非小细胞肺癌患者外周静脉血、口腔粘膜细胞MT-1A、2A、3、4 mRNA的表达及临床意义
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摘要
目的：研究金属硫蛋白(MT)1A、2A、3、4 mRNA在非小细胞肺癌患者外周静脉血及口腔粘膜的表达情况,探讨其作为肺癌分子生物学标志物的可行性。方法：分别选取30例非小细胞肺癌及30例肺良性肿瘤患者作为实验组,将其分为鳞癌组、腺癌组、结核球组及炎性假瘤组,30例非小细胞肺癌根据转移情况分为：转移组和未转移组,12例肺裂伤患者作为正常对照组,利用RT-PCR方法检测所选患者外周静脉血、口腔粘膜细胞中MT-1A、2A、3、4 mRNA的表达情况,免疫组化方法检测肺肿瘤组织及瘤旁组织MT的表达情况；对比分析非小细胞肺癌患者MT在基因、蛋白水平的表达情况。结果：1.在血液中,与正常对照组比较,血液中各肿瘤组MT-1A、2A、4 mRNA的表达均下降。’鳞癌组的MT-1A、2A mRNA下调显著,差异具有统计学意义(P<0.01); MT-4 mRNA的表达下调亦有统计学意义(P<0.05)；未转移组的MT-1A、2A、4 mRNA(P<0.01),转移组MT-1A mRNA表达显著下调(P<0.05)；与转移组相比,未转移组MT-1A、2A mRNA表达下调显著(P<0.05),其余组表达变化无统计学意义。2.在口腔粘膜细胞中,与正常对照组比较,各肿瘤组MT-1A、2A、3、4 mRNA在口腔粘膜细胞中的表达均上调,除鳞癌组MT-4 mRNA外,其余各组差异均有统计学意义：结核球组MT-2A、4 mRNA及炎性假瘤组MT-2A mRNA P<0.05,其他P<0.01；与鳞癌组相比,结核球组MT-2A mRNA表达上调(P<0.05)；其余组表达变化无统计学意义。3.在肺组织中,分别以正常对照组、自身瘤旁组作为对照进行对比分析：①.与正常对照组相比较,鳞癌组的瘤体组织MT-1A、2A mRNA表达上调,腺癌的瘤体组MT-3mRNA表达上调,炎性假瘤的瘤体组MT-1A mRNA表达上调,差异性具有统计学意义(P<0.05)。②.与自身瘤旁组织相比,鳞癌的瘤体组MT-2A mRNA表达增强,腺癌的瘤体组MT-3 mRNA表达增强,炎性假瘤的瘤体组MT-1A mRNA表达增强,差异性具有统计学意义(P<0.05)。与正常对照组相比,未转移组MT-3 mRNA表达无显著变化,转移组MT-3mRNA表达显著上调(P<0.05)；与未转移组相比,转移组MT-3 mRNA表达显著上调(P<0.05)。4.采用免疫组化方法对肺组织内MT蛋白水平的表达进行测定,发现与正常对照组相比,鳞癌及腺癌瘤体组表达增高,差异性有统计学意义(P<0.01),炎性假瘤瘤体组增高有统计学意义(P<0.05)；与自身瘤旁组相比,鳞癌、腺癌及炎性假瘤瘤体组表达增高明显,差异性有统计学意义(腺癌组P>0.01,鳞癌、炎性假瘤组P<0.05)；与正常对照组相比,转移组增高显著,差异性具有统计学意义(P<0.01),未转移组增高亦具有统计学意义(P<0.05);与未转移组相比,转移组增高具有统计学意义(P<0.05)。结论：血液中MT-1A mRNA有望成为鳞状细胞肺癌及其转移的辅助诊断标志物之一；口腔粘膜细胞中MT-2A mRNA有望成为鳞状细胞肺癌与结核球的辅助鉴别诊断标志物之一；肺组织中MT-3 mRNA表达增强,可能提示肿瘤组织的侵袭性较强。
Objective:To study Metallothionein(MT) 1A,2A,3,4-mRNA expressions in the peripheral blood and bucall cell of patients with non-small cell lung cancer and the clinical utility as molecular markers.Methods:30 cases with non-small cell lung cancer and 30 cases with benign lung tumor are selected as the research objects,including squamous cell cancer group, adenocarci-noma group,tuberculma group and inflammatory pseudotumor group.30 cases with non-small cell lung cancer are divided into two groups according to metastatic condition,including metastases group(17 cases) and no metastases group(13 cases).12 cases with lung laceration are selected as normal controls.MT1A,2A,3,4-mRNA expressions in the peripheral blood,bucall cell and lung tissue of all the cases are detected by RT-PCR.MT expressions in the lung tumor tissue and tumor surrounding tissue are deceted by immunohistochemistry. Comparative analyses of MT expressions at the mRNA and protein level are performed.Results:(1) MT-1A,2A,4 mRNA expressions in the peripheral blood of lung tumor group are down-regulated compared with those of normal control group.MT-1A,2A,4 mRNA expressions of squamous cell cancer group are significantly decreased compared with those of normal control group.MT-1A,2A,4 mRNA expressions of metastases group and MT-1A mRNA expression of no metastases group are down-regulated compared with those of normal control group.Compared with MT-1A,2A mRNA expressions of metastases group,those of no metastases goup are significantly decreased(P<0.05).Expressions change of the other groups else has no statistical significance.