TSLC1和DAL-1/4.1B在胰腺癌中的表达及其临床意义

目的:探讨TSLC1和DAL-1/4.1B两种蛋白在胰腺癌中的表达和临床病理意义.方法:采用免疫组织化学S-P法检测42例胰腺癌组织、11例胰腺炎组织和9例正常胰腺组织中TSLC1和DAL-1/4.1B两种蛋白的表达.结果:TSLC1、DAL-1/4.1B蛋白在胰腺癌组织中的阳性表达率均明显低于在正常胰腺组织和胰腺炎组织中的表达(30.95%vs77.78%,81.82%;28.57% vs 66.67%,81.82%,P<0.05或0.01).TSLC1和DAL-1/4.1B蛋白的异常表达均与胰腺癌的分化程度、淋巴结转移和TNM分期相关(P<0.05),而与患者的性别、年龄、部位和病理分型无关.在42例胰腺癌中TSLC1与DAL-1/4.1B蛋白表达呈显著正相关(rs=0.489,P<0.01).结论:胰腺癌中存在TSLC1和DAL-1/4.1B基因的失活和蛋白表达下调,二者可能通过TSLC1-DAL-1/4.1B级联反应共同参与胰腺癌的发生、发展和转移.

TSLC1、DAL-1/4.1B和MPP3在大肠癌中的表达及其临床意义

目的:研究肺癌肿瘤抑制物1(tumor suppressor i n lung cancer-1,TSLC1)、肺腺癌差异表达因子4.1B(differentially expressed in adenocarcinoma of the lung/4.1B,DAL-1/4.1B)和果蝇肿瘤抑制因子同源分子-3(membraneprotein palmitoylated 3,MPP3)在大肠癌中的表达及其相互关系,并探讨其临床病理意义.方法:采用免疫组织化学EnVisionTM法检测76例大肠癌和22例正常肠黏膜组织中TSLC1、DAL-1/4.1B、MPP3的表达,并结合其临床病理特征分析.结果:正常肠黏膜组织中TSLC1、DAL-1/4.1B和MPP3均呈清晰的棕黄色染色定位在上皮细胞质和/或细胞膜.TSLC1、DAL-1/4.1B和MPP3蛋白在大肠癌中的阳性表达率均明显低于其在正常肠黏膜组织中的表达(32.89%vs81.81%,27.63%vs 63.64%,35.53%vs 68.18%;P<0.05).TSLC1、DAL-1/4.1B和MPP3蛋白在大肠癌的表达缺失与肿瘤的分化程度、浸润深度、淋巴结转移和Dukes'分期密切相关(P<0.05),而与患者的性别、年龄和肿瘤大小无关.结论:大肠癌中存在TSLC1、DAL-1/4.1B和MPP3基因的表达缺失,TSLC1与DAL-1/4.1B及MPP3之间的相互作用可能是其发挥肿瘤抑制作用的主要分子机制,三者可能通过TSLC1级联反应共同参与大肠癌的发生、发展和转移.

新抑癌基因——TSLC1和DAL-1／4．1B与恶性肿瘤的关系

肺癌肿瘤抑制物基因1（tumor suppressor of non—small cell lung cancer1／TSLC1）和肺腺癌差异表达因子4．1B（differentially expressed in adenocarcinoma of the lung／4．1B，DAL-1／4．1B）均是近年新发现的抑癌基因，具有潜在的肿瘤抑制作用。研究表明二者在多种组织中都有表达，而且在许多肿瘤中均表现为表达减低或表达缺失。肿瘤的浸润程度、转移程度和疾病预后情况与抑癌基因的表达与否密切相关，抑癌基因失活的主要可能机制之一是基因启动子发生甲基化。二者可作为新的肿瘤标志物，指导肿瘤的早期诊断及靶基因治疗。

