BARX1 promotes osteosarcoma cell proliferation and invasion by regulating HSPA6 expression.

Osteosarcoma (OS) is a bone tumour affecting adolescents. Dysregulation of Barx homeobox 1 (BARX1) expression is involved in various cancers, but its function and mechanism in the process of OS are undefined. This study revealed that BARX1 expression is higher in OS tissue than in adjacent normal tissue. Downregulation of BARX1 in OS cells significantly suppressed their proliferation and migration, whereas enforced expression of exogenous BARX1 exerted the opposite effects on OS cells. Subsequently, heat shock 70-kDa protein 6 (HSPA6) expression was clearly increased after BARX1 overexpression in OS cells, as confirmed by RNA sequencing. The dual-luciferase reporter assay confirmed that HSPA6 expression is directly regulated by BARX1. The in vitro assay indicated that silencing HSPA6 expression attenuated OS proliferation and migration induced by BARX1. A dual immunofluorescence labelling assay provided further evidence that BARX1 was overexpressed and associated with HSPA6 overexpression in OS tumour tissue. In conclusion, BARX1 promotes OS cell proliferation and migration by inducing the expression of HSPA6, which plays an oncogenic role in OS. BARX1 and HSPA6 can potentially act as novel therapeutic targets for OS.

Prognostic factors and treatment outcomes of spinal osteosarcoma: Surveillance, epidemiology, and end results database analysis.

Objective: Spinal osteosarcoma is a rare osseous neoplasm. The aim of this study is to make a comprehensive analysis of the demographic features, clinicopathologic characteristics and factors affecting prognosis of spinal osteosarcoma using the Surveillance, Epidemiology and End Results (SEER) database. Methods: SEER data were reviewed to identify patients diagnosed with spinal osteosarcoma between 1975 and 2016 and determine their overall survival (OS) and disease-specifc survival (DSS). Univariate and multivariate analyses were performed using the Cox-regression proportional hazards model and Kaplan-Meier method. Results: A total of 668 patients (53.1% males) with spinal osteosarcoma were identified. The mean age at diagnosis was 45.2 years, including 67.5% patients younger than 60 years. The median OS of these patients was 15 months, and the 5-year OS was 16.8%. Multivariate analysis showed that age ≥60 year (HR=2.271, p = 0.008), high grade (HR=1.323, p = 0.008), regional stage (HR=1.658, p = 0.017), metastasis stage (HR=3.045, p < 0.001) and no-surgery treatment (HR=1.761, p < 0.001) were adversely associated with OS; gender (HR=0.657, p = 0.044), tumor grade (HR=1.616, p = 0.006), tumor stage (HR=3.329, p = 0.011; HR=7.983, p < 0.001) and radiotherapy (HR=0.606, p = 0.031) were independent prognostic factors affecting DSS. Conclusion: Based on SEER data analysis, male, high tumor grade, regional stage, metastasis stage and radiotherapy are independent predictors of poor survival of patients with spinal osteosarcoma. The clinical treatment of spinal osteosarcoma still faces serious challenges. Future research should focus on the clinical impact and survival outcomes of the emerging targeted and immune therapies for the sake of improving the survival stalemate of spinal osteosarcoma.

Surgical management and outcomes of spinal metastasis of malignant adrenal tumor: A retrospective study of six cases and literature review.

Purpose: Spinal metastasis of malignant adrenal tumor (SMMAT) is an extremely rare and poorly understood malignant tumor originating from the adrenal gland. The objective of this study is to elucidate the clinical characteristics and discuss surgical management and outcomes of SMMAT. Methods: Included in this study were six SMMAT patients who received surgical treatment in our center between February 2013 and May 2022. Their clinical data and outcomes were retrospectively analyzed to gain a better understanding of SMMAT. In addition, ten cases from the literature focusing on SMMAT were also reviewed. Results: Surgery was performed successfully, and the associated symptoms were relieved significantly in all patients postoperatively. The mean follow-up duration was 26.2 (range 3-55) months. Two patients died of tumor recurrence 12 and 48 months after operation respectively. The other four patients were alive at the last follow-up. Conclusions: The prognosis of SMMAT is usually poor. Preoperative embolization and early surgical radical resection can offer satisfactory clinical outcomes. The patient's health status, preoperative neurological function, tumor location and the resection mode are potential prognostic factors of SMMAT.

Study on the effect of artificial joint replacement for osteosarcoma.

Osteosarcoma is one of the most prevalent primary malignant bone tumors that affects teenagers more than adults. In recent years, artificial femoral replacement has become more and more common. The use of artificial total femoral replacement surgery prevents the need for amputating the damaged limb, preserves the patient's ability to move and bear weight on the leg, lessens the severity of the psychological trauma, and significantly raises the patient's quality of life. To explore the treatment methods and therapeutic effects of artificial femoral replacement in the treatment of femoral osteosarcoma. The clinical data of 11 patients with femoral malignant tumors who underwent artificial femoral replacement from January 2019 to March 2022 were retrospectively analyzed. Among them, 7 males and 4 females, 11 to 40 years old, average 19.36 ± 9.44 years old. The disease duration is 2 to 7 months, with an average of 4.7 months. Before and 3 months after operation, the patients who had tumors were given a score on the visual analog scale, and their quality of life was also measured. At the most recent follow-up, both the Musculoskeletal Tumor Society score and the Harris hip score were analyzed. Eleven patients were followed up for 6 to 58 months, and an average of 21 months. Complications such as wound infection, joint dislocation, and nerve damage did not occur. In 1 patient, popliteal vein thrombus formation, and in 2 patients with osteosarcoma died from tumor progression. Visual analog scale score at 3 months after surgery and the quality-of-life scores were 3.68 ± 1.39 and 40.04 ± 4.31, respectively, which were significantly improved compared to before surgery (5.94 ± 1.19 and 22.42 ± 3.63, respectively, P < .05). At the last interview, Musculoskeletal Tumor Society score is scored from 18 to 29 points, average 22.5 ± 5.9 points, and Harris hip score is scored from 42 to 90 points, with an average score of 69.0 ± 14.7. Artificial total femoral replacement is an effective limb salvage operation in the treatment of osteosarcoma.

