Document Detail

Exploiting FOXM1-orchestrated molecular network for early squamous cell carcinoma diagnosis and prognosis.
MedLine Citation:
PMID:  23034676     Owner:  NLM     Status:  MEDLINE    
Histopathological discordance with molecular phenotype of many human cancers poses clinically challenging tasks for accurate cancer diagnosis, which impacts on treatment strategy and patient outcome. Hence, an objective, accurate and quantitative method is needed. A quantitative Malignancy Index Diagnostic System (qMIDS) was developed based on 14 FOXM1 (isoform B)-associated genes implicated in the regulation of the cell cycle, differentiation, ageing, genomic stability, epigenetic and stem cell renewal, and two reference genes. Their mRNA expression levels were translated via a prospectively designed algorithm, into a metric scoring system. Subjects from UK and Norway (n = 299) provided 359 head and neck tissue specimens. Diagnostic test performance was assessed using detection rate (DR) and false-positive rate (FPR). The median qMIDS scores were 1.3, 2.9 and 6.7 in healthy tissue, dysplasia and head and neck squamous cell carcinomas (HNSCC), respectively (UK prospective dataset, p<0.001); 1.4, 2.3 and 7.6 in unaffected, oral lichen planus, or HNSCC, respectively (Norwegian retrospective dataset with up to 19 years survival data, p<0.001). At a qMIDS cut-off of 4.0, DR was 94% and FPR was 3.2% (Norwegian dataset); and DR was 91% and FPR was 1.3% (UK dataset). We further demonstrated the transferability of qMIDS for diagnosing premalignant human vulva (n = 58) and skin (n = 21) SCCs, illustrating its potential clinical use for other cancer types. This study provided evidence that qMIDS was able to quantitatively diagnose and objectively stratify cancer aggressiveness. With further validation, qMIDS could enable early HNSCC detection and guide appropriate treatment. Early treatment intervention can lead to long-term reduction in healthcare costs and improve patient outcome.
Muy-Teck Teh; Iain L Hutchison; Daniela Elena Costea; Evelyn Neppelberg; Per Gunnar Liavaag; Karin Purdie; Catherine Harwood; Hong Wan; Edward W Odell; Allan Hackshaw; Ahmad Waseem
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-10-25
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  132     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-02-19     Completed Date:  2013-05-07     Revised Date:  2014-07-22    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2095-106     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 UICC.
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MeSH Terms
Carcinoma, Squamous Cell / diagnosis*,  genetics
Cells, Cultured
Early Diagnosis
Forkhead Transcription Factors / genetics*
Gene Expression Profiling
Gene Regulatory Networks
Head and Neck Neoplasms / diagnosis*,  genetics
Keratinocytes / cytology,  metabolism
Lymphatic Metastasis
Middle Aged
Precancerous Conditions / diagnosis*,  genetics
Prospective Studies
RNA, Messenger / genetics
Reverse Transcriptase Polymerase Chain Reaction
Skin Neoplasms / diagnosis*,  genetics
Tumor Markers, Biological / genetics*
Vulvar Neoplasms / diagnosis*,  genetics
Grant Support
13044//Cancer Research UK; //Cancer Research UK
Reg. No./Substance:
0/FOXM1 protein, human; 0/Forkhead Transcription Factors; 0/RNA, Messenger; 0/Tumor Markers, Biological

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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