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Validation of gene expression biomarkers for cervical intraepithelial neoplasia
Author(s) -
Steinau Martin,
Rajeevan Mangalathu S,
Lee Daisy R,
Ver Suzanne D,
Ruffin Mack T,
Horowitz Ira R,
Flowers Lisa C,
Tagros Talaat S,
Birdsong George,
Husain Mujtaba,
Unger Elizabeth R
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1326-b
Efforts to discover biomarkers for reliable early detection of cervical cancer have resulted in numerous candidate molecules that are dysregulated in neoplastic cells. However, their performance in clinical samples such as Pap smear specimens remains to be demonstrated. We used real time RT‐PCR with a SYBR green assay to validate 40 candidate genes; 13 markers identified from our microarray data, 27 from current literature. Cytological samples were collected from 47 women with CIN 3 or worse and 94 age, race and HPV matched (2:1) without disease. Reproducible Ct values in at least 75% of the samples were normalized to an empirically established reference. We applied ROC curve analysis to identify 12 genes with an AUC > 0.6. MCM5 and ClDN1 had the greatest diagnostic value and an OR > 2 determined by logistic regression analysis. While some cell cycle markers MCM 5, 6, 7, CDC6, PCNA and Ki67 correlated considerably, others like Claudin1 and Notch1 were independent. Combining 11 markers with individual cutoffs set at 90% specificity, 40 of 47 CIN3s were identified (81% sensitivity, 40% specificity). Interestingly, controls that were also implicated by several genes developed cervical abnormalities within 2 years. The results indicate that gene expression in cervical cytology samples can be used to detect CIN3. A well chosen panel of biomarker could aid and markedly improve routine screening. Supported by NCI?s EDRN Interagency Agreement Y1‐CN‐0101‐01.