Introduction:Artificial intelligence (AI) chatbots has been well studied in many common diseases. However, little was reported for chordoma, which is a rare disease with high rates of recurrence, disability, and mortality. Research question:This study aims to assess the performance of oncologists and state-of-the-art AI chatbots in response to frequently-asked questions (FAQs) of chordoma from real world. The response performance was mainly evaluated by overall quality, empathy, and readability. Material and methods:Sixty chordoma-related FAQs, collected from social media, were addressed by various chatbots and oncologists, and the best-performing chatbot-generated text was further edited and assessed again. Rated scores were ordered for quality and empathy in a blind way. The readability was measured objectively by calculating Flesch-Kincaid Grade Level (FKGL), Automated Readability Index (ARI), and Gunning-Fog Index (GFI). Results:AI chatbots were universally superior to oncologists in response quality (3.86 ± 0.14 vs. 3.12 ± 0.25, p < 0.001) and empathy (3.28 ± 0.41 vs. 2.95 ± 0.48, p < 0.001). DeepSeek-R1 achieved highest rated score in response quality (4.20 ± 0.22), while Claude 3.5 Sonnet was considered as the best chatbots by comprehensive assessments. The chatbot drafted responses were easier to understand from patient's perspective (p < 0.001). Improved response quality (4.09 ± 0.12, p < 0.001), empathy (4.00 ± 0.39, p < 0.001), and readability (FKGL: 11.30 ± 2.42, p < 0.001) were obtained after editing the Claude-3.5-generated responses by oncologists. Discussion and conclusions:AI chatbots reached favorable quality and empathetic performance in response to chordoma-related FAQs, and generated equivalent readability compared to oncologists. With generative chatbot's assistance, oncologists may response more comprehensively and efficiently in addressing chordoma patient's common inquiries.

Ewing sarcoma (ES) is an aggressive malignancy with high metastatic potential and poor prognosis, necessitating novel biomarkers and therapeutic targets. This study investigates the role of the ubiquitin-activating enzyme E1 (UBA1) in ES pathogenesis and its clinical relevance. Bioinformatic analysis of GEO datasets was performed. UBA1 expression was validated in clinical samples and ES cell lines (A673, RDES) via Western blot and qPCR. To investigate the functional role and therapeutic potential of UBA1 in ES, we performed siRNA-mediated knockdown followed by a series of in vitro functional assays, including assessments of proliferation, colony formation, migration, invasion, cell cycle distribution, and EdU incorporation. Mechanistic studies were subsequently conducted through the WB experiment. In vivo experiments were carried out using a xenograft mouse model to evaluate the effect of UBA1 depletion on tumor growth. Additionally, the UBA1-specific inhibitor TAK-243 was used to assess the therapeutic potential of targeting UBA1. UBA1 expression was significantly elevated in ES tissues, and high UBA1 levels correlated with poor prognosis. Knockdown of UBA1 suppressed malignant phenotypes, including proliferation, colony formation, migration, and invasion, while inducing cell cycle arrest and inhibiting DNA synthesis. Mechanistically, UBA1 depletion led to dysregulation of the G2/M checkpoint pathway, consistent with Gene Set Enrichment Analysis (GSEA) predictions. In vivo experiments confirmed the oncogenic role of UBA1, and treatment with the UBA1 inhibitor TAK-243 recapitulated the effects observed upon UBA1 knockdown. Targeting UBA1 disrupts cell cycle progression and inhibits proliferation in ES, underscoring its therapeutic potential.

