[Retracted] MicroRNA-493 inhibits the proliferation and invasion of osteosarcoma cells through directly targeting specificity protein 1.

[This retracts the article DOI: 10.3892/ol.2018.8268.].

GALNT5 functions as a suppressor of ferroptosis and a predictor of poor prognosis in pancreatic adenocarcinoma.

Mucin-type O-glycosylation, a posttranslational modification of membrane and secretory proteins, facilitates metastasis and immune escape in tumor cells. N-acetylgalactosaminyl-transferase 5 (GALNT5), the enzyme initiating mucin-type O-glycosylation, is known to advance the progression of various tumors. Yet, the comprehensive role of GALNT5 in pan-cancer scenarios remains to be elucidated. In this research, we conducted a database-centric pan-cancer expression analysis of GALNT5. We examined its aberrant expression, assessed its prognostic implications, and explored the correlations between GALNT5 expression and factors such as ferroptosis, immune cell infiltration levels, and immune checkpoint gene expression across multiple tumor types. To substantiate GALNT5's role, we analyzed cell proliferation, migration, invasion, and ferroptosis in PAAD cells after GALNT5 knockdown. Additionally, RNA-seq was employed to discern potential downstream pathways influenced by GALNT5. Our findings indicate that GALNT5 expression is heightened in the majority of tumors, correlating with the prognosis of multiple cancers. There's a notable association between GALNT5 levels and ferroptosis-related genes, immune cell infiltration, and immune checkpoint genes. In PAAD specifically, the role of GALNT5 was further probed. Knockdown of GALNT5 curtailed the proliferation, migration, and invasion capacities of PAAD cells, concurrently promoting ferroptosis. Moreover, in vivo studies demonstrated that GALNT5 inhibition stunted PAAD tumor growth. The RNA-seq analysis unveiled inflammation and immune-centric pathways, such as the TNF signaling pathway, as potential downstream conduits of GALNT5. In conclusion, our pan-cancer study underscores GALNT5 as a potential therapeutic target for enhancing PAAD prognosis, given its strong ties with ferroptosis and immune cell infiltration. Our experiments further define GALNT5 as a novel suppressor of ferroptosis.

Identification of ARAP3 as a regulator of tumor progression, macrophage infiltration and osteoclast differentiation in a tumor microenvironment-related prognostic model of Ewing sarcoma.

Understanding the specificity and complexity of the tumor microenvironment (TME) of Ewing sarcoma (ES) is essential for identifying the immune characteristics of ES, improving the prediction of immunotherapeutic response, and facilitating therapeutic target discovery. In this study, we not only evaluated the gene sets associated with TME in ES using ESTIMATE and WGCNA algorithms based on the transcriptome data of ES, but also constructed a prognostic model (ES Score) using univariate Cox regression and Lasso regression and assessed its predictive ability on immune cell infiltration. Subsequently, we identified ARAP3 as a key gene affecting the TME of ES. In addition, bioinformatic analyses and in vitro experiments proved that the high expression of ARAP3 regulated ES cell proliferation, migration, as well as apoptosis via the p53 signaling pathway and affected macrophage infiltration and osteoclast differentiation through regulating IL1B and IL11 secretion of tumor cells.

Development and Validation of a Prognostic Model for Overall Survival in Patients with Primary Pelvis and Spine Osteosarcoma: A Population-Based Study and External Validation.

