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2017 ; 13
(5
): 3057-3065
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MicroRNA-335 and its target Rock1 synergistically influence tumor progression and
prognosis in osteosarcoma
#MMPMID28521412
Wang Y
; Wang N
; Zeng X
; Sun J
; Wang G
; Xu H
; Zhao W
Oncol Lett
2017[May]; 13
(5
): 3057-3065
PMID28521412
show ga
MicroRNA (miR)-335 and Rho-associated serine-threonine protein kinase 1 (Rock1)
is ectopically expressed in multiple malignant tumors including osteosarcoma. The
present study aimed to clarify whether the combined ectopically expressed miR-335
and Rock1 was correlated with clinicopathological features and prognosis in
patients with osteosarcoma. The expression of miR-335 and Rock1 in 91
osteosarcoma tissue samples and 47 noncancerous bone tissues were determined
respectively by in situ hybridization and immunohistochemistry. The association
between miR-335 and Rock1 expression with the clinicopathological features of
osteosarcoma was calculated using the Pearson's ?(2) test. Spearman's correlation
analysis was used to study the association between the miR-335 and Rock1
expression. Survival curves were drawn using the Kaplan-Meier method. Univariate
and multivariate analysis was performed using the Cox's proportional hazard
regression model to allow the prognostic values to be assessed. Expression levels
of miR-335 were significantly reduced in osteosarcoma tissues (P<0.001), compared
with that in noncancerous bone tissues, while Rock1 expression was significantly
increased in osteosarcoma tissues (P<0.001). A strong correlation between miR-335
and Rock1 expression was also shown (P<0.001). Decreased miR-335 expression was
identified to be positively associated with higher clinical stage (P=0.004) and
distant metastasis (P=0.016), while elevated expression levels of Rock1 was
positively associated with a larger tumor size (P=0.013), higher clinical stage
(P=0.027) and distant metastasis (P=0.022). The combined high expression of Rock1
and low expression of miR-335 was clearly associated with distant metastasis
(P=0.010) and a higher clinical stage (P=0.010). Patients with elevated Rock1 or
decreased miR-335 expression exhibited a worse overall survival (OS) and
disease-free survival (DFS) compared with patients with decreased Rock1 or
increased miR-335 (P<0.001 for the two). In addition, patients with decreased
miR-335 and increased Rock1 had the worst OS and DFS (P<0.001 for the two). In
multivariate survival analysis, clinical stage (P=0.002 for DFS, P=0.015 for OS),
distant metastasis (P=0.024 for DFS, P=0.002 for OS), low expression of miR-335
(P<0.001 for DFS, P=0.002 for OS) and combined depressed miR-335 and elevated
Rock1 (P=0.021 for DFS, P=0.050 for OS) expression remained as the independent
prognostic factors for DFS and OS. The present findings suggest that there may be
an association between the combined downregulation of miR-335 and upregulation of
Rock1 with tumor progression and adverse prognosis in patients with osteosarcoma.