PURPOSE:Limited efficacy of current treatments for chordoma calls for novel therapeutic options. Combination of immune checkpoint inhibitors and antiangiogenic drugs has altered the landscape of cancer treatment but has rarely been investigated in chordoma. METHODS:An investigator-initiated, single-center, phase II trial was conducted on camrelizumab (a PD-1 inhibitor, 200 mg once every 2 weeks) plus apatinib (an antiangiogenic drug, 250 mg and 500 mg on alternate days, that is, 250 mg one day, 500 mg the next day, alternating) in patients with refractory chordoma for 4-week cycles. The primary end point was the objective response rate (ORR) per RECIST version 1.1. Secondary end points included ORR per Choi criteria, progression-free survival (PFS), overall survival, the disease control rate, median duration of response (mDoR), safety, and quality of life. The trial is registered with Chictr.org.cn (ChiCTR2100042938). RESULTS:Of the 38 patients initially screened between September 2021 and October 2024, 33 were enrolled. Median follow-up duration was 20.8 months (IQR, 13.35-26.55). ORR was 24.2% (8/33 [95% CI, 11.1 to 42.3]) per RECIST 1.1 and 48.5% (16/33 [95% CI, 30.8 to 66.5]) per Choi criteria. The median PFS was 28.4 months (95% CI, 13.53 to 43.28). The mDoR was not reached per RECIST 1.1 and was 22.2 months (95% CI, 12.5 to not reached) per Choi criteria. CDKN2A copy-number deletion or homozygous deletion was found to associate with worse prognosis. The most common grade 3 or 4 treatment-related adverse events included increased aspartate aminotransferase (13 [39.4%]) and increased alanine aminotransferase (11 [33.3%]). No treatment-related deaths occurred. CONCLUSION:Combination of camrelizumab and apatinib offered encouraging efficacy with manageable toxicity in chordoma treatment. CDKN2A alterations are associated with worse prognosis and may prove to be a potential biomarker for treatment selection.

Ewing sarcoma (ES) is an aggressive bone tumor in children and adolescents, and metastatic dissemination remains the major cause of treatment failure. Protocadherin 17 (PCDH17), a member of the cadherin superfamily, has been reported to exert context-dependent roles in solid tumors, but its significance in ES is unclear. Here, we analyzed Gene Expression Omnibus (GEO) datasets to evaluate PCDH17 expression, its association with overall survival and event-free survival, and the enrichment of biological pathways related to PCDH17 levels, and further examined PCDH17 expression in ES cell lines. The biological functions of PCDH17 were investigated using short hairpin RNA–mediated knockdown in A673 and RD-ES cells, followed by Cell counting kit-8 (CCK-8), colony formation, wound healing and transwell invasion assay, as well as western blotting (WB) and immunofluorescence (IF). PCDH17 was markedly upregulated in ES tissues and cell lines compared with normal counterparts, and high expression correlated with shorter survival. Gene set enrichment analysis (GSEA) indicated that high PCDH17 expression is associated with transcriptional programs driving cell cycle progression and oncogenic growth. Functionally, silencing PCDH17 significantly impairs proliferation, colony formation, migration and invasion of ES cells, and attenuates mesenchymal marker expression as well as associated morphological features. Collectively, our data indicate that PCDH17 is upregulated in ES and associated with worse survival, and that PCDH17 depletion suppresses malignant phenotypes in vitro. Together, these results nominate PCDH17 as a candidate prognostic biomarker and potential therapeutic target, which merits further validation.

Synovial sarcoma (SS) is a rare soft-tissue malignancy, with spinal involvement being exceptionally uncommon and associated with poor prognosis. Due to limited data, prognostic factors for spinal SS remain unclear. This study aimed to analyze clinical outcomes and identify prognostic indicators in spinal SS. We conducted a retrospective review of 46 SS patients (36 spinal, 10 extremity) treated at our center (2010–2022). Clinical, radiological, and pathological data were analyzed. Treatment strategies included surgical resection (en-bloc where feasible), chemotherapy, and radiotherapy. Bone invasion was assessed via imaging. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were evaluated using Cox regression and Kaplan-Meier analysis. Spinal SS exhibited frequent bone invasion (25/36 cases), a feature rare in extremity SS. The 5-year PFS and OS rates were 33.2

Spinal angiosarcoma (AS) is rare, with limited understanding of its therapeutic outcomes and prognostic factors. This study aimed to evaluate the impact of surgery and adjuvant treatments on the prognosis of patients with primary and metastatic spinal AS, as well as potential prognostic factors affecting spinal AS patients. A retrospective review was conducted on 29 consecutive patients with spinal AS at our center from 2014 to 2023. We divided spinal AS patients into primary and metastatic groups, and analyzed the effects of surgical methods, along with adjuvant chemotherapy and radiotherapy, in the prognosis of the two groups. Additionally, the prognostic factors for progression-free survival (PFS) and overall survival (OS) were analyzed by using the univariate and multivariate analyses in spinal AS patients. In isolated primary spinal AS patients, the 5-year OS and PFS rates were 47.9