BACKGROUND: Primary pelvis and spine osteosarcoma (PSOS) is a specific type of osteosarcoma that is difficult to treat and has a poor prognosis. In recent years, the research on osteosarcoma has been increasing, but there have been few studies on PSOS; in particular, there have been a lack of analyses with a large sample size. This study aimed to construct and validate a model to predict the overall survival (OS) of PSOS patients, as currently there are no tools available for assessing their prognosis. METHODS: Data including demographic information, clinical characteristics, and follow-up information on patients with PSOS were collected from the Surveillance, Epidemiology, and End Results (SEER) database, as well as from the Spine Tumor Center of Changzheng Hospital. Variable selection was achieved through a backward procedure based on the Akaike Information Criterion (AIC). Prognostic factors were identified by univariate and multivariate Cox analysis. A nomogram was further constructed for the estimation of 1-, 3-, and 5-year OS. Calibration plots, the concordance index (C-index), and the receiver operating characteristic (ROC) were used to evaluate the prediction model. RESULTS: In total, 83 PSOS patients and 90 PSOS patients were separately collected from the SEER database and Changzheng Hospital. In the SEER cohort, liver metastasis, lung metastasis, and chemotherapy were recognized as independent prognostic factors for OS (p < 0.05) and were incorporated to construct the initial nomogram. However, the initial nomogram showed poor predictive accuracy in internal and external validation. Then, we shifted our focus to the Changzheng data. Lung metastasis involving segments, Eastern Cooperative Oncology Group (ECOG) performance score, alkaline phosphatase (ALP) level, and en bloc resection were ultimately identified as independent prognostic factors for OS (p < 0.05) and were further incorporated to construct the current nomogram, of which the bias-corrected C-index was 0.834 (0.824-0.856). The areas under the ROC curves (AUCs) of the current nomogram regarding 1-, 3-, and 5-year OS probabilities were 0.93, 0.96, and 0.92, respectively. CONCLUSION: We have developed a predictive model with satisfactory performance and clinical practicability, enabling effective prediction of the OS of PSOS patients and aiding clinicians in decision-making.

Clinical and Biomechanical Study of Laminoplasty for Thoracic and Lumbar Intradural Tumors.

(1) Background: Primary intraspinal tumors account for 2-15% of all central nervous system (CNS) tumors. Most intraspinal tumors are benign, and about 40% of them occur intradurally, for which early surgery is the preferred treatment. Laminectomy with pedicle screw fixation is the conventional surgical treatment. However, laminectomy with pedicle screw fixation is likely to reduce the spinal range of motion (ROM), with many other complications, although it can maintain the stability of the spine. The aim of this study is to determine whether laminoplasty as a new surgical approach for thoracic and lumbar intradural tumors is superior to laminectomy in preserving spinal ROM, maintaining spinal stability and reducing postoperative complications. (2) Methods: We retrospectively analyzed 50 patients who received intradural tumor resection, including 23 who received traditional laminectomy with pedicle screw fixation and 27 who received new laminoplasty. Spinal ROM was evaluated by lumbar flexion/extension radiograph and biomechanical evaluation. Spinal stability was evaluated by imaging observations of the spinal Cobb angle and laminar bone fusion. Postoperative complications were evaluated according to cerebrospinal fluid (CSF) leakage and the length of hospital stay. (3) Results: Compared with the laminectomy group, patients in the laminoplasty group exhibited a better spinal ROM (31.6 ± 12.0° vs. 21.7 ± 11.8°, p = 0.013), a smaller Cobb angle (9.6 ± 4.3 vs. 12.5 ± 5.3, p = 0.034), a lower incidence of CSF leakage (4/14.8% vs. 11/47.8%, p = 0.015), and a shorter length of hospital stay (13.1 ± 1.8 vs. 15.1 ± 2.3 days, p = 0.001). Most patients in the laminoplasty group had satisfactory bone fusion. The biomechanical experiment also demonstrated that spinal ROM in laminoplasty was larger than that in the laminectomy group. (4) Conclusions: Compared with the traditional surgery, the new laminoplasty surgery can better maintain the stability of the spine, preserve spinal ROM, and reduce postoperative complications. It is a surgical method that can be clinically popularized.

A novel molecular classification method for osteosarcoma based on tumor cell differentiation trajectories.

