Diagnostic and prognostic impact of desmocollins in human lung cancer.
نویسندگان
چکیده
OBJECTIVE Desmosomes are intercellular junctions that confer strong cell-cell adhesion. Two main members of desmosomal cadherins, desmogleins (DSGs) and desmocollins (DSCs), are involved in carcinogenesis. However, their role in human lung cancer remained elusive. The aims of this study were to analyse the expression of DSCs and to evaluate their clinical application in lung cancer. METHODS The expression of DSC1-3 mRNAs was analysed by RT-PCR. The methylation status of DSCs was analysed by demethylation tests and bisulphite sequencing. Protein expression of DSCs in primary lung cancer was evaluated by immunohistochemistry on tissue microarrays. RESULTS DSC1-3 mRNAs were downregulated in lung cancer cells, and the expression was restored in four out of seven cell lines, respectively, after 5-aza-2'-deoxycytidine treatment. A heterogeneous methylation pattern was detected by bisulphite sequencing in exon 1 of DSC2 and DSC3. In 199 patients with primary lung cancer, we found that lower protein expression of DSC1 was significantly linked to worse tumour differentiation (p=0.017), DSC3 proteins were more expressed in squamous cell carcinoma (SCC) compared with adenocarcinoma (ADC) (p<0.001), and reduced expression of DSC1 and DSC3 was significantly correlated with poor clinical outcome (p=0.045 and p=0.007, respectively). CONCLUSIONS Our data suggest that downregulation of DSC1-3 may be explained by DNA methylation, DSC1 may be a marker for tumour differentiation, DSC3 has a potential diagnostic value in subclassification of non-small cell lung carcinoma into SCC and ADC, and furthermore, DSC1 and DSC3 may be prognostic markers for lung cancer.
منابع مشابه
Prognostic value of various metabolic parameters on pre-treatment 18-F-FDG PET/CT in patients with stage I-III non-small cell lung cancer
Background: the aim of this study was to investigate the prognostic value of 18Fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) parameters in both overall survival and progression-free survival in Stage I-III non-small cell lung cancer (NSCLC). Materials and Methods: In this retrospective study, 267 patients who were diagnosed as Stage I-III non-smal...
متن کاملGene-Gene Interaction Study Between Genetic Polymorphisms of Folate Metabolism and MTR SNPs on Prognostic Features Impact for Breast Cancer
Background: Breast Cancer (BC), the second leading cause of cancer mortality after lung cancer and varied across the world due to genetic and environmental factors. In this study, we evaluated the interaction between the polymorphisms in genes encoding enzymes of folate metabolism: methylenetetrahydrofolate reductase (MTHFR), methionine synthesis reductase (MTR) with the BC prognostic factors. ...
متن کاملThe Effect of Time-dependent Prognostic Factors on Survival of Non-Small Cell Lung Cancer using Bayesian Extended Cox Model
Abstract Background: Lung cancer is one of the most common cancers around the world. The aim of this study was to use Extended Cox Model (ECM) with Bayesian approach to survey the behavior of potential time-varying prognostic factors of Non-small cell lung cancer. Materials and Methods: Survival status of all 190 patients diagnosed with Non-Small Cell lung cancer referring to hospitals in ...
متن کاملHuman Cancer Modeling: Recapitulating Tumor Heterogeneity Towards Personalized Medicine
Despite diagnostic, preventive and therapeutic advances, growing incidence of cancer and high rate of mortality among patients affected by specific cancer types indicate current clinical measures are not ideally useful in eradicating cancer. Chemoresistance and subsequent disease relapse are believed to be mainly driven by the cell-molecular heterogeneity of human tumors that necessitates perso...
متن کاملHuman Cancer Modeling: Recapitulating Tumor Heterogeneity Towards Personalized Medicine
Despite diagnostic, preventive and therapeutic advances, growing incidence of cancer and high rate of mortality among patients affected by specific cancer types indicate current clinical measures are not ideally useful in eradicating cancer. Chemoresistance and subsequent disease relapse are believed to be mainly driven by the cell-molecular heterogeneity of human tumors that necessitates perso...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Journal of clinical pathology
دوره 65 12 شماره
صفحات -
تاریخ انتشار 2012