11503 Background: The limited efficacy of current treatments for chordoma underscores the need for novel therapeutic options. Immune checkpoint inhibitors (ICI) have changed the landscape of cancer treatment but are rarely investigated for chordomas. Additionally, no established biomarkers reliably predict the efficacy of ICI and targeted therapies in this context. Methods: This investigator-initiated, single-arm, phase 2 trial evaluated the efficacy and safety of camrelizumab (anti-programmed death 1, PD-1) combined with apatinib (a tyrosine kinase inhibitor) in patients with advanced or refractory chordoma. Eligible patients received camrelizumab (200 mg intravenously every 2 weeks) and apatinib (250/500 mg orally daily) in 28-day cycles. The primary endpoint was objective response rate (ORR) assessed per RECIST 1.1 and Choi criteria. Secondary endpoints were median progression-free survival (PFS), overall survival, disease control rate (DCR) and safety. Next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH) were used to explore predictive biomarkers. The trial is registered on Chictr.org.cn (ChiCTR2100042938). Results: Between September 2021, and October 2024, 38 patients were screened, and 33 were enrolled for efficacy and safety analyses. The median treatment duration was 7 months (IQR 4-14), with a median radiologic evaluation time of 10 months (IQR 9-13) and median follow-up of 15 months (IQR 9-22). At data cutoff, 15 (45.5%) patients remained on treatment. Per RECIST 1.1, seven patients (21.2%, [95% CI, 9.0-38.9]) achieved partial response (PR), with a 6-month DCR of 85.2% (23/27). The median PFS was 18.1 months (95% CI, 11.0-28.5). According to Choi criteria, 16 patients (48.5%, [95% CI, 30.8-66.5]) achieved PR, with a 6-month DCR of 77.7% (21/27) and a median PFS of 15.3 months (95% CI, 10.6-NE). Two patients died of tumor progression, and two others with cervical recurrent chordoma died from postoperative complications. NGS analyses revealed copy number deletion (CND) of CDKN2A in 30% (6/20) of cases. Post hoc FISH analysis of 25 specimens identified homozygous deletion (HD) of CDKN2A in 40.0% (10/25), which correlated with poorer outcomes. Adverse events (AEs) occurred in 93.9% (31/33) of patients, with grade 3/4 AEs in 48.5%. Treatment-related AEs led to apatinib dose interruptions in 39.4% and camrelizumab interruptions in 21.2%. Conclusions: The combination of camrelizumab and apatinib demonstrated promising efficacy and manageable toxicity in chordoma treatment. Furthermore, CDKN2A alterations (CND or HD) were associated with poorer outcomes, providing a potential biomarker for therapeutic stratification. Clinical trial information: ChiCTR2100042938 .