Subclassification of tumors based on molecular features may facilitate therapeutic choice and increase the response rate of cancer patients. However, the highly complex cell origin involved in osteosarcoma (OS) limits the utility of traditional bulk RNA sequencing for OS subclassification. Single-cell RNA sequencing (scRNA-seq) holds great promise for identifying cell heterogeneity. However, this technique has rarely been used in the study of tumor subclassification. By analyzing scRNA-seq data for six conventional OS and nine cancellous bone (CB) samples, we identified 29 clusters in OS and CB samples and discovered three differentiation trajectories from the cancer stem cell (CSC)-like subset, which allowed us to classify OS samples into three groups. The classification model was further examined using the TARGET dataset. Each subgroup of OS had different prognoses and possible drug sensitivities, and OS cells in the three differentiation branches showed distinct interactions with other clusters in the OS microenvironment. In addition, we verified the classification model through IHC staining in 138 OS samples, revealing a worse prognosis for Group B patients. Furthermore, we describe the novel transcriptional program of CSCs and highlight the activation of EZH2 in CSCs of OS. These findings provide a novel subclassification method based on scRNA-seq and shed new light on the molecular features of CSCs in OS and may serve as valuable references for precision treatment for and therapeutic development in OS.

A chronicle review of new techniques that facilitate the understanding and development of optimal individualized therapeutic strategies for chordoma.

Chordoma is a rare malignant bone tumor that mainly occurs in the sacrum and the clivus/skull base. Surgical resection is the treatment of choice for chordoma, but the local recurrence rate is high with unsatisfactory prognosis. Compared with other common tumors, there is not much research and individualized treatment for chordoma, partly due to the rarity of the disease and the lack of appropriate disease models, which delay the discovery of therapeutic strategies. Recent advances in modern techniques have enabled gaining a better understanding of a number of rare diseases, including chordoma. Since the beginning of the 21st century, various chordoma cell lines and animal models have been reported, which have partially revealed the intrinsic mechanisms of tumor initiation and progression with the use of next-generation sequencing (NGS) techniques. In this study, we performed a systematic overview of the chordoma models and related sequencing studies in a chronological manner, from the first patient-derived chordoma cell line (U-CH1) to diverse preclinical models such as the patient-derived organoid-based xenograft (PDX) and patient-derived organoid (PDO) models. The use of modern sequencing techniques has discovered mutations and expression signatures that are considered potential treatment targets, such as the expression of Brachyury and overactivated receptor tyrosine kinases (RTKs). Moreover, computational and bioinformatics techniques have made drug repositioning/repurposing and individualized high-throughput drug screening available. These advantages facilitate the research and development of comprehensive and personalized treatment strategies for indicated patients and will dramatically improve their prognoses in the near feature.

Identification of ATG7 as a Regulator of Proferroptosis and Oxidative Stress in Osteosarcoma.

Background: Ferroptosis has gained significant attention from oncologists as a vital outcome of oxidative stress. The aim of this study was to develop a prognostic signature that was based on the ferroptosis-related genes (FRGs) for osteosarcoma patients and explore their specific role in osteosarcoma. Methods: The training cohort dataset was extracted from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. Different techniques like the univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, multivariate Cox regression analyses, and the Kaplan-Meier (KM) survival analyses were utilized to develop a prognostic signature. Then, the intrinsic relationship between the developed gene signature and the infiltration levels of the immune cells was further investigated. An external validation dataset from the Gene Expression Omnibus (GEO) database was employed to assess the predictive ability of the developed gene signature. Subsequently, the specific function of potential FRG in affecting the oxidative stress reaction and ferroptosis of osteosarcoma cells was identified. Results: A prognostic signature based on 5 FRGs (CBS, MUC1, ATG7, SOCS1, and PEBP1) was developed, and the patients were classified into the low- and high-risk groups (categories). High-risk patients displayed poor overall survival outcomes. The risk level was seen to be an independent risk factor for determining the prognosis of osteosarcoma patients (p < 0.001, hazard ratio: 7.457, 95% CI: 3.302-16.837). Additionally, the risk level was associated with immune function, which might affect the survival status of osteosarcoma patients. Moreover, the findings of the study indicated that the expression of ATG7 was related to the regulation of oxidative stress in osteosarcoma. Silencing the ATG7 gene promoted the proliferation and migration in osteosarcoma cells, suppressing the oxidative stress and ferroptosis process. Conclusions: A novel FRG signature was developed in this study to predict the prognosis of osteosarcoma patients. The results indicated that ATG7 might regulate the process of oxidative stress and ferroptosis in osteosarcoma cells and could be used as a potential target to develop therapeutic strategies for treating osteosarcoma.