Surgical management and outcome of Extra-adrenal myelolipomas at unusual locations: A report of 11 cases in a single center.

Purpose: Extra-adrenal myelolipomas (EAMs) are rare benign tumors composed of both mature adipose and hematopoietic tissues with unclear etiology. There have been only sporadic case reports about the clinical characteristics and management of EAMs. Here we present our experience and practice in the clinical diagnosis and treatment of 11 consecutive patients with EAMs. Method: We retrospectively reviewed 11 consecutive patients, who received surgeries in our department and were confirmed as having EAMs by postoperative histopathology from April 2016 to December 2021. Clinical information and follow-up data of all patients were collected and analyzed afterwards. Results: Of the 11 EAM patients (7 male and 4 female) with a mean age of 47.6 years, 3 were asymptomatic and 8 were symptomatic with a mean symptom duration of 6.07 months. EAMs were found in the thoracic spine in 4 cases, paravertebral mediastinal regions in 3 cases, ilium in 2 cases, humerus in 1 case, and rib in 1 case. All patients were initially misdiagnosed as other tumors by radiologists. All 11 patients received gross total excision or curettage with a mean intraoperative blood loss of 781.82 ± 1143.3 ml and a mean operation duration of 180.91 ± 98.41 min. Patients' Frankel scores and Karnofsky Performance Status score were improved or at least preserved postoperatively. No significant complications occurred postoperatively. All the 11 patients survived, and no local recurrence or distant metastasis occurred during the mean follow-up period of 42.0 months. Conclusion: The surgical outcome and prognosis of EAMs are excellent and surgery can serve as the method of radical treatment.

m6A-dependent upregulation of TRAF6 by METTL3 is associated with metastatic osteosarcoma.

OBJECTIVES: RNA N6-methyladenosine (m6A) is associated with tumorigenesis. The importance of methyltransferase-like 3 (METTL3) has been reported in cancer progression and metastasis. However, its role and molecular mechanism in osteosarcoma (OS), the most common primary bone tumor, is poorly studied. In this study, we aimed to investigate the functional role and underlying mechanism of METTL3 in the metastasis of OS. METHODS: The expression differences of METTL3 between metastatic and non-metastatic OS tissues and patients with different Enneking stages were detected using RT-qPCR. METTL3 was artificially downregulated in the cells, followed by wound healing assay, Matrigel assay, immunofluorescence, in vivo tumorigenic assay, HE staining, and western blot. Transcriptome sequencing and m6A-seq was conducted to identify the downstream genes of METTL3, and RIP and dual-luciferase assays were performed for validation. The expression of TRAF6 in OS tissues was detected using RT-qPCR. Finally, the rescue experiments were conducted. RESULTS: METTL3 was overexpressed in metastatic OS tissues, and downregulation of METTL3 decreased cell migration, invasion, epithelial-mesenchymal transition, and tumorigenic and metastatic activities. The m6A site was highly enriched in cells poorly expressing METTL3, and the m6A peak was mainly enriched in the exon region. METTL3 was positively correlated with TRAF6 in metastatic OS, and depletion of METTL3 resulted in the loss of TRAF6 expression in OS cells. Upregulation of TRAF6 contributed to metastases in vitro and in vivo. CONCLUSION: METTL3 is highly expressed in OS and enhances TRAF6 expression through m6A modification, thereby promoting the metastases of OS cells.

Development and Validation of a Scoring System for Differential Diagnosis of Tuberculosis and Metastatic Tumor in the Spine.

PURPOSE: Spinal tuberculosis (TB) and metastatic tumor (MT) are common diseases with similar manifestations. Although pathological evaluation is the gold standard to confirm diagnosis, performing biopsies in all patients is not feasible. This study is aimed to create a scoring system to facilitate the differential diagnosis of spinal TB and MT before invasive procedures. METHODS: Altogether, 447 patients with spinal TB (n=198) and MT (n=249) were retrospectively analyzed. Patients were randomly assigned at 2:1 ratio to a training cohort and a validation cohort. Clinical, laboratory, and radiological diagnostic factors were identified by χ2 and multiple logistic regression analyses. The scoring system was then established based on the identified independent diagnostic factors scored by regression coefficient ß value, with the cut-off value being determined by ROC curve. The sensitivity and specificity of the system was calculated by comparing the predicted diagnosis with their actual pathological diagnosis. RESULTS: This scoring system was composed of 5 items: pain worsens at night (0 or 2 points), CRP value (0 or 3 points), tumor marker values (0 or 2 points), skip lesions (0 or 3 points), and intervertebral space destruction (0 or 3 points). Patients scoring higher than 7.5 could be diagnosed as spinal TB, otherwise, MT. According to the internal validation, the sensitivity and specificity of the system were 87.9% and 91.6%, respectively. CONCLUSION: This study established and validated a scoring system which could be used to differentiate spinal TB from MT, thus helping clinicians in quick and accurate differential diagnosis.