Prognostic Value of Programmed Cell Death 1 Ligand-1 in Patients With Bone and Soft Tissue Sarcomas: A Systemic and Comprehensive Meta-Analysis Based on 3,680 Patients.

Background: Programmed cell death 1 ligand-1 (PD-L1) is an immune checkpoint molecule that acts to protect cancer cells from immune surveillance and is considered as a prognostic biomarker in several cancers, but the prognostic value of PD-L1 in bone and soft tissue sarcomas remains inconclusive. In the present meta-analysis, the clinicopathological and prognostic value of PD-L1 in sarcomas was evaluated. Method: We performed a systemic and comprehensive meta-analysis by searching the PubMed, Medline, Cochrane Library, EMBASE, and Web of Science databases up to October 31, 2019. Eligible articles were incorporated, and pooled hazard ratios (HRs) and odds ratios (ORs) with their 95% confidence intervals (CIs) were used to estimate the outcomes. Results: Thirty-six articles containing 39 independent studies with 3,680 bone and soft tissue sarcoma patients were included in our meta-analysis. The pooled results showed that PD-L1 overexpression could predict poor overall survival (HR 1.45, 95% CI 1.11-1.90, P < 0.01), metastasis-free survival (HR 1.58, 95% CI 1.14-2.19, P < 0.01), and event-free survival (HR 2.82, 95% CI 1.69-4.71, P < 0.01) in sarcomas. Furthermore, PD-L1 overexpression was correlated with a higher rate of tumor metastasis (OR 2.95, 95% CI 1.32-6.60, P < 0.01), a more advanced tumor grade (OR 3.63, 95% CI 2.55-5.16, P < 0.01), and more T lymphocyte infiltration (OR 5.55, 95% CI 2.86-10.76, P < 0.01). No obvious publication bias was observed, and the sensitivity analysis showed that our results were robust. Conclusion: The results of our meta-analysis indicate that high PD-L1 expression might serve as a valuable and predictive biomarker for adverse clinicopathological features and poor prognosis in patients with sarcoma.

[Comparison of effectiveness between SuperPATH approach and posterolateral approach in total hip arthroplasty].

Objective: To compare the effectiveness between SuperPATH approach and posterolateral approach in total hip arthroplasty (THA). Methods: Between January 2016 and December 2016, 84 patients with hip disease were included in the study and randomly divided into 2 groups. Forty patients were treated with THA via SuperPATH approach (SuperPATH group), and 44 patients were treated with THA via posterolateral approach (PSA group). There was no significant difference in gender, age, body mass index, the type of disease, the complicating diseases, and preoperative thrombosis of lower extremity and Harris score between 2 groups ( P>0.05). The operation time, intraoperative blood loss, length of incision, postoperative drainage volume, unloaded activity time, Harris score, and short-form 36 health survey scale (SF-36) score were compared. The postoperative X-ray films were used to observe the position of joint prosthesis. Results: All patients were followed up 6-18 months (mean, 10.3 months). The operation time, intraoperative blood loss, length of incision, postoperative drainage volume, and unloaded activity time in SuperPATH group were significantly superior to those in PSA group ( P<0.05). The Harris score at 2 weeks and 1 month after operation were significantly higher in SuperPATH group than that in PSA group ( P<0.05). But there was no significant difference in the Harris scores at 3 and 6 months after operation between 2 groups ( P>0.05). At last follow-up, the SF-36 scores were higher in SuperPATH group than those in PSA group ( P<0.05). Postoperative X-ray films showed the joint prosthesis was in good position. Conclusion: THA via SuperPATH approach has the advantages of minimal invasion, safe, and rapid recovery, which is better than THA via posterolateral approach.

Silencing FAT10 inhibits metastasis of osteosarcoma.

Metastasis is the main challenge of osteosarcoma treatment. Herein, we first reveal the oncogenic role of FAT10 in metastasis of osteosarcoma. FAT10 was upregulated in osteosarcoma, especially in metastatic osteosarcoma. High level of FAT10 was associated with poorer prognosis of osteosarcoma patients. Moreover, Transwell and Matrigel assays revealed that silencing FAT10 significantly inhibited the invasive and migratory abilities of osteosarcoma cells. Metastasis assay in vivo showed that silencing FAT10 decreased the number of mice with distant metastasis. We also found that FAT10 may act its oncogenic functions through regulating HOXB9. Collectively, the results suggested that FAT10 may be a novel therapeutic target for osteosarcoma patients.

MicroRNA-603 functions as an oncogene by suppressing BRCC2 protein translation in osteosarcoma.

