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MiRNA-based expression signatures in differential diagnosis of enchondroma and chondrosarcoma
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.
