MiRNA-based expression signatures in differential diagnosis of enchondroma and chondrosarcoma
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Published on: October 4, 2019
Annabell Walter1,2, Kathrin Katenkamp3,2, Nikolaus Gaßler3,2
1Abteilung für Hämatologie und Internistische Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany.
Background:
The clinical and histological differentiation of benign enchondroma from malignant chondrosarcoma remains a major challenge. Due to their histological similarity, discrimination of enchondroma from low-grade chondrosarcoma G1/ACT particularly complicates accurate diagnosis. MicroRNAs (miRNAs) are promising biomarkers to identify chondrogenic tumors.
Materials And Methods:
The expression of miR-138-5p, miR-181a-5p, miR-143-3p, and miR-145-5p was assessed by RT-qPCR in tissue samples, as well as in platelets and plasma from healthy donors and patients with enchondroma or chondrosarcoma.
Results And Discussion:
In chondrogenic tumor tissue compared to adjacent non-tumor tissue the expression of miR-138-5p was significantly increased in enchondroma and low- grade chondrosarcoma G1/ACT, whereas miR-181a-5p expression revealed no significant difference. In contrast, miR-143-3p expression was significantly downregulated in enchondroma and high-grade chondrosarcoma G2 and G3, whereas miR-145-5p exhibited significant downregulation in low-grade chondrosarcoma G1/ACT and high-grade chondrosarcoma G2 relative to the corresponding adjacent non-tumorous tissue. Comparing expression of miR-138-5p, miR-181a-5p, miR-143-3p, and miR-145-5p in enchondroma to chondrosarcoma of different grades, miR-145-5p was significantly decreased in low-grade as well as in high-grade chondrosarcoma and significantly differentiated enchondroma from chondrosarcoma in tissue samples. Analysis in platelets of enchondroma and low-grade chondrosarcoma G1/ACT patients compared to healthy donors revealed no significant change in expression. However, in human plasma significant downregulation of miR-181a-5p and miR-143-3p in enchondroma and low-grade chondrosarcoma G1/ACT patients compared to healthy donors with corresponding ROC curves was demonstrated.
Conclusion:
While miR-138-5p and miR-143-3p show potential as tissue-based biomarkers for chondrogenic tumors, miR-145-5p appears to be particularly promising in differentiating enchondroma from chondrosarcoma of all grades. MiR-181a-5p and miR-143-3p exhibit diagnostic value in plasma. However, these findings are exploratory and larger, multicenter studies with independent validation cohorts are essential to confirm their clinical utility to establish robust diagnostic thresholds.
