Combined fibrinogen and neutrophil-lymphocyte ratio as a biomarker in predicting recurrence of giant cell tumor of bone.

Aims: The present study investigated the combined clinical significance of fibrinogen and neutrophil-lymphocyte ratio (F-NLR) in predicting postoperative recurrence of giant cell tumor of bone. Methods: A total of 113 participants were included in this retrospective study to examine the effects of inflammatory factors on postoperative tumor recurrence. Results: The high-score F-NLR group was significantly associated with larger tumor size (p = 0.001), advanced tumor stage (p = 0.018), wide resection (p = 0.004) and greater local recurrence (p = 0.014). Univariate and multivariate survival analyses revealed that F-NLR (p = 0.035) remained an independent factor influencing tumor recurrence rates. Conclusions: This study reveals that the F-NLR score is a promising blood biomarker for predicting giant cell tumor recurrence.

Giant cell tumor of bone (GCT) is predominantly regarded as an intermediate, locally destructive but rarely metastasizing tumor with recurrence potential and peak incidence in the second to fourth decades of life. The treatment of GCT is often difficult due to local recurrence. Therefore, a new indicator is urgently needed to predict postoperative recurrence more accurately in patients with GCT. The preoperative combined fibrinogen and neutrophil­lymphocyte ratio as a predictor of tumor recurrence and prognosis in GCT patients has been assessed. The present study is the first to demonstrate that a grading system based on the fibrinogen and neutrophil­lymphocyte ratio score is an easily determined, meaningful and reproducible biomarker for predicting recurrence in GCT patients.

Biomechanical analysis of locking plates for fixation of metacarpal shaft fractures: A finite element analysis.

BACKGROUND: There appears to be a paucity of knowledge about the biomechanics of locking plates for the fixation of metacarpal shaft fractures. A thorough understanding of the biomechanics of locking plates is needed to apply them correctly, optimize outcomes, and avoid complications. The purpose of this study is to investigate the biomechanics of the fixation of metacarpal fractures using locking plate-screw constructs with different numbers of screws. HYPOTHESIS: The difference in the number of screws in the locking plate influenced the biomechanical outcome of the metacarpal fracture. METHODS: Finite element models of third metacarpal fractures with locking plate-screw constructs were established, and the magnitude and distribution of their stresses and displacements were investigated when a vertical load of 100N was applied. RESULTS: For the metacarpal fracture with a locking plate and screws, the stress in the metacarpal was largely shared by the plate-screw construct. For the plate-screw construct, the stress is concentrated in the area close to the fracture line, and the 6-screw Group has the lowest failure risk since it has the lowest plate stress and the second-lowest screw stress. The implant-bone construct with 8 screws has better biomechanical stability because of minimal displacement, but increased stress on both the metacarpal bone and the screws, leading to increased failure rates. DISCUSSION: The stresses in the metacarpal were mostly shared by the plate-screw constructs and the screws closest to the fracture line were the most likely to break or loosen. For the implant-bone constructs, the locking plate with 2 screws was the most vulnerable to break or loosen, whereas the locking plate with 6 screws was the least likely to break or loosen. The implant-bone construct with 8 screws had better biomechanical stability, but the stresses in both the metacarpal and the screws were increased, which increased the risk of failure. LEVEL OF EVIDENCE: IV, basic science study.

The cancer-related transcription factor Runx2 combined with osteopontin: a novel prognostic biomarker in resected osteosarcoma.

PURPOSE: Osteosarcoma is the most common primary bone cancer in children and young adults. Recent experimental evidence has indicated that Runx2/OPN axis play important roles in the metastasis of osteosarcoma cells. The present study aimed to explore their relationship and prognostic significance in surgically resected osteosarcoma. METHODS: The expression of runt-related transcription factor2(Runx2) and osteopontin (OPN) in clinical specimens from 105 osteosarcoma patients were detected by immunohistochemistry. The correlations between Runx2, OPN, and clinicopathologic data were analyzed by Chi-square (χ2) tests. The prognostic values were determined by univariate and multivariate survival analysis. The accuracy of oncologic outcome prediction was evaluated by receiver-operating characteristics curves. RESULTS: The results showed there is a significant positive correlation between Runx2 and OPN expression at protein levels (P = 0.015). Runx2 and OPN were both independent predictors for overall survival and metastasis-free survival. When Runx2 and OPN were taken into consideration together, the predictive range was extended and the sensitivity was improved, and more significant and better biomarkers for osteosarcoma metastasis and survival. CONCLUSIONS: These results suggest that a combined Runx2/OPN expression could be a valuable independent predictor of tumor metastasis and survival in osteosarcoma patients.

