Prognostic significance of circulating microRNA-214 and -126 in dogs with appendicular osteosarcoma receiving amputation and chemotherapy

循环微小RNA-214和-126对接受截肢和化疗的犬附肢骨肉瘤的预后意义

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作者:Kazuki Heishima, Travis Meuten, Kyoko Yoshida, Takashi Mori, Douglas H Thamm

Background

Dogs with appendicular osteosarcoma (OSA) receiving standard amputation and adjuvant chemotherapy demonstrate variable outcome with treatment; however, additional biomarkers would be helpful for predicting their outcome. In the present study, we assessed the potential of circulating microRNA-214 (miR-214) and - 126 (miR-126) to predict time to metastasis and death in dogs with OSA treated with amputation and chemotherapy.

Conclusions

Circulating miR-214, - 126, and an integrated prognostic score have strong potential to predict the outcome of canine appendicular OSA patients receiving amputation and chemotherapy.

Results

Seventy-six dogs that fully met inclusion criteria were included in the analysis. The criteria included (1) a diagnosis of appendicular OSA without metastases at diagnosis, (2) treatment by amputation and chemotherapy using carboplatin, doxorubicin, cisplatin, or a combination of these agents. Circulating miR-214 and -126 levels at the time before treatment were measured by using RT-qPCR. High circulating miR-214 and serum alkaline phosphatase (ALP) significantly predicted short disease-free survival (DFS) and overall survival (OS). Conversely, high circulating miR-126 significantly predicted prolonged DFS and OS. An integrated approach using circulating miR-214, - 126, and serum ALP showed better accuracy in the prediction of DFS and OS and identification of long-term survivors than prediction using only ALP. Other variables (age, weight, sex, monocyte counts, and primary tumor site) were associated with neither DFS nor OS. miRNA levels did not strongly correlate with histopathological indices. Conclusions: Circulating miR-214, - 126, and an integrated prognostic score have strong potential to predict the outcome of canine appendicular OSA patients receiving amputation and chemotherapy.

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