The present study was conducted to investigate the expression of miR-603 in osteosarcoma cells, and the effect of miR-603 on the biological behavior and expression of breast cancer cell 2 (BRCC2) in osteosarcoma cells. In the present study, qRT-PCR was used to measure the levels of miRNA and mRNA. The results showed that miR-603 was significantly upregulated in human osteosarcoma tissues and cell lines. MTT and colony formation assays were employed to evaluate the role of miR-603 in the regulation of osteosarcoma cell proliferation. The results showed that overexpression of miR-603 promoted the proliferation of MG-63 and U2OS cells. Furthermore, a nude mouse subcutaneous tumor model indicated that miR-603 promoted osteosarcoma growth in vivo. Moreover, miR-603 expression levels were increased in patients with distant metastasis in comparison with levels in patients without distant metastasis. We discovered that BRCC2 may be a target of miR-603. Our results demonstrated that overexpression of miR-603 suppressed BRCC2 protein expression, and an miR-603 inhibitor enhanced BRCC2 protein expression as determined by western blot assay and immunohistochemical analysis. Luciferase reporter assays confirmed that BRCC2 is a direct target of miR-603 in osteosarcoma cells, and the results suggest that miR-603 downregulates BRCC2 expression in osteosarcoma via translational inhibition. Finally, we found that the reduction in BRCC2 expression induced by miR-603 was responsible for the enhanced colony formation and proliferative ability noted in the MG-63 and U2OS cells. In conclusion, miR-603 enhanced osteosarcoma growth by downregulation of BRCC2 expression via translational inhibition.

Macrophage-derived microvesicles promote proliferation and migration of Schwann cell on peripheral nerve repair.

BACKGROUND: Macrophages have been implicated in peripheral nerve regeneration. However, whether macrophages-derived microvesicles (MVs) are involved in this process remains unknown. In the present study, the effects of macrophages-derived MVs on proliferation and migration of Schwann cells (SCs) were evaluated in both in vitro and in vivo. METHODS: Human monocytic leukaemia cell line (THP-1) was successfully driven to M1 and M2 phenotypes by delivery of either IFN-γ or IL-4, respectively. SCs incubated with M1 or M2 macrophages-derived MVs, the cell migration and proliferation were assessed, and expression levels of nerve growth factor (NGF) and Laminin were measured. A rat model of sciatic nerve was established and the effects of macrophages-derived MVs on nerve regeneration were investigated. RESULTS: M2-derived MVs elevated migration, proliferation, NFG and Laminin protein levels of SCs compared with M1-or M0-derived MVs. The relative expression levels of miR-223 were also increased in M2 macrophages and M2-derived MVs. Transfected M2 macrophages with miR-223 inhibitor then co-incubated with SCs, an inhibition of cell migration and proliferation and a down-regulated levels of NFG and Laminin protein expression were observed. In vivo, M2-derived MVs significantly increased the infiltration and axon number of SCs. CONCLUSION: M2-derived MVs promoted proliferation and migration of SCs in vitro and in vivo, which provided a therapeutic strategy for nerve regeneration.

MicroRNA-1908 is upregulated in human osteosarcoma and regulates cell proliferation and migration by repressing PTEN expression.

Osteosarcoma is a high-grade malignant bone neoplasm. Although the introduction of chemotherapy has reduced its mortality, >50% of patients develop chemoresistance and have an extremely poor prognosis due to pulmonary metastasis. Several molecular pathways contributing to osteosarcoma development and progression have recently been identified. Various studies have addressed the genes involved in the metastasis of osteosarcoma. However, the highly complex molecular mechanisms of metastasis remain to be elucidated. Recent studies have emphasized causative links between aberrant microRNA expression patterns and osteosarcoma progression. miR-1908 is dysregulated in certain human types of cancer. The expression pattern, clinical significance and biological role of miR-1908 in osteosarcoma, however, remain largely undefined. In the present study, we showed that miR-1908 was markedly upregulated in osteosarcoma cells and tissues compared with normal bone tissues using RT-qPCR. miR-1908 upregulation in osteosarcoma tissues was significantly associated with cell proliferation, invasion, advanced TNM stage and tumor growth. Both gain- and loss-of-function studies showed that miR-1908 markedly increased the ability of osteosarcoma cells to proliferate and to invade through Matrigel in vitro. Analyses using mouse xenograft model revealed that xenografts of miR-1908 stable-expressing osteosarcoma cells exhibited a significant increase in tumor volume and weight, compared with the control group. Subsequent investigations revealed that miR-1908 directly inhibited the expression of phosphatase and tensin homolog deleted on chromosome ten (PTEN). Using a luciferase reporter carrying the 3'-untranslated region (3'-UTR) of PTEN, we identified PTEN as a direct target of miR-1908. Collectively, the results showed that, miR-1908 promotes proliferation and invasion of osteosarcoma cells by repressing PTEN expression.