title: A novel in silico reverse-transcriptomics-based identification and blood-based validation of a panel of sub-type specific biomarkers in lung cancer.
abstract: 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.
authors.forename: Debmalya
authors.initials: D
authors.lastname: Barh
authors.forename: Neha
authors.initials: N
authors.lastname: Jain
authors.forename: Sandeep
authors.initials: S
authors.lastname: Tiwari
authors.forename: John K
authors.initials: JK
authors.lastname: Field
authors.forename: Elena
authors.initials: E
authors.lastname: Padin-Iruegas
authors.forename: Alvaro
authors.initials: A
authors.lastname: Ruibal
authors.forename: Rafael
authors.initials: R
authors.lastname: López
authors.forename: Michel
authors.initials: M
authors.lastname: Herranz
authors.forename: Antaripa
authors.initials: A
authors.lastname: Bhattacharya
authors.forename: Lucky
authors.initials: L
authors.lastname: Juneja
authors.forename: Cedric
authors.initials: C
authors.lastname: Viero
authors.forename: Artur
authors.initials: A
authors.lastname: Silva
authors.forename: Anderson
authors.initials: A
authors.lastname: Miyoshi
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
authors.forename: Kenneth
authors.initials: K
authors.lastname: Blum
authors.forename: Vasco
authors.initials: V
authors.lastname: Azevedo
authors.forename: Preetam
authors.initials: P
authors.lastname: Ghosh
authors.forename: Triantafillos
authors.initials: T
authors.lastname: Liloglou
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D003198:Computer Simulation; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D058977:Molecular Sequence Annotation; D016133:Polymerase Chain Reaction; D015203:Reproducibility of Results; D048348:Reverse Transcription / Q000235:genetics*; D055752:Small Cell Lung Carcinoma / Q000097:blood / Q000235:genetics / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D014157:Transcription Factors