PTBP1 as a Promising Predictor of Poor Prognosis by Regulating Cell Proliferation, Immunosuppression, and Drug Sensitivity in SARC.

Background: Sarcomas (SARC) have been found as rare and heterogeneous malignancies with poor prognosis. PTBP1, belonging to the hnRNPs family, plays an essential role in some biological functions (e.g., pre-mRNA splicing, cell growth, and nervous system development). However, the role of PTBP1 in SARC remains unclear. In this study, the aim was to investigate the potential role of PTBP1 with a focus on SARC. Methods: The expression, prognostic value, possible biological pathways of PTBP1, and its relationship with immune infiltration and drug sensitivity were comprehensively analyzed based on multiple databases. PTBP1 was further validated in osteosarcoma as the most prominent bone SARC. The expression of PTBP1 was investigated through IHC. The prognostic value of PTBP1 was verified in TARGET-OS databases. CRISPR/Cas9-mediated PTBP1 knockout HOS human osteosarcoma cell lines were used to assess the effect of PTBP1 on cell proliferation, migration, metastasis and cell cycle by CCK-8, Transwell migration, invasion, and FACS experiment. Result: PTBP1 was highly expressed and significantly correlated with poor prognosis in several cancers, especially in SARC, which was validated in the clinical cohort and osteosarcoma cell lines. The genetic alteration of PTBP1 was found most frequently in SARC. Besides, PTBP1 played a role in oncogenesis and immunity through cell cycle, TGFB, autophagy, and WNT pathways at a pan-cancer level. Knockout of PTBP1 was observed to negatively affect proliferation, migration, metastasis, and cell cycle of osteosarcoma in vitro. Furthermore, PTBP1 was significantly correlated with tumor immune infiltration, DNA methylation, TMB, and MSI in a wide variety of cancers. Moreover, the potential of the expression level of PTBP1 in predicting drug sensitivity was assessed. Conclusions: PTBP1 is highly expressed and correlated with prognosis and plays a vital pathogenic role in oncogenesis and immune infiltration of various cancers, especially for SARC, which suggests that it may be a promising prognostic marker and therapeutic target in the future.

Single-Cell RNA-Sequencing Analyses Revealed Heterogeneity and Dynamic Changes of Metabolic Pathways in Astrocytes at the Acute Phase of Ischemic Stroke.

Astrocyte plays important roles in the pathogenesis of ischemic stroke and reperfusion injury. They intensively participate in the energy metabolism of the brain, while their heterogeneity and function after ischemic stroke remain controversial. By employing single-cell sequencing of mice cortex at 12 h after transient middle cerebral artery occlusion (tMCAO) and comparing with the similar published datasets of 24h after tMCAO, we uncover the cellular phenotypes and dynamic change of astrocytes at the acute phase of ischemic stroke. In this study, we separately identified 3 major subtypes of astrocytes at the 12 h-tMCAO-system and 24 h-tMCAO-system, indicated the significant differences in the expression of genes and metabolic pathways in the astrocytes between the two time nodes after ischemic stroke, and detected the major change in the energy metabolism. These results provided a comprehensive understanding of the characteristic changes of astrocytes after ischemic stroke and explored the potential astrocytic targets for neuroprotection.

Heterogeneity of tumor microenvironment is associated with clinical prognosis of non-clear cell renal cell carcinoma: a single-cell genomics study.

