Exploiting FOXM1-Orchestrated molecular network for early squamous cell carcinoma diagnosis and prognosis.

Teh MT, Hutchison IL, Costea DE, Neppelberg E, Liavaag PG, Purdie K, Harwood C, Wan H, Odell EW, Hackshaw A, Waseem A.

Source

Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Barts & The London School of Medicine and Dentistry, Queen Mary University of London, England, United Kingdom. m.t.teh@qmul.ac.uk.

Abstract

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=".001" 1.3="1.3" 1.4="1.4" 19="19" 2.3="2.3" 3.2="3.2" 4.0="4.0" 7.6="7.6" 91="91" 94="94" a="a" able="able" aggressiveness.="aggressiveness." and="and" appropriate="appropriate" at="at" can="can" cancer="cancer" clinical="clinical" costs="costs" could="could" cut-off="cut-off" data="data" dataset="dataset" demonstrated="demonstrated" detection="detection" diagnose="diagnose" diagnosing="diagnosing" dr="dr" early="early" enable="enable" evidence="evidence" for="for" fpr="fpr" further="further" guide="guide" healthcare="healthcare" hnscc="hnscc" human="human" illustrating="illustrating" improve="improve" in="in" intervention="intervention" its="its" lead="lead" lichen="lichen" long-term="long-term" malignant="malignant" n="21)" objectively="objectively" of="of" or="or" oral="oral" orwegian="orwegian" other="other" outcome.="outcome." p="p" patient="patient" planus="planus" potential="potential" pre="pre" provided="provided" qmids="qmids" quantitatively="quantitatively" reduction="reduction" respectively="respectively" retrospective="retrospective" sccs="sccs" skin="skin" stratify="stratify" study="study" survival="survival" that="that" the="the" to="to" transferability="transferability" treatment.="treatment." treatment="treatment" types.this="types.this" unaffected="unaffected" up="up" use="use" validation="validation" vulva="vulva" was="was" we="we" with="with" years="years">Copyright © 2012 UICC.