Pre-operative prognostic nutritional index was associated with recurrence after surgery in giant cell tumor of bone patients.

OBJECTIVES: Giant cell tumors of bone (GCT) are benign with a local recurrence rate of approximately 20-50%. Growing evidence suggests that inflammation plays an important role in tumor formation and progression. Inflammatory biomarkers, including prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), have little data in predicting postoperative recurrence of GCT. METHODS: We retrospectively investigated 105 patients with surgery for GCT between March 2010 and June 2019 at our hospital. Through the analysis of receiver operating characteristics (ROC), the optimal cutoff values of PNI, NLR and PLR were determined. Clinical features between PNI, NLR and PLR were tested with the χ2 test. Univariate and multivariate analyses were applied to identify the prognostic factors. RESULTS: The optimal cut-off points of PNI, NLR and PLR were 48.6, 2.4 and 136.9, respectively. In univariate analysis, PNI, NLR, PLR, tumor size, Campanacci stage were significantly associated with recurrence-free survival (RFS). Cox multivariate regression analysis revealed that the PNI (p = 0.003) and Campanacci stage (p = 0.001) were independent prognostic factors for GCT. CONCLUSIONS: PNI can be regarded as a novel independent prognostic factor for predicting postoperative recurrence in GCT.

ONZIN Upregulation by Mutant p53 Contributes to Osteosarcoma Metastasis Through the CXCL5-MAPK Signaling Pathway.

BACKGROUND/AIMS: Gain-of-function of mutant p53 is associated with a high rate of lung metastasis in osteosarcoma. To investigate the mechanism of mutant p53-induced osteosarcoma metastasis, expression array analysis was performed, comparing non-metastatic osteosarcomas from p53+/- mice with metastatic osteosarcomas from p53R172H/+ mice. Onzin (Plac8) was identified as one of the genes upregulated in p53R172H/+ mouse metastatic osteosarcomas. Accordingly, we investigated the role of ONZIN in human osteosarcoma metastasis. METHODS: ONZIN function and its downstream targets were examined in osteosarcoma cell lines. Assays related to tumorigenesis and metastasis, including cell migration, invasion, clonogenic survival, and soft agar colony formation, were performed in osteosarcoma cells. Additionally, mouse xenograft models were used to examine the role of ONZIN overpression in tumorigenesis in vivo. Lastly, 87 osteosarcoma patients were recruited to investigate the clinical relevance of ONZIN overexpression in metastasis and prognosis. RESULTS: ONZIN overexpression enhanced osteosarcoma cell proliferation, clonogenic survival, migration, and invasion independent of p53 status. Furthermore, ONZIN overexpression induced CXCL5 upregulation and resulted in increased ERK phosphorylation, which contributed to more aggressive osteosarcoma metastatic phenotypes. More importantly, overexpression of ONZIN in human osteosarcoma patients was closely associated with lung metastasis, poor prognoses, and survival. CONCLUSIONS: Overexpression of ONZIN promotes osteosarcoma progression and metastasis, and can serve as a clinical biomarker for osteosarcoma metastasis and prognosis.

PLA2G16 promotes osteosarcoma metastasis and drug resistance via the MAPK pathway.