TSLC1和4.1B在非小细胞肺癌中的表达及临床意义

背景与目的肺癌肿瘤抑制物1(tumor suppressor in lung cancer-1,TSLC1)属于细胞粘附分子中免疫球蛋白超家族成员,肺腺癌差异表达基因(di erentially expressed in adenocarcinoma of the lung,4.1B)属于NF2/ERM/4.1蛋白超家族成员之一,两者可能通过构建相邻细胞间稳定的粘附作用而抑制恶性肿瘤的发生。本研究通过检测TSLC1和4.1B在非小细胞肺癌中的表达及其与患者临床特征的关系,分析两种基因表达的相关性,以期为临床诊断与治疗提供理论基础。方法采用RT-PCR的方法检测52例非小细胞肺癌组织以及52例相应癌旁正常肺组织中TSLC1和4.1B的表达。结果 TSLC1和4.1B在癌组织中的表达量明显低于癌旁正常肺组织(0.349±0.008vs0.555±0.010;0.209±0.040vs0.721±0.071)(P<0.01)。TSLC1和4.1B的表达与非小细胞肺癌的分化程度、TNM分期有关(P<0.05),而与患者性别、年龄、病理分型无关(P>0.05)。TSLC1与4.1B的表达呈正相关(r=0.471,P<0.001)。结论 TSLC1和4.1B在非小细胞肺癌的发生中起抑制作用,两者可能通过级联反应共同参与了非小细胞肺癌的发生和发展。TSLC1和4.1B有望成为非小细胞肺癌基因诊断与治疗的靶点。

Promoter Methylation of the <i>CADM</i>1 and 4.1<i>B</i>Genes Occurs Independently of the <i>EGFR</i>or the <i>KRAS</i>2 Mutation in Non-Small Cell Lung Cancer

Objective: Targeting mutated EGFR by EGFR-tyrosine kinase inhibitors (EGFR-TKI) is a potent approach to a subset of non-small cell lung cancer (NSCLC). However, the response to EGFR-TKI varies in individual cases even among tumors carrying the same?EGFR?mutation, suggesting the involvement of modifying factors. To characterize possible modifiers, we examined mutation state of the?EGFR?and the?KRAS?genes in Japanese NSCLC and compared them with the methylation state of lung tumor suppressors, the?CADM1 and?4.1B,?whose products have potentials to modify the functions of EGFR or KRAS. Materials and methods: A total of 103 Japanese NSCLC and 11 NSCLC cell lines were examined. Genomic DNA of exons 18–21 of the?EGFR?and exons 1 and 2 of the?KRAS?were amplified by polymerase chain reaction (PCR), followed by single-strand conformation polymorphism analysis and direct sequencing. Methylation status of gene promoters in NSCLC cells were examined by methylation-specific PCR. Results: Mutations of the?EGFR?and?KRAS?were detected mutually exclusively in 27 and 11 out of 103 NSCLC cases, respectively.?EGFR?mutations were observed exclusively in adenocarcinoma (27 of 69, 41%) and preferentially in tumors from female and non-smokers (p < 0.00001). Eight (30%) and 12 (44%) of 27 tumors carrying mutated?EGFR?and 4 (36%) and 8 (73%) of 11 tumors carrying mutated?KRAS?showed methylation of the?CADM1 and 4.1B, respectively.?EGFR-mutated tumors with methylation of either?CADM1 or 4.1B?showed more malignant features than those with unmethylated?CADM1 and 4.1B?(p < 0.05). Conclusion: Methylation state of the?CADM1 and?4.1B?are independent of the mutation status of the?EGFR?or?KRAS?but play roles in the malignant progression of NSCLC. Integration of epigenetic information would be useful for identifying possible modifiers to predict the response or recurrence of lung adenocarcinoma to the EGFR-TKI therapy.

DAL-1／4．1B在大肠癌组织中的表达及其意义

本研究旨在检测DAL-1／4．1B在大肠癌组织中的表达，探讨其在大肠癌的发牛发展中的机制。