Non-clear renal cell carcinomas (nccRCCs) are less frequent in kidney cancer with histopathological heterogeneity. A better understanding of the tumor biology of nccRCC can provide more effective treatment paradigms for different subtypes. To reveal the heterogeneity of tumor microenvironment (TME) in nccRCC, we performed 10x sing-cell genomics on tumor and normal tissues from patients with papillary renal cell carcinoma (pRCC), chromophobe RCC (chrRCC), collecting duct carcinoma (CDRCC) and sarcomatoid RCC (sarRCC). 15 tissue samples were finally included. 34561 cells were identified as 16 major cell clusters with 34 cell subtypes. Our study presented the sing-cell landscape for four types of nccRCC, and demonstrated that CD8+ T cells exhaustion, tumor-associated macrophages (TAMs) and sarcomatoid process were the pivotal factors in immunosuppression of nccRCC tissues and were closely correlated with poor prognosis. Abnormal metabolic patterns were present in both cancer cells and tumor-infiltrating stromal cells, such as fibroblasts and endothelial cells. Combined with CIBERSORTx tool, the expression data of bulk RNA-seq from TCGA were labeled with cell types of our sing-cell data. Calculation of the relative abundance of cell types revealed that greater proportion of exhausted CD8+ T cells, TAMs and sarRCC derived cells were correlated with poor prognosis in the cohort of 274 nccRCC patients. To the best of our knowledge, this is the first study that provides a more comprehensive sight about the heterogeneity and tumor biology of nccRCC, which may potentially facilitate the development of more effective therapies for nccRCC.

Identifying the Risk Factors and Estimating the Prognosis in Patients with Pelvis and Spine Ewing Sarcoma: A Population-Based Study.

STUDY DESIGN: Retrospective analysis. OBJECTIVE: The study was designed to: (1) figure out risk factors of metastasis; (2) explore prognostic factors and develop a nomogram for pelvis and spine Ewing sarcoma (PSES). SUMMARY OF BACKGROUND DATA: Tools to predict survival of PSES are still insufficient. Nomogram has been widely developed in clinical oncology. Moreover, risk factors of PSES metastasis are still unclear. METHODS: The data were collected and analyzed from the Surveillance, Epidemiology, and End Results (SEER) database. The optimal cutoff values of continuous variables were identified by X-tile software. The prognostic factors of survival were performed by Kaplan-Meier method and multivariate Cox proportional hazards modeling. Nomograms were further constructed for estimating 3- and 5-year cancer-specific survival (CSS) and overall survival (OS) by using R with rms package. Meanwhile, Pearson χ2 test or Fisher exact test, and logistic regression analysis were used to analyze the risk factors for the metastasis of PSES. RESULTS: A total of 371 patients were included in this study. The 3- and 5-year CSS and OS rate were 65.8 ±â€Š2.6%, 55.2 ±â€Š2.9% and 64.3 ±â€Š2.6%, 54.1 ±â€Š2.8%, respectively. The year of diagnosis, tumor size, and lymph node invasion were associated with metastasis of patients with PSES. A nomogram was developed based on identified factors including: age, tumor extent, tumor size, and primary site surgery. The concordance index (C-index) of CSS and OS were 0.680 and 0.679, respectively. The calibration plot showed the similar trend of 3-year, 5-year CSS, and OS of PSES patients between nomogram-based prediction and actual observation, respectively. CONCLUSION: PSES patients with earlier diagnostic year (before 2010), larger tumor size (>59 mm), and lymph node invasion, are more likely to have metastasis. We developed a nomogram based on age, tumor extent, tumor size, and surgical treatments for determining the prognosis for patients with PSES, while more external patient cohorts are warranted for validation.Level of Evidence: 3.

Prognostic Significance of a Novel Score Model Based on Preoperative Indicators in Patients with Breast Cancer Spine Metastases (BCSM).