(2) MT-1A,2A,3,4 mRNA expressions in bucall cell of all the tumor group are up-regulated compared with those of normal control group.Each group has a significant change except for MT-4 mRNA of squamous cell cancer group compared with normal control group.MT-2A mRNA expression of tuberculoma group is significantly increased compared with that of squamous cell cancer group.There is no significant difference in other groups.(3) Normal group and tumor surrounding group as control groups are performed respectively in the lung tissue.①MT-1A,2A mRNA expressions of squamous cell cancer's tumor group are significantly increased compared with those of normal control group(P<0.05),and MT-3 mRNA expression of adenocarcinoma's tumor group and MT-1A mRNA expression of inflammatory pseudotumor's tumor group are also significantly increased (P<0.05).②MT-2A mRNA expression of tumor group is significantly increased compared with that of tumor surrounding group in squamous cell cancer (P<0.05).MT-3 mRNA expression in tumor group of adenocarcinoma and MT-1A mRNA expression in tumor group of inflammatory pseudotumor are also significantly increased compared with those in tumor surrounding of their own (P<0.05).MT-3 mRNA expression of no metastases group had no significant change compared with that of normal contral group,while MT-3 mRNA expression of metastases group has a significant up-regulation (P<0.05).MT-3 mRNA expression of metastases group is significant increased compared with that of no metastases group(P<0.05).(4) MT expression of protein level in lung tissue is measured by immunohistochemical,and find that squamous cell cancer group and adenocarcinoma group are significantly increased compared with normal control group(P<0.01).Inflammatory pseudotumor group is also significantly increased compared with normal control group (P<0.05).squamous cell cancer group and adenocarcinoma group are significantly increased compared with their own tumor surrounding groups(adenocarcinoma group P<0.01,squamous cell cancer group and inflam matory pseudotumor group P<0.05).Compared with normal control group,metastases group and no metastases group are significantly inceased(metastases group P<0.01,no metastases group P<0.05).MT expression of metastases group is higher than that of no metastases group(P<0.05). Conclusions:MT-1 A mRNA in blood is expected to become an auxiliary diagnostic and metastatic marker of squamous cell lung cancer.MT-2A mRNA in bucall cell is expected to become an auxiliary diagnostic marker to distinguish squamous cell lung cancer from tuberculma.In lung tissue,up-regulation of MT-3 mRNA expression may be a sign of strong invasiveness.
