and protein expression of CAV-1 in tumor specimens was signiifcantly higher than that in corresponding normal tissues. Aberrant high expression of CAV-1 has played a certain role in promoting tumori-genesis and lymph node metastasis. The expression both in ESCC and corresponding normal tissues has no correlation with the promoter methylation status.