Background and Objective:Unilateral biportal endoscopy (UBE) has been developing rapidly in coincidence with the popularization of minimally invasive spine surgery (MISS). However, the clinical outcome and invasiveness of UBE-assisted spinal surgery (UBESS) are undefined. The aim of the present study was to summarize the clinical outcome and surgical invasiveness of UBE for the treatment of various spinal degenerative diseases in a single center to validate the safety and application value of UBESS. Methods:Included in this study were 105 patients who received UBESS from November 2021 to June 2022 in our center. All patients were followed up postoperatively for at least 12 months. All basic information was recorded to depict the demographic and surgical variables. Clinical outcomes were assessed in terms of the operation time, complications, days of hospital stay, total blood loss, intraoperative blood loss, postoperative drainage volume, hidden blood loss, biochemical changes associated with surgical injury, comparison of the visual analogue scale (VAS) for back and leg pain, Japanese Orthopedic Association (JOA) scores for cervical diseases at preoperative and postoperative stage, as well as Oswetry Disability Index (ODI), and modified MacNab scores one year after treatment. Results:Of the 105 included patients, 68 patients were with single-level lumbar degenerative diseases, 22 with two-level diseases, two with three-level diseases, 10 with single-level isthmic spondylolisthesis, and three with single-level cervical spondylotic radiculopathy. UBE was performed by using five surgical approaches. The operation time, days of hospital stay, blood loss, postoperative immobilization time and prognosis were all estimated in consideration of the surgical approaches and the number of operated segments. The mean operation time ranged from 80 min to 214 min for single-level spinal diseases, and 112 min to 330 min for two-level ones. Total blood loss was higher in multilevel spinal surgery and single-level UBE-assisted lumbar interbody fusion+discectomy (ULIFD). The postoperative immobilization duration was between 0.5 and 2 days for single level spinal diseases, 1 and 3 days for 2-level diseases, fewer than 2 days for three-level diseases, and 1.5-12 days for isthmic spondylolisthesis (IS). The VAS and ODI for lumbar diseases decreased significantly and the JOA scores for cervical diseases improved after operation. The satisfaction rate was 89.70%, 85.71%, 90.00%, 66.67%, and 90.00% for the five surgical approaches respectively. Conclusions:UBESS has proved to be a safe, reliable and minimally invasive option for spinal degenerative diseases, with significant benefits of pain control, rapid functional recovery, short hospitalization, and early rehabilitation. However, postoperative hidden blood loss should be put under the careful management when performing UBESS.

Background/Objectives: Bone metastasis is a common and severe complication of lung adenocarcinoma (LUAD), impacting prognosis and treatment outcomes. Understanding the molecular mechanisms behind LUAD bone metastasis (LUADBM) is essential for developing new therapeutic strategies. The interactions between long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in the competing endogenous RNA (ceRNA) network are crucial in cancer progression and metastasis, but the regulatory mechanisms in LUADBM remain unclear. Methods: Microarray analysis was performed on clinical samples, followed by weighted gene co-expression network analysis (WGCNA) and construction of a ceRNA network. Molecular mechanisms were validated using colony formation assays, transwell migration assays, wound healing assays to assess cell migration, and osteoclastogenesis assays to evaluate osteoclast differentiation. Potential therapeutic drugs and their binding affinities were predicted using the CMap database and Kdeep. The interaction between the small-molecule drug and its target protein was confirmed by surface plasmon resonance (SPR) and drug affinity responsive target stability (DARTS) assays. Mechanistic insights and therapeutic efficacy were further validated using patient-derived organoid (PDO) cultures, drug sensitivity assays, and in vivo drug treatments. Results: Our results identified the XLOC_006941/hsa-miR-543/NPRL3 axis as a key regulatory pathway in LUADBM. We also demonstrated that GATA3-driven Th2 cell infiltration creates an immunosuppressive microenvironment that promotes metastasis. Additionally, we confirmed that the inhibitor E7449 effectively targets NPRL3, and its combination with the IL4R-blocking antibody dupilumab resulted in improved therapeutic outcomes in LUADBM. Conclusions: These findings offer new insights into the molecular mechanisms of LUADBM and highlight potential therapeutic targets, including the XLOC_006941/miR-543/NPRL3 axis and GATA3-driven Th2 cell infiltration. The dual-target therapy combining E7449 with dupilumab shows promise for improving patient outcomes in LUADBM, warranting further clinical evaluation.

BACKGROUND:The leiomyosarcoma (LMS) is the most common soft tissue sarcoma, and its molecular subtypes were identified with therapeutic sensitivity and prognosis. We aimed to develop and validate deep learning (DL) algorithms to stratify molecular subtypes and predict survival by using single hematoxylin-eosin stained whole slide images (WSIs). METHODS:The DL models were trained on the single WSIs ( n = 154, tiles = 1 579 215) from The Cancer Genome Atlas, and externally tested in a multicenter cohort from real world ( n = 80, tiles = 555 211). The primary performance metric was area under the receiver operating characteristic curve (AUROC), others included accuracy, recall, specificity, precision, and F1 score. The computation visualizations (CVs) were further performed to visualize the histomorphological features, and the effect was evaluated on assisting pathologists in subtyping. RESULTS:After five-fold cross-validation, the LMS_DL model based on DenseNet121 achieved an AUROC of 0.944 ± 0.001 in molecular subtyping, while the ResNet50-based DL algorithm achieved highest AUROC of 0.937 ± 0.024 in predicting 2-year overall survival. The LMS_DL model outperformed pathologists by over 30% accuracy in subtyping ( P < 0.001). The histomorphological features summarized by CVs enabled pathologists to obtain accuracy improvements in subtyping by 12.1% ± 4.4% ( P = 0.024) with less diagnostic time ( P = 0.025) and uncertainty ( P = 0.007). CONCLUSIONS:The LMS_DL models can be favorably applied in the molecular subtyping and survival prediction for LMSs to greatly alleviate the workload of pathologists with high accuracy and efficacy, which requires large prospective cohort for further validation.