Objective:To study Metallothionein(MT) 1A,2A,3,4-mRNA expressions in the peripheral blood and bucall cell of patients with non-small cell lung cancer and the clinical utility as molecular markers.Methods:30 cases with non-small cell lung cancer and 30 cases with benign lung tumor are selected as the research objects,including squamous cell cancer group, adenocarci-noma group,tuberculma group and inflammatory pseudotumor group.30 cases with non-small cell lung cancer are divided into two groups according to metastatic condition,including metastases group(17 cases) and no metastases group(13 cases).12 cases with lung laceration are selected as normal controls.MT1A,2A,3,4-mRNA expressions in the peripheral blood,bucall cell and lung tissue of all the cases are detected by RT-PCR.MT expressions in the lung tumor tissue and tumor surrounding tissue are deceted by immunohistochemistry. Comparative analyses of MT expressions at the mRNA and protein level are performed.Results:(1) MT-1A,2A,4 mRNA expressions in the peripheral blood of lung tumor group are down-regulated compared with those of normal control group.MT-1A,2A,4 mRNA expressions of squamous cell cancer group are significantly decreased compared with those of normal control group.MT-1A,2A,4 mRNA expressions of metastases group and MT-1A mRNA expression of no metastases group are down-regulated compared with those of normal control group.Compared with MT-1A,2A mRNA expressions of metastases group,those of no metastases goup are significantly decreased(P<0.05).Expressions change of the other groups else has no statistical significance.(2) MT-1A,2A,3,4 mRNA expressions in bucall cell of all the tumor group are up-regulated compared with those of normal control group.Each group has a significant change except for MT-4 mRNA of squamous cell cancer group compared with normal control group.MT-2A mRNA expression of tuberculoma group is significantly increased compared with that of squamous cell cancer group.There is no significant difference in other groups.(3) Normal group and tumor surrounding group as control groups are performed respectively in the lung tissue.①MT-1A,2A mRNA expressions of squamous cell cancer's tumor group are significantly increased compared with those of normal control group(P<0.05),and MT-3 mRNA expression of adenocarcinoma's tumor group and MT-1A mRNA expression of inflammatory pseudotumor's tumor group are also significantly increased (P<0.05).②MT-2A mRNA expression of tumor group is significantly increased compared with that of tumor surrounding group in squamous cell cancer (P<0.05).MT-3 mRNA expression in tumor group of adenocarcinoma and MT-1A mRNA expression in tumor group of inflammatory pseudotumor are also significantly increased compared with those in tumor surrounding of their own (P<0.05).MT-3 mRNA expression of no metastases group had no significant change compared with that of normal contral group,while MT-3 mRNA expression of metastases group has a significant up-regulation (P<0.05).MT-3 mRNA expression of metastases group is significant increased compared with that of no metastases group(P<0.05).(4) MT expression of protein level in lung tissue is measured by immunohistochemical,and find that squamous cell cancer group and adenocarcinoma group are significantly increased compared with normal control group(P<0.01).Inflammatory pseudotumor group is also significantly increased compared with normal control group (P<0.05).squamous cell cancer group and adenocarcinoma group are significantly increased compared with their own tumor surrounding groups(adenocarcinoma group P<0.01,squamous cell cancer group and inflam matory pseudotumor group P<0.05).Compared with normal control group,metastases group and no metastases group are significantly inceased(metastases group P<0.01,no metastases group P<0.05).MT expression of metastases group is higher than that of no metastases group(P<0.05). Conclusions:MT-1 A mRNA in blood is expected to become an auxiliary diagnostic and metastatic marker of squamous cell lung cancer.MT-2A mRNA in bucall cell is expected to become an auxiliary diagnostic marker to distinguish squamous cell lung cancer from tuberculma.In lung tissue,up-regulation of MT-3 mRNA expression may be a sign of strong invasiveness.
引文
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3.胡颖,廖美琳,丁嘉安等MT1/P16和MT2/P15基因共丢失与原发性非小细胞肺癌预后的研究[J].肿瘤,2001,21(6):443-5.
4. Dziegiel P,Jelen M,Muszczynska B,et al.Role of metallothionein expression in non-small cell lung carcinomas[J].Rocz Akad Med Bialymst,2004,49(1):43-45.
5.卢铀,毕锋,李平.临床肿瘤学[M].成都：四川大学出版社,2009,3:2.
6.丁艳,郭海,顾武军.白细胞免疫在肿瘤研究中的进展[J].辽宁大学学报,2007,9(1):68-69.
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