Prognostic value of microRNA-223/epithelial cell transforming sequence 2 signaling in patients with osteosarcoma.
MicroRNA-223 (miR-223) has been demonstrated to be implicated in cell proliferation and cell cycle progression of osteosarcoma cell lines by regulating its target gene epithelial cell transforming sequence 2 (ECT2). However, the clinical significance of the deregulation of the miR-223/Ect2 axis in human osteosarcoma has not been fully elucidated. To address this problem, we firstly showed that the expression levels of miR-223 and Ect2 messenger RNA were, respectively, down-regulated and up-regulated in osteosarcoma tissues compared with those in noncancerous bone tissues significantly (both P < .001), according to the results of quantitative real-time reverse transcription-polymerase chain reaction. Notably, miR-223 down-regulation was negatively correlated with Ect2 messenger RNA up-regulation in osteosarcoma tissues (r = -0.68, P = .01). Then, the combined low miR-223 expression and high Ect2 expression (miR-223-low/Ect2-high) was significantly associated with high tumor grade (P = .01), poor response to chemotherapy (P = .01), positive metastasis (P < .001), and recurrence (P < .001) of osteosarcomas. Moreover, patients with miR-223-low/Ect2-high expression had the shortest overall survival (P < .001) and disease-free survival (P < .001) compared with patients in the other 3 groups (miR-223-low/Ect2-low, miR-223-high/Ect2-high, and miR-223-high/Ect2-low). Furthermore, the multivariate analysis identified miR-223/Ect2 expression and the status of metastasis as independent prognostic factors for overall survival and disease-free survival. In conclusion, our data offer convincing evidence that the deregulation of miR-223 and its target gene ECT2 may be associated with the aggressive tumor progression of human osteosarcoma. Of note, the combined miR-223 down-regulation and Ect2 up-regulation may be a possible marker of poor prognosis in this malignancy.
Department of Orthopedics Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, 230000, China. Electronic address: shaqiangzhanghao@163.com.
Haoshaqiang
H
Zhang
Department of Orthopedics Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, 230000, China.
Zongsheng
Z
Yin
Department of Orthopedics Surgery, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830000, China.
Kai
K
Ning
Department of Orthopedics Surgery, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830000, China.
Lei
L
Wang
Department of Orthopedics Surgery, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830000, China.
Rui
R
Guo
Department of Orthopedics Surgery, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830000, China.
Zhe
Z
Ji
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001859:Bone Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002648:Child; D018572:Disease-Free Survival; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D012516:Osteosarcoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D055815:Young Adult
D014408:Biomarkers, Tumor; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; C489850:ECT2 protein, human; C525067:MIR223, human
Clinicopathological features; Disease-free survival; Epithelial cell transforming sequence 2; MicroRNA-223; Osteosarcoma; Overall survival