Associations of miRNA-146a and miRNA-223 with Rheumatoid Arthritis and Their Predictive Values.

Purpose: To analyze the independent associations of miRNA-146a and miRNA-223 with rheumatoid arthritis (RA) and evaluate their predictive values for RA. Patients and Methods: A total of 68 RA patients were selected as cases, and meanwhile 68 patients with a traumatic knee condition were selected as controls by matching to the cases according to sex and age at the ratio of 1:1. The independent associations of miRNA-146a and miRNA-223 with RA were identified by binary logistic regression analysis. Receiver operating characteristic (ROC) curve was used to evaluate their predictive values for RA. Results: MiRNA-146a and miRNA-223 expression levels in both synovial tissues and serums were statistically higher in cases than in controls, and their expression levels in serums were not statistically different from those in synovial tissues in both cases and controls. The expression levels of miRNA-146a and miRNA-223 in synovial tissues were independently associated with RA, as well as the expression levels of miRNA-146a and miRNA-223 in serums. The area under curve (AUC) of combination of miRNA-146a and miRNA-223 in synovial tissues for the prediction of RA was 0.910 [95% confidence interval (CI): 0.863-0.962], and the AUC of combination of miRNA-146a and miRNA-223 in serums was 0.904 (95% CI: 0.851-0.957). Their difference was not statistically significant (P=0.873), but the AUC of combination prediction was statistically higher than those of individual predictions (synovial tissues: 0.910 vs 0.773, P=0.005, 0.910 vs 0.788, P=0.009; serums: 0.904 vs 0.766, P=0.005, 0.904 vs 0.784, P=0.011). Conclusion: MiRNA-146a and miRNA-223 in both synovial tissues and serums could be applied in predicting RA, and their combination could elevate the predictive value significantly.

Clinical application of enhanced recovery after surgery in lumbar disk herniation patients undergoing dynamic stabilization and discectomy.

BACKGROUND: Enhanced recovery after surgery (ERAS) has been demonstrated to improve early postoperative outcomes and is becoming a crucial component of any perioperative management paradigm. OBJECTIVE: To investigate the effect of an ERAS protocol on lumbar disk herniation (LDH) patients undergoing dynamic stabilization and discectomy. METHODS: A total of 119 lumbar disk herniation (LDH) patients undergoing Dynesys dynamic stabilization and discectomy were divided into the ERAS (n1 = 56) and control group (n2 = 63). ERAS group received an enhanced recovery after surgery (ERAS) protocol, and control group received a traditional care protocol. RESULTS: Both the ERAS and control groups had significantly decreased visual analog scale (VAS) score and Oswestry Disability Index (ODI) and increased Japanese Orthopaedic Association (JOA) score at postoperative 1 week, 1 month and 3 months compared with preoperative scores. Moreover, the ERAS group had lower postoperative VAS score and ODI and higher postoperative JOA score and rate of improved JOA score compared with the control group. Intraoperative blood loss, operation time, ambulation time and length of stay were all lower in the ERAS group than in the control group. CONCLUSIONS: The ERAS protocol designed was feasible for LDH patients undergoing dynamic stabilization and discectomy with significantly improved perioperative outcomes.

Prognostic implications of Kindlin proteins in human osteosarcoma.

The Kindlin protein family, comprising Kindlin-1, Kindlin-2 and Kindlin-3, play important roles in various human cancers. Here, to explore the clinical significance of Kindlins in human osteosarcomas, quantitative real-time PCR and Western blot analyses were performed to detect the expression of Kindlin-1, Kindlin-2 and Kindlin-3 mRNAs and proteins in 20 self-pairs of osteosarcoma and adjacent noncancerous tissues. Then, immunohistochemistry was performed to examine subcellular localizations and expression patterns of Kindlin proteins in 100 osteosarcoma and matched adjacent noncancerous tissues. Kindlin-1, Kindlin-2 and Kindlin-3 protein immunostainings were localized in the cytoplasm, nucleus and cytoplasm, respectively, of tumor cells in primary osteosarcoma tissues. Statistically, the expression levels of Kindlin-1 and Kindlin-2 mRNAs and proteins in osteosarcoma tissues were all significantly higher (both P<0.01), but those of Kindlin-3 mRNA and protein were both dramatically lower (both P<0.05), than in matched adjacent noncancerous tissues. In addition, the overexpressions of Kindlin-1 and Kindlin-2 proteins were both significantly associated with high tumor grade (both P=0.01), presence of metastasis (both P=0.006), recurrence (both P=0.006) and poor response to chemotherapy (both P=0.02). Moreover, Kindlin-1 and Kindlin-2 expressions were both identified as independent prognostic factors for overall (both P=0.01) and disease-free (P=0.02 and 0.01, respectively) survivals of osteosarcoma patients. However, no associations were observed between Kindlin-3 expression and various clinicopathologic features and patients' prognosis. In conclusion, aberrant expression of Kindlin-1 and Kindlin-2 may function as reliable markers for progression and prognosis in osteosarcoma patients, especially for tumor recurrence.