BACKGROUND: Surgery remains the mainstay of treatment for breast cancer spinal metastasis (BCSM) to relieve symptoms and improve the quality of life of BCSM patients. Therefore, it is important to effectively predict the prognosis of patients to determine whether they can undergo surgical operation. However, the prevalent methods for prognosis evaluation lack specificity and sensitivity for indicated malignancies like breast cancer because they are built on a relatively small number of heterogeneous types of primary tumors. The aim of the present study was to explore a novel predictive model based on the clinical, pathological and blood parameters obtained from BCSM patients before they received surgical intervention. METHODS: Altogether, 144 patients were included in this study. Univariate and multivariate analyses were performed to investigate the significance of preoperative parameters and identify independent factors for prognostic prediction of BCSM. A nomogram for survival prediction was then established and validated. Time-dependent ROC (TDROC) curves were graphed to evaluate the accuracy of the novel model vs other scoring systems including Tomita Score, revised Tokuhashi Score, modified Bauer Score and New England Spinal Metastasis Score. P values <0.05 were considered statistically significant. RESULTS: Independent factors, including preoperative postmenopausal (P=0.034), visceral metastasIs (P=0.021), preoperative Frankel Score (P=0.001), estrogen receptor status (P=0.014), platelet-to-lymphocyte ratio (P=0.012), lymphocyte-monocyte ratio (P<0.001) and albumin-globulin ratio (P=0.017), were selected into the nomogram model with the C-index of 0.834 (95% CI, 0.789-0.890). TDROC curves showed that the Changzheng Hospital (CZ) Score system had the best performance and exhibited the largest IAUC value in comparison with the other scoring systems. CONCLUSION: We constructed a nomogram model known as CZ Score based on the significant factors to predict the prognosis for BCSM patients. The result showed that CZ Score had a better value for prognostic evaluation and surgical decision-making as compared with the other scoring systems.

NAT1 promotes osteolytic metastasis in luminal breast cancer by regulating the bone metastatic niche via NF-κB/IL-1B signaling pathway.

Breast cancer is a molecularly heterogeneous disease that can be subdivided into different subtypes. Compared with the other subtypes, luminal breast cancer (LBC) is considered more susceptible to bone metastasis. However, the intrinsic mechanisms remain elusive. Bioinformatics analysis of the preset study showed that N-acetyltransferase 1 (NAT1) was specifically expressed in LBC and closely correlated with bone metastasis. In addition, NAT1 could promote LBC cell migration and clonal formation, induce osteoclast differentiation and raise the Rankl/Opg ratio in osteoblasts. Our in vivo experiment demonstrated that NAT1 promoted LBC bone metastasis and bone destruction, which could be reversed by NAT1 inhibitor treatment. The result of cytokine array showed that NAT1 could significantly over activate the NF-κB signaling pathway and up-regulate the expression of IL-1B, which further worked as downstream factors in these processes. All these results demonstrated NAT1 was up-regulated in LBC and promoted the formation of bone metastatic niche and osteolytic bone metastasis through the NAT1/NF-κB/IL-1B axis. This finding may provide a new pathway to help understand the mechanisms of LBC bone metastasis and suggest a novel therapeutic and diagnostic target for its treatment.

Prognostic Significance of Preoperative Inflammatory Biomarkers and Traditional Clinical Parameters in Patients with Spinal Metastasis from Clear Cell Renal Cell Carcinoma: A Retrospective Study of 95 Patients in a Single Center.

PURPOSE: The purpose of this retrospective study was to identify preoperative inflammatory biomarkers and clinical parameters and evaluate their prognostic significance in patients with spinal metastasis from clear cell renal cell carcinoma (CCRCC). PATIENTS AND METHODS: Correlations of overall survival (OS) with traditional clinical parameters and inflammatory indicators including the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), albumin-globulin ratio (AGR), and C-reactive protein to albumin ratio (CRP/Alb ratio) were analyzed in 95 patients with spinal metastasis from CCRCA using the Kaplan-Meier method to identify potential prognostic factors. Factors with P values ≤ 0.1 were subjected to multivariate analysis by Cox regression analysis. P values ≤ 0.05 were considered statistically significant. RESULTS: The 95 patients included in this study were followed up by a mean of 48.8 months (median 51 months; range 6-132 months), during which 21 patients died, with a death rate of 22.1%. The statistical results indicated that patients with total piecemeal spondylectomy (TPS), targeted therapy, NLR < 3.8 and PLR < 206.9 had a significantly longer OS rate. CONCLUSION: TPS and targeted therapy could significantly prolong the OS of patients with spinal metastasis from CCRCC. In addition, NLR and PLR are robust and convenient prognostic indicators that have a discriminatory ability superior to other inflammatory biomarkers.

