A novel in silico reverse-transcriptomics-based identification and blood-based validation of a panel of sub-type specific biomarkers in lung cancer
| Autor: | Kenneth Blum, John K. Field, Debmalya Barh, Michel Herranz, Lucky Juneja, Anderson Miyoshi, Neha Jain, Elena Padin-Iruegas, Preetam Ghosh, Anil Kumar, Álvaro Ruibal, Vasco Azevedo, Sandeep Tiwari, Triantafillos Liloglou, Rafael López, Antaripa Bhattacharya, Artur Silva, Cedric Viero |
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| Předmět: |
Lung Neoplasms
In silico Biology Bioinformatics medicine.disease_cause Polymerase Chain Reaction 03 medical and health sciences 0302 clinical medicine Carcinoma Non-Small-Cell Lung Biomarkers Tumor Genetics medicine Humans Computer Simulation Gene Regulatory Networks Lung cancer 030304 developmental biology 0303 health sciences Research Gene Expression Profiling Cell Cycle Reproducibility of Results Cancer Molecular Sequence Annotation Reverse Transcription medicine.disease Molecular diagnostics Small Cell Lung Carcinoma respiratory tract diseases 3. Good health Gene Expression Regulation Neoplastic Gene expression profiling MicroRNAs 030220 oncology & carcinogenesis Cancer research Adenocarcinoma Carcinogenesis Transcription Factors Biotechnology |
| Zdroj: | Scopus-Elsevier BMC Genomics |
| Popis: | Lung cancer accounts for the highest number of cancer-related deaths worldwide. Early diagnosis significantly increases the disease-free survival rate and a large amount of effort has been expended in screening trials and the development of early molecular diagnostics. However, a gold standard diagnostic strategy is not yet available. Here, based on miRNA expression profile in lung cancer and using a novel in silico reverse-transcriptomics approach, followed by analysis of the interactome; we have identified potential transcription factor (TF) markers that would facilitate diagnosis of subtype specific lung cancer. A subset of seven TF markers has been used in a microarray screen and was then validated by blood-based qPCR using stage-II and IV non-small cell lung carcinomas (NSCLC). Our results suggest that overexpression of HMGA1, E2F6, IRF1, and TFDP1 and downregulation or no expression of SUV39H1, RBL1, and HNRPD in blood is suitable for diagnosis of lung adenocarcinoma and squamous cell carcinoma sub-types of NSCLC. Here, E2F6 was, for the first time, found to be upregulated in NSCLC blood samples. The miRNA-TF-miRNA interaction based molecular mechanisms of these seven markers in NSCLC revealed that HMGA1 and TFDP1 play vital roles in lung cancer tumorigenesis. The strategy developed in this work is applicable to any other cancer or disease and can assist in the identification of potential biomarkers. |
| Databáze: | OpenAIRE |
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