The prognosis of metastatic osteosarcoma is dismal and a better understanding of the mechanisms underlying disease progression is essential to improve treatment options and patient outcomes. We previously demonstrated Pla2g16 overexpression in mouse osteosarcoma contributes to metastasis phenotypes and increased expression of PLA2G16 is associated with metastasis and poor prognosis in human tumors. To further examine the mechanisms through which PLA2G16 contributes to human osteosarcoma metastasis and explore the potential of PLA2G16 as a therapeutic target in osteosarcoma, we generated a panel of human osteosarcoma cell lines expressing different levels of PLA2G16. The functional analyses of these cell lines demonstrated high levels of PLA2G16 expression increased osteosarcoma cell migration, invasion, clonogenic survival, and anchorage-independent colony formation. Importantly, this activity was dependent on the phospholipase activity of PLA2G16. Additionally, PLA2G16 overexpression decreased the sensitivity of cells to a panel of chemotherapeutic agents. Analysis of downstream pathways revealed the pro-metastasis functions of PLA2G16 were mediated through the MAPK pathway, as knockdown of PLA2G16 decreased ERK1/2 phosphorylation and pharmacological inhibition of MEK significantly repressed PLA2G16 mediated cell migration and clonogenic survival. Furthermore, PLA2G16 overexpression promoted xenograft tumor growth in vivo, and these tumors exhibit increased ERK1/2 phosphorylation. Lastly, the expression of PLA2G16 is strongly correlated with the increased ERK1/2 phosphorylation in human osteosarcoma samples, and the combined lesions are associated with reduced overall and metastasis-free survival. Collectively, these results demonstrate increased PLA2G16 expression activates the MAPK pathway to enhance osteosarcoma metastasis and may be a novel therapeutic target for these cancers.

Coexpression of CXCR4 and MMP9 predicts lung metastasis and poor prognosis in resected osteosarcoma.

Osteosarcoma is a highly aggressive bone disease with a tendency to metastasize to the lung. The 5-year survival of patients with metastatic osteosarcoma is only 20 %. Many studies have demonstrated SDF-1/CXCR4 and MMP9 play important roles in the metastasis of malignant tumors, including osteosarcoma. The aim of this study was to investigate the association of CXCR4 and MMP9 expression with clinicopathological features and pulmonary metastasis in osteosarcoma. Using tumor tissue microarrays, we analyzed the expression of CXCR4 and MMP9 among 34 primary osteosarcomas with pulmonary metastasis and 62 primary osteosarcomas without metastasis. A median time of 57.5 months (range: 6 to 171 months) follow-up was performed to evaluate tumor metastasis and the patient survival. The prognostic values were determined by univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard model analysis. The accuracy of oncologic outcome prediction was evaluated by receiver-operating characteristics (ROC) curves (AUC). The expression of CXCR4 and MMP9 was significantly correlated in tumor tissues (P = 0.026). Both CXCR4 and MMP9 were independent predictors for overall survival and metastasis-free survival by Cox multivariate analysis, and high expression for both CXCR4 and MMP9 were even more significant and better biomarkers for osteosarcoma metastasis and survival. The combination of CXCR4 and MMP9 high expression is very likely to be a valuable independent predictor of lung metastasis and survival in osteosarcoma patients.

PLA2G16 Expression in Human Osteosarcoma Is Associated with Pulmonary Metastasis and Poor Prognosis.

BACKGROUND: Osteosarcoma is the most frequent type of malignant bone tumor in children and adolescents and is associated with a high propensity for lung metastasis. Recent experiments have indicated that PLA2G16 contributes to osteosarcoma progression and metastasis in both mouse and human osteosarcoma cell lines. The aim of this study was to compare the expression of PLA2G16 in non-metastatic and metastatic osteosarcomas to determine whether PLA2G16 expression can serve as a biomarker of osteosarcoma prognosis and metastasis. METHODS: Quantitative real-time PCR was used to examine PLA2G16 mRNA in primary osteosarcoma patients (18 patients without metastases and 17 patients with metastases), and immunohistochemistry (IHC) staining of PLA2G16 was performed on tissue microarrays from 119 osteosarcoma patients. Tumor metastatic behavior and survival of the patients were followed up for a minimum of 36 months and a maximum of 171 months. The prognostic value of PLA2G16 expression was evaluated by the Kaplan-Meier method and a log-rank test. Multivariate Cox regression analysis was used to identify significant independent prognostic factors. RESULTS: Osteosarcoma patients with metastasis showed a higher expression of PLA2G16 at both the mRNA and protein levels (both at P values< 0.05) than did patients without metastasis. Osteosarcoma patients with positive IHC staining of PLA2G16 expression at primary sites had shorter overall survival and metastasis-free survival (both at P values <0.02). Moreover, multivariate Cox analysis identified PLA2G16 expression as an independent prognostic factor to predict poor overall survival and metastasis-free survival (both P values < 0.03). CONCLUSIONS: This study indicated that PLA2G16 expression is a significant prognostic factor in primary osteosarcoma patients for predicting the development of metastases and poor survival.