Upregulation of micro-ribonucleic acid-128 cooperating with downregulation of PTEN confers metastatic potential and unfavorable prognosis in patients with primary osteosarcoma.

OBJECTIVE: Abnormal expression of micro-ribonucleic acid (miRNA [miR])-128 has been observed in various human cancer types, and its validated target genes are implicated in cancer-related cellular processes, such as cell proliferation, differentiation, and apoptosis. Especially, it has been demonstrated that miR-128 may play an important role in the proliferation of human osteosarcoma cells in vitro by directly inhibiting PTEN, which functions as a tumor suppressor in this malignancy. In the current study, we investigated the involvement of miR-128 and its target gene PTEN in tumor progression and prognosis in patients with primary osteosarcoma. MATERIALS AND METHODS: Expression levels of miR-128 and PTEN messenger RNA in osteosarcoma and noncancerous bone tissues obtained from 100 patients with primary osteosarcoma were detected by quantitative real-time polymerase chain reaction. RESULTS: Expression levels of miR-128 and PTEN messenger RNA in osteosarcoma tissues were significantly higher and lower, respectively, than those in noncancerous bone tissues (both P<0.001). In addition, high miR-128 expression and low PTEN expression, alone (miR-128-high or PTEN-low) or combined (miR-128-high/PTEN-low), were all dramatically associated with poor response to chemotherapy and positive metastasis. More importantly, the associations of miR-128-high/PTEN-low expression with these clinicopathological parameters were more significant than miR-128-high or PTEN-low alone. Finally, miR-128 expression, PTEN expression, miR-128/PTEN expression, the response to chemotherapy and the metastatic status were all identified as independent prognostic factors for overall survival and disease-free survival. CONCLUSION: These findings indicate for the first time that the deregulation of miR-128 and its target gene PTEN may be involved in the aggressive progression of human osteosarcoma. Notably, the upregulation of miR-128 cooperating with the downregulation of PTEN may confer an unfavorable prognosis in patients with this malignancy.

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.

Clinical significance of microRNA-183/Ezrin axis in judging the prognosis of patients with osteosarcoma.

MicroRNA-183 (miR-183) has been demonstrated to be a tumor suppressor miRNA in inhibition of migration and invasion of osteosarcoma by targeting an oncogene Ezrin. The aim of the present study was to determine the correlation of combined miR-183 and Ezrin mRNA expression with clinicopathologic features and prognosis in patients with osteosarcomas. Expressions of MiR-183 and Ezrin mRNA were both examined using quantitative real-time reverse transcriptase-polymerase chain reaction analysis in 68 specimens from patients with osteosarcomas. MiR-183 and Ezrin mRNA expression levels were, respectively, lower and higher in osteosarcoma tissues than those in noncancerous bone tissues significantly (both P < 0.001). Notably, the downregulation of miR-183 was negatively correlated with the upregulation of Ezrin mRNA in osteosarcoma tissues (r = -0.66, P = 0.01). In addition, the combined miR-183 downregulation and Ezrin upregulation (miR-183-low/Ezrin-high) was significantly associated with high tumor grade (P = 0.02), poor response to chemotherapy (P = 0.01), positive metastasis (P = 0.006) and recurrence (P = 0.008). Moreover, miR-183/Ezrin expression and the status of metastasis were both found to be independent prognostic factors for overall survival (P = 0.02 and 0.01, respectively) and disease-free survival (both P = 0.02). Our findings showed that the aberrant expression of miR-183 and its target gene Ezrin may play a crucial role in the development and progression of human osteosarcoma. More interestingly, the dysregulation of miR-183/Ezrin axis may be related to the prediction of aggressiveness and poor prognosis for patients with this lethal disease.