RGD Reference Report - Blood-based biomarkers for detecting mild osteoarthritis in the human knee. - Rat Genome Database

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Blood-based biomarkers for detecting mild osteoarthritis in the human knee.

Authors: Marshall, KW  Zhang, H  Yager, TD  Nossova, N  Dempsey, A  Zheng, R  Han, M  Tang, H  Chao, S  Liew, CC 
Citation: Marshall KW, etal., Osteoarthritis Cartilage. 2005 Oct;13(10):861-71.
RGD ID: 10429075
Pubmed: PMID:16139532   (View Abstract at PubMed)
DOI: DOI:10.1016/j.joca.2005.06.002   (Journal Full-text)

OBJECTIVE: This study was designed to test the utility of a blood-based approach to identify mild osteoarthritis (OA) of the knee. METHODS: Blood samples were drawn from 161 subjects, including 85 subjects with arthroscopically diagnosed mild OA of the knee and 76 controls. Following RNA isolation, an in-house custom cDNA microarray was used to screen for differentially expressed genes. A subset of selected genes was then tested using real-time RT-PCR. Logistic regression analysis was used to evaluate linear combinations of the biomarkers and receiver operating characteristic curve analysis was used to assess the discriminatory power of the combinations. RESULTS: Genes differentially expressed (3543 genes) between mild knee OA and control samples were identified through microarray analysis. Subsequent real-time RT-PCR verification identified six genes significantly down-regulated in mild OA: heat shock 90kDa protein 1, alpha; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase complex-associated protein; interleukin 13 receptor, alpha 1; laminin, gamma 1; platelet factor 4 (also known as chemokine (C-X-C motif) ligand 4) and tumor necrosis factor, alpha-induced protein 6. Logistic regression analysis identified linear combinations of nine genes--the above six genes, early growth response 1; alpha glucosidase II alpha subunit; and v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (avian)--as discriminatory between subjects with mild OA and controls, with a sensitivity of 86% and specificity of 83% in a training set of 78 samples. The optimal biomarker combinations were then evaluated using a blind test set (67 subjects) which showed 72% sensitivity and 66% specificity. CONCLUSIONS: Linear combinations of blood RNA biomarkers offer a substantial improvement over currently available diagnostic tools for mild OA. Blood-derived RNA biomarkers may be of significant clinical value for the diagnosis of early, asymptomatic OA of the knee.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Knee Osteoarthritis  IEP 10429075mRNA:decreased expression:blood (human)RGD 
Knee Osteoarthritis  ISOHSP90AA1 (Homo sapiens)10429075; 10429075mRNA:decreased expression:blood (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hsp90aa1  (heat shock protein 90 alpha family class A member 1)

Genes (Mus musculus)
Hsp90aa1  (heat shock protein 90, alpha (cytosolic), class A member 1)

Genes (Homo sapiens)
HSP90AA1  (heat shock protein 90 alpha family class A member 1)


Additional Information