Application of Individualized 3D-Printed Artificial Vertebral Body for Cervicothoracic Reconstruction in a Six-Level Recurrent Chordoma.

AIM: To present the surgical planning, manufacturing and implantation of an individualized 3D-printed prosthesis for cervicothoracic reconstruction in a six-level recurrent chordoma. MATERIAL AND METHODS: A 40-year-old female patient with recurrent cervicothoracic chordoma was admitted in our center. Onestage tumorectomy was performed using the combined anterior and posterior approach, and a customized 3D-printed prosthesis was anatomically installed on the defect with vertebral screws from C2 to T2. RESULTS: The whole procedure took 13 hours, and intraoperative blood loss was 7500 mL. The patient recovered uneventfully, and symptoms of pain and weakness of right upper extremity were significantly diminished postoperatively. No local recurrence was found during 9-month follow-up, and no subsidence, displacement or fracture of the prosthesis was observed radiographically. CONCLUSION: To the best of our knowledge, this is the first report of biomechanical reconstruction using an individualized 3D-printed artificial vertebral body in a six-level recurrent chordoma. Customized design of the prosthesis helps to address the difficulty in fixation and simplify the surgical procedure. In the spinal transition point where solid fusion is hard to achieve, an individualized 3D-printed implant may exhibit excellent primary stability. Accordingly, this study believes that such burgeoning technique shows a promising prospect in complicated spinal oncology surgery.

Surgical Management and Factors Affecting the Prognosis for Patients with Thyroid Cancer Spinal Metastases: A Retrospective Analysis of 52 Consecutive Patients from a Single Center.

BACKGROUND: Thyroid cancer, one of the most common endocrine malignancies in developed areas and China, is associated with favorable prognosis. However, the presence of spinal metastases will remarkably reduce the life expectancy for patients with thyroid cancer. In addition, limited information is available about such disease. METHODS: Various potential clinical factors were submitted to univariate and multivariate analyses to identify the independent variables that predicted the prognosis for patients. In addition, the survival rate was estimated according to the Kaplan-Meier method, and statistic differences were calculated by the log-rank test. Moreover, factors with a P value of ≤0.1 were performed multivariate analysis using a multivariate Cox proportional hazards model, and factors with a P value of <0.05 were considered as statistically significant. RESULTS: Seven potential independent prognostic factors had been identified through univariate analysis, which were then subjected to multivariate analysis. Our results suggested that age of ≤50 years, single segment involved, and follicular thyroid cancer were the independent favorable prognostic factors. CONCLUSIONS: Findings in this study indicate that age of ≤50 years, single segment involved, and follicular thyroid cancer are favorable prognostic factors for patients with thyroid cancer spinal metastases.

Prognostic factors of patients with spinal malignant melanoma after surgical intervention: a case series of 21 patients and literature review.