BACKGROUND:The management of recurrent aggressive vertebral hemangiomas (AVHs) with neurological deficits poses a challenge due to their profuse vascularization and propensity for recurrence. The optimal approach to managing recurrence AVHs remains a topic of debate within the academic community. METHODS:A retrospective analysis was conducted on a cohort of patients who experienced recurrent AVH in the thoracic and lumbar spine at our institution from August 2015 to July 2022. A total of 31 patients, underwent treatment with either piecemeal intralesional spondylectomy (PIS) or modified total en bloc spondylectomy (MTES). Clinical documentation and surgical outcomes, including pre- and postoperative neurological function assessed by the American Spinal Injury Association (ASIA) score, Numeric Rating Scale (NRS), surgical duration, blood loss, recurrence rate, and complications, were retrospectively presented and analyzed. RESULTS:The study followed a cohort of 16 males and 15 females with recurrent AVHs in the thoracic or lumbar spine for a period ranging from 12 to 106 months. All patients presented with neurological deficits, with 20 patients undergoing PIS and 11 patients undergoing one-stage MTES. Both treatment modalities resulted in significant reductions in pain-NRS and ASIA scores. The MTES group experienced less intraoperative blood loss compared to the PIS group. During the follow-up period, four patients in the PIS group experienced recurrence. No serious complications or evidence of internal fixation failure were observed. CONCLUSIONS:The modified TES technique presents a comprehensive resection, less blood loss, lower incidence of recurrence, and effective tumor control for recurrent AVHs in thoracic and lumbar spine through post-only approach.

Objectives Osteosarcoma (OS) represents a prevalent primary malignant bone tumor with limited treatment options at present. The relationship between gut microbiota and OS remains ambiguous, with uncertainty surrounding whether this association is causal or influenced by bias. To investigate the potential link between gut microbiota and the development of OS, we conducted a two-sample Mendelian randomization (MR) analysis. Methods We employed a two-sample MR study design to elucidate the causal association between gut microbiota and OS. Our analysis encompassed a total of 196 bacterial features across five taxonomic levels: Phylum, Class, Order, Family, and Genus. The MR analysis incorporated the inverse-variance-weighted (IVW), weighted median, MR-Egger, weighted mode, and simple median methods. The primary analysis was conducted using the IVW method, and the MR results were validated through heterogeneity tests, sensitivity analysis, and pleiotropy analysis. Results Our findings revealed significant associations between nine distinct bacterial traits and OS using the IVW method. Specifically, we identified that genus. Odoribacter.id.952 (OR: 15.19; 95% CI: 2.08, 111.18; p = 0.007) and genus.Clostridiumsensustricto1.id.1873 (OR: 10.78; 95% CI: 1.78, 65.32; p = 0.009) were associated with a significantly increased risk of OS. Conversely, genus.LachnospiraceaeUCG001.id.11321 (OR: 0.21; 95% CI: 0.06, 0.70; p = 0.011) was found to significantly decrease the risk of OS. Conclusions Research suggests specific gut microbiota affect OS risk, highlighting their role in disease development and paving the way for new OS treatment strategies.

