Osteosarcoma (OS) is a malignant neoplasia in bone, characterized with main occurrence in teenagers. Calycosin (CC), a bioactive compound, is found to play potent pharmacological effects against cancer. Our previous study indicates CC-exerted benefits for anti-OS effect. However, further molecular mechanism behind this action needs to be investigated. In this study, human OS samples and clinical data were collected and used for further test and analysis. In addition, human osteosarcoma cell line (143B) and tumor-xenograft nude mice were used to evaluate antineoplastic activities of CC through a series of biochemical methods and immunoassays, respectively. Compared with non-OS controls, human OS samples showed increased levels of neoplastic microRNA-223 (miR-223), and elevated expressions of NF-κBp65, IκBα proteins in tumor cells. In cell culture study, CC-treated 143B cells showed reduced cell growth, increased lactic dehydrogenase (LD) content, and downregulated cellular miR-223 level. Immunolabeled cells of proliferating cell nuclear antigen, B-cell lymphoma 2 (Bcl-2), poly(ADP-ribose) polymerase (PARP) in CC treatments were decreased dose-dependently, while caspase-3 positive cells were elevated.Further, protein expressions of NF-κBp65, IκBα in CC-treated cells were downregulated. In addition, tumor-xenograft nude mice followed by CC treatments exhibited reductions of tumor mass, miR-223 levels, and Bcl-2, PARP-positive cells, as well as downregulations of NF-κBp65, IκBα protein expressions in OS samples. Taken together, these experimental findings reveal that CC exhibits potential pharmacological activities against OS through inducing apoptosis and inhibiting miR-223-IκBα signaling pathway in neoplastic cells. K E Y W O R D S apoptosis, calycosin, IκBα, miR-223, osteosarcoma

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Background The purpose of this study was to investigate the significance of preoperative C-reactive protein-to-albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting overall survival (OS) of osteosarcoma, to establish a nomogram of an individualized prognostic prediction model for osteosarcoma. Methods Two hundred thirty-five patients with osteosarcoma from multiple centers were included in this study. Receiver operating characteristic (ROC) and Youden index were used to determine the optimal cutoff values ​​for CAR, NLR, and PLR. Univariate analysis using COX proportional hazards model to identify factors associated with OS in osteosarcoma, and multivariate analysis of these factors to identify independent prognostic factors. R software (4.1.3-win) rms package was used to build a nomogram, and the concordance index (C-index) and calibration curve were used to assess model accuracy and discriminability. Results Univariate analysis revealed that the OS of osteosarcoma is significantly correlated (P < 0.05) with CAR, NLR, PLR, Enneking stage, tumor size, age, neoadjuvant chemotherapy (NACT), and high alkaline phosphatase. Multivariate analysis confirmed that CAR, NLR, Enneking stage, NACT and tumor size are independent prognostic factors for OS of osteosarcoma. The calibration curve shows that the nomogram constructed from these factors has acceptable consistency and calibration capability. Conclusion Preoperative CAR and NLR were independent predictors of osteosarcoma prognosis, and the combination of nomogram model can realize individualized prognosis prediction and guide medical practice.

This study aimed to investigate the value of the product of peripheral blood platelet and serum C-reactive protein (P-CRP), an inflammatory indicator, for the prognosis of patients with osteosarcoma. Patients with osteosarcoma who were diagnosed and treated at the First Affiliated Hospital of Guangxi Medical University, China, between January 2012 and December 2019 were included in this retrospective study. Receiver operating characteristic curves were used to calculate the optimal cut-off values for inflammatory indicators such as P-CRP, the C-reactive protein/albumin ratio (CRP/Alb), the neutrophil-lymphocyte ratio (NLR), and the platelet-lymphocyte ratio (PLR) in the peripheral blood of patients before treatment. Based on the cut-off values, the patients were divided into high P-CRP and low P-CRP groups, high CRP/Alb and low CRP/Alb groups, high NLR and low NLR groups, and high NLR and low NLR groups; the Kaplan-Meier method was used to compare the overall survival (OS) rates and OS times of the above groups. Univariate and multivariate Cox regression models were used to analyze the effects of various factors on the prognosis of osteosarcoma and to determine the independent influencing factors. The Kaplan-Meier survival analysis results suggested that the OS rate of the high P-CRP group was significantly lower than that of the low P-CRP group (14.0% vs 67.2%, P < .001). The univariate analysis results suggested that tumor volume, tumor stage, NLR, PLR, P-CRP and CRP/Alb were factors that affected the prognosis of patients with osteosarcoma, and the differences were statistically significant (P < .05). The multivariate analysis results showed that tumor volume (hazard ratio [HR] = 1.061; 95% CI, 1.001-1.125; P = .046) and preoperative P-CRP (HR, 1.037; 95% CI, 1.024-1.050; P < .01) were independent prognostic factors affecting the OS rate after osteosarcoma surgery. The results of our study showed that P-CRP is a novel and promising prognostic indicator for patients with osteosarcoma. The higher the P-CRP level in the peripheral blood of patients is before treatment, the worse the prognosis might be.Abbreviations: CRP = C-reactive protein, CRP/Alb = C-reactive protein/albumin ratio, HR = hazard ratio, NLR = neutrophillymphocyte ratio, OS = overall survival, P-CRP = the product of peripheral blood platelet and serum C-reactive protein, PLR = platelet-lymphocyte ratio.