BACKGROUND: Spinal malignant melanoma (SMM) is a rare type of tumor that can cause nerve roots or spinal cord compression. Patients often suffer from fierce pain and paralyzation. And the estimated survival time were less than 6 months. Surgical interventions to remove the tumor and decompress the nearby nerve roots and spinal cord are effective management. Unfortunately, there lack a thorough and persuasive surgical guideline that specifically aims for this disease. It is necessary to obtain some clinical prognostic factors that predict the recurrence rate and overall survival (OS) of patients with SMM who underwent surgical interventions. METHODS: 21 patients with SMM who underwent surgical intervention were retrospectively reviewed. Related patients factors, treatment factors and tumor factors were acquired and subjected into survive analyses using Kaplan-Meier method and the log-rank test. Further Cox proportional hazards model was used to identify independent prognostic factors. Literature regarding surgical interventions on SMM patients were reviewed and summarized as well. RESULTS: Surgical approach total en-bloc spondylectomy (TES/Piecemeal) (p = 0.015, B 0.029, 95%CI 0.002-0.508), preoperative Frankel grade (A-C/D-E) (p = 0.021, B 15.041, 95%CI 1.492-151.669) and tumor metastases (Yes/No) (p = 0.013, B 16.667, 95%CI 1.805-153.897) are independent prognostic factors for recurrence free survival (RFS). Preoperative Frankel grade (A-C/D-E) (p = 0.031, B 10.676, 95%CI 1.241-91.877) is independent prognostic factors for OS. 12 literatures have been reviewed, including 11 case reports and one retrospective study. CONCLUSIONS: Surgical interventions for patients with SMM are beneficial. Surgical approach (TES/piecemeal), tumor origin (primary/metastasis) and preoperative Frankel grade (A-C/D-E) are independent risk factors in predicting RFS. Preoperative Frankel grade (A-C/D-E) is independent prognostic factor in predicting OS.

SOSTDC1 inhibits bone metastasis in non-small cell lung cancer and may serve as a clinical therapeutic target.

Bone metastasis occurs in ~40% patients with non­small cell lung cancer (NSCLC), resulting in serious morbidity and mortality. Sclerostin domain­containing protein 1 (SOSTDC1) has been demonstrated to be associated with the development and progression of multiple types of cancer. However, the role of SOSTDC1 in NSCLC bone metastasis remains unclear. In the present study, it was identified that SOSTDC1 was downregulated in NSCLC bone metastatic lesions compared with that in primary tumors, and low SOSTDC1 expression predicted poor prognosis for patients with NSCLC. Functionally, SOSTDC1 overexpression suppressed NSCLC cell proliferation, migration, invasion and cancer cell­induced osteoclastogenesis, while SOSTDC1 knockdown produced the opposite effect. In addition, a number of potential downstream target genes of SOSTDC1, which were demonstrated to be associated with tumor progression and bone metastasis, were identified in NSCLC cells by RNA deep sequencing and RT­qPCR assays. The results from the present study may provide useful insight for an improved understanding of the pathogenesis of NSCLC bone metastasis, and suggest that SOSTDC1 may be a potential prognostic biomarker and therapeutic target for NSCLC bone metastasis.

MicroRNA-493 inhibits the proliferation and invasion of osteosarcoma cells through directly targeting specificity protein 1.

Osteosarcoma (OS) is the most common type of primary bone tumor and accounts for ~60% of all malignant bone tumors in children and adolescents. A large number of studies have proposed that the dysregulated and dysfunctional microRNAs may serve important roles in the occurrence, progression and metastasis of various types of human cancer, including OS. MicroRNA-493 (miR-493) has been identified to act as a tumor suppressor in several types of human cancer. However, little is known regarding the expression pattern and clinical significance of miR-493 in OS. In the present study, reverse transcription-quantitative polymerase chain reaction analysis revealed that miR-493 was markedly downregulated in OS tissues and cell lines and a low miR-493 level were associated with distant metastasis and clinical stage. Furthermore, functional experiments demonstrated that enforced expression of miR-493 led to a significant decrease in OS cell proliferation and invasion in vitro. Furthermore, through bioinformatics analysis, specificity protein 1 (SP1) was identified as a direct target gene of miR-493 in OS. Its expression was upregulated in OS tissues and was negatively associated with miR-493 expression levels. Inhibition of SP1 expression also suppressed the proliferation and invasion of OS, exerting a similar effect to that induced by miR-493 overexpression. These results suggested that miR-493 inhibited OS cell proliferation and invasion through negative regulation of SP1. Therefore, miR-493/SP1 may represent a potential therapeutic target for the treatment of OS.