Beta-Parvin (PARVB) is an actin-binding protein with functionality in extracellular matrix binding. Recent studies suggest its potential as a biomarker for various cancers, given its role in governing several malignancies. Yet, its involvement and modulatory mechanisms in malignant melanoma remain under-explored.  In this research, we undertook a comprehensive pan-cancer analysis centered on PARVB. We probed its aberrant expression and prognostic implications, and assessed correlations between PARVB expression and immunocyte infiltration. This expression was subsequently corroborated using clinical samples. Both in vitro and in vivo, we discerned the functional ramifications of PARVB on melanoma. Furthermore, we scrutinized how HIF-1α/2α modulates PARVB and initiated a preliminary investigation into potential downstream pathways influenced by PARVB. Our results illuminate that elevated PARVB expression manifests across various tumors and significantly influences the prognosis of multiple cancers, emphasizing its peculiar expression and prognostic relevance in melanoma. Augmented PARVB levels were inversely proportional to immunocyte penetration in melanoma. Silencing PARVB curtailed cellular proliferation, migration, and invasion in vitro and decelerated tumor expansion in vivo. Notably, hypoxic conditions, triggering HIF-1α/2α activation, appear to elevate PARVB expression by anchoring to the hypoxia-specific responsive element within the PARVB promoter. Enhanced PARVB levels seem intertwined with the activation of cellular proliferation circuits and the damping of inflammatory trajectories. Collectively, these revelations posit PARVB as a potential prognostic indicator and therapeutic linchpin for malignant melanoma.

Chondrosarcoma (CS) is the second most common primary bone malignancy, known for its unique transcriptional landscape that renders most CS subtypes resistant to chemotherapy, including neoadjuvant chemotherapy commonly used in osteosarcoma (OS) treatment. Understanding the transcriptional landscape of CS and the mechanisms by which key genes contribute to chemotherapy resistance could be a crucial step in overcoming this challenge. To address this, we developed a single-cell transcriptional map of CS, comparing it with OS and normal cancellous bone. Our analysis revealed a specific increase in KDEL receptor 1 (KDELR1) expression in CS, which was closely associated with CS prognosis, tumor aggressiveness, and drug resistance. KDELR1 plays a key role in regulating membrane protein processing and secretion, as well as contributing to tumor extracellular matrix (ECM) formation and drug resistance. Further investigation using mass spectrometry proteomics and transcriptomics uncovered KDELR1's involvement in modulating the Hippo-YAP pathway activity in CS cells. The KDELR1-Integrin-PLCγ-YAP1 axis emerges as a critical process mediating drug resistance and malignant behavior in CS, offering novel insights and potential therapeutic targets for CS treatment.

Histone acetylation is an important epigenetic modification, modulating the development of many tumors. However, the functions of most histone acetylation-related genes (HARGs) and their prognostic values in Ewing sarcoma (EWS) remain unclear. The current study aimed to investigate the prognostic values and potential functions of HARGs in EWS. After collecting EWS patients with mRNA sequencing data from the Gene Expression Omnibus (GEO) database and a list of HARGs from previous studies, Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) regression were performed to construct a prognostic gene signature based on HARGs. Then, four HARGs (TAF4, ATF2, HDAC2 and OGA) composed a formula to calculate risk score for each patient in the training cohort. Based on median risk score, all patients were classified into low- and high-risk group, and patients with high-risk score had a poor survival outcome (p < 0.001). The 1-, 2-,3- and 5-year AUC (0.853, 0.886,0.909and 0.833, respectively) showed the good ability of this signature to predict the prognoses of EWS patients. In addition, distinct functional enrichment and immune-related pathways were also observed in two risk groups. All results were validated in an external cohort from two dataset in GEO database. Moreover, it was found that silencing HDAC2 expression in EWS cells significantly suppressed the cell viability and migration capability. In conclusion, this is the first study to detect the prognostic values of HARGs in EWS patients, further developing a good prognostic signature based on HARGs, and HDAC2 might be an oncogene in the development of EWS.

INTRODUCTION:Spinal chondrosarcoma exhibits higher invasiveness and a worse prognosis compared to chondrosarcoma in the extremities. The prognosis and therapeutic plan vary greatly among different pathological subtypes of chondrosarcoma. This study aimed to analyze the differences in clinical characteristics, molecular features, therapeutic effects, and prognostic factors among the subtypes of chondrosarcoma in the spine. METHODS:A retrospective review was conducted on 205 patients with spinal chondrosarcoma. The clinical features and immunohistochemical (IHC) markers were compared among the pathological subtypes of chondrosarcoma grade 1, grade 2, grade 3, mesenchymal chondrosarcoma (MCS), dedifferentiated chondrosarcoma (DCS), and clear cell chondrosarcoma (CCCS). Chondrosarcoma grade 1/2/3 are collectively referred to as conventional chondrosarcoma (CCS) for multivariate survival analysis. Univariate and multivariate analyses were performed to investigate independent prognostic factors for overall survival (OS) and recurrence-free survival (RFS) in patients with spinal chondrosarcoma. Furthermore, independent prognostic factors for OS and RFS were identified in CCS and MCS. RESULTS:MCS patients were younger than the other subtypes. Patients with chondrosarcoma grade 1/2 had better OS than those with chondrosarcoma grade 3, MCS and DCS, while only chondrosarcoma grade 1 patients showed better RFS than chondrosarcoma grade 2/3, MCS and DCS patients. Ki-67 index was higher in chondrosarcoma grade 3, MCS and DCS than chondrosarcoma grade 1/2. The comparison of IHC markers further highlighted the overexpression of P53/MDM2 in MCS and DCS. Gross total resection, including en-bloc and piecemeal resection, significantly improved OS and RFS for CCS patients, while only en-bloc resection significantly improved the prognosis of MCS patients. Chemotherapy appeared to be important for the OS of MCS patients. CONCLUSION:P53/MDM2 pathway was upregulated in MCS and DCS compared to chondrosarcoma grade 1/2. Radical tumor resection is crucial for the treatment of spinal chondrosarcoma, while MCS patients require further comprehensive treatments perioperatively.

Osteoclasts are over-activated as we age, which results in bone loss. Src deficiency in mice leads to severe osteopetrosis due to a functional defect in osteoclasts, indicating that Src function is essential in osteoclasts. G-protein-coupled receptors (GPCRs) are the targets for ∼35% of approved drugs but it is still unclear how GPCRs regulate Src kinase activity. Here, we reveal that GPR54 activation by its natural ligand Kisspeptin-10 (Kp-10) causes Dusp18 to dephosphorylate Src at Tyr 416. Mechanistically, Gpr54 recruits both active Src and the Dusp18 phosphatase at its proline/arginine-rich motif in its C terminus. We show that Kp-10 binding to Gpr54 leads to the up-regulation of Dusp18. Kiss1 , Gpr54 and Dusp18 knockout mice all exhibit osteoclast hyperactivation and bone loss, and Kp-10 abrogated bone loss by suppressing osteoclast activity in vivo. Therefore, Kp-10/Gpr54 is a promising therapeutic target to abrogate bone resorption by Dusp18-mediated Src dephosphorylation.

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.

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.

BACKGROUND:The spine is one of the common sites of esophageal cancer metastasis, with a worse prognosis than that of metastasis occurring in other sites. However, the exact mechanism underlying metastatic spinal esophageal cancer (MSEC) is poorly understood possibly due to the short survival time of patients. The aim of this study was to evaluate surgical outcomes and factors affecting the prognosis of patients with MSEC. METHODS:Enrolled in this retrospective study were 20 consecutive patients who received surgical treatment for MSEC in our hospital from 2013 to 2020. The impact of surgery on patient's quality of life was assessed by visual analog scale score and American Spinal Injury Association grade. Prognostic variables relative to traditional clinical parameters and inflammation and nutrition indicators were identified by univariate and multivariate analyses. RESULTS:The median survival time of patients with MSEC was 6 months, with a one-year survival rate of 20%. Pain relief was achieved in most patients, and nerve function was recovered in part of the patients after surgery. Analysis of clinical factors showed that total tumor resection was beneficial to overall survival of patients with MSEC. Laboratory indicators of erythrocyte sedimentation rate, neutrophil/lymphocyte ratio, and platelet/lymphocyte ratio were identified as independent prognostic factors for patients with MSEC. CONCLUSIONS:Timely surgical intervention can improve the quality of life of patients with MSEC. The preoperative erythrocyte sedimentation rate, neutrophil/lymphocyte ratio, and platelet/lymphocyte ratio could help predict the overall survival of patients with MSEC. These findings may help in decision-making for the treatment of patients with MSEC.