IFRD1 promotes tumor cells "low-cost" survival under glutamine starvation via inhibiting histone H1.0 nucleophagy.

Glutamine addiction represents a metabolic vulnerability of cancer cells; however, effective therapeutic targeting of the pathways involved remains to be realized. Here, we disclose the critical role of interferon-related developmental regulator 1 (IFRD1) in the adaptive survival of hepatocellular carcinoma (HCC) cells during glutamine starvation. IFRD1 is induced under glutamine starvation to inhibit autophagy by promoting the proteasomal degradation of the key autophagy regulator ATG14 in a TRIM21-dependent manner. Conversely, targeting IFRD1 in the glutamine-deprived state increases autophagy flux, triggering cancer cell exhaustive death. This effect largely results from the nucleophilic degradation of histone H1.0 and the ensuing unchecked increases in ribosome and protein biosynthesis associated with globally enhanced chromatin accessibility. Intriguingly, IFRD1 depletion in preclinical HCC models synergizes with the treatment of the glutaminase-1 selective inhibitor CB-839 to potentiate the effect of limiting glutamine. Together, our findings reveal how IFRD1 supports the adaptive survival of cancer cells under glutamine starvation, further highlighting the potential of IFRD1 as a therapeutic target in anti-cancer applications.

The diapause-like colorectal cancer cells induced by SMC4 attenuation are characterized by low proliferation and chemotherapy insensitivity.

In response to adverse environmental conditions, embryonic development may reversibly cease, a process termed diapause. Recent reports connect this phenomenon with the non-genetic responses of tumors to chemotherapy, but the mechanisms involved are poorly understood. Here, we establish a multifarious role for SMC4 in the switching of colorectal cancer cells to a diapause-like state. SMC4 attenuation promotes the expression of three investment phase glycolysis enzymes increasing lactate production while also suppressing PGAM1. Resultant high lactate levels increase ABC transporter expression via histone lactylation, rendering tumor cells insensitive to chemotherapy. SMC4 acts as co-activator of PGAM1 transcription, and the coordinate loss of SMC4 and PGAM1 affects F-actin assembly, inducing cytokinesis failure and polyploidy, thereby inhibiting cell proliferation. These insights into the mechanisms underlying non-genetic chemotherapy resistance may have significant implications for the field, advancing our understanding of aerobic glycolysis functions in tumor and potentially informing future therapeutic strategies.

CircFam190a: a critical positive regulator of osteoclast differentiation via enhancement of the AKT1/HSP90ß complex.

The identification of key regulatory factors that control osteoclastogenesis is important. Accumulating evidence indicates that circular RNAs (circRNAs) are discrete functional entities. However, the complexities of circRNA expression as well as the extent of their regulatory functions during osteoclastogenesis have yet to be revealed. Here, based on circular RNA sequencing data, we identified a circular RNA, circFam190a, as a critical regulator of osteoclast differentiation and function. During osteoclastogenesis, circFam190a is significantly upregulated. In vitro, circFam190a enhanced osteoclast formation and function. In vivo, overexpression of circFam190a induced significant bone loss, while knockdown of circFam190a prevented pathological bone loss in an ovariectomized (OVX) mouse osteoporosis model. Mechanistically, our data suggest that circFam90a enhances the binding of AKT1 and HSP90ß, promoting AKT1 stability. Altogether, our findings highlight the critical role of circFam190a as a positive regulator of osteoclastogenesis, and targeting circFam190a might be a promising therapeutic strategy for treating pathological bone loss.

The long transcript of lncRNA TMPO-AS1 promotes bone metastases of prostate cancer by regulating the CSNK2A1/DDX3X complex in Wnt/ß-catenin signaling.

The second most common male cancer is prostate cancer (PCa), which has a high tendency for bone metastasis. Long non-coding RNAs, including TMPO-AS1, play a crucial role in PCa progression. However, TMPO-AS1's function in PCa bone metastasis (BM) and its underlying molecular mechanisms are unclear. Herein, we found that the long transcript of TMPO-AS1 (TMPO-AS1L) was upregulated in PCa tissues with bone metastasis, and overexpression of TMPO-AS1L correlated with advanced clinicopathological features and reduced BM-free survival in patients with PCa. Upregulated TMPO-AS1L promoted, whereas downregulated TMPO-AS1L inhibited, the PCa cell bone metastatic capacity in vitro and in vivo. Mechanistically, TMPO-AS1L was demonstrated to act as a scaffold, that strengthened the interaction of casein kinase 2 alpha 1 (CSNK2A1) and DEAD-box helicase 3 X-linked (DDX3X), and activated the Wnt/ß-catenin signaling pathway, thus promoting BM of PCa. Moreover, upregulation of TMPO-AS1L in PCa resulted from transcription elongation modulated by general transcription factor IIF subunit 2 (GTF2F2). Collectively, our study provides critical insights into the role of TMPO-AS1L in PCa BM via Wnt/ß-catenin signaling, identifying TMPO-AS1L as a candidate marker of PCa bone metastasis prognosis and therapeutic target.

FOXA1-induced LINC00621 promotes lung adenocarcinoma progression via activating the TGF-ß signaling pathway.

BACKGROUND: Lung adenocarcinoma (LUAD) is highly malignant and associated with poor prognoses in patients worldwide. There has been widespread recognition that lncRNAs are tightly linked to LUAD tumorigenesis and development. Here, we identified that the LINC00621 level was increased in LUAD tissues and concerned with the poor prognoses in LUAD patients. METHODS: Bioinformatical analysis and RT-qPCR determined the level of LINC00621 in LUAD tissues and cell lines. The admeasurement of the proliferation, migration, and invasion abilities of LUAD cells was utilized in the CCK8 and Transwell formulas. Luciferase reporter assay was used to corroborate the downstream target genes of LINC00621. The phosphorylated SMAD3 protein was tested by Western blotting assay. The impression of LINC00621 knockdown on LUAD tumor growth and metastasis put into effect by murine models. ChIP-qPCR assay was carried out to verify the transcriptional regulation by FOXA1 on LINC00621. RESULTS: In vitro, the knockdown of LINC00621 significantly reduced the proliferative, migrating, and invasive abilities, the same was true for tumorigenesis and metastasis in vivo. MiR-34a-5p as a straight target of LINC00621 was ascertained, and LUAD patients with inferior miR-34a-5p levels had undesirable prognoses. Furthermore, TGFBR1 is an immediate and functional connection site of miR-34a-5p. Collectively, LINC00621 can sponge miR-34a-5p and upregulate TGFBR1 levels, which further sensitized TGF-ß signaling pathway. Finally, it was revealed that FOXA1 transcriptionally upregulated LINC00621. CONCLUSION: This study uncovered that FOXA1-induced LINC00621 promotes LUAD progression via the miR-34a-5p/TGFBR1/TGF-ß axis, and is one novel therapeutic target that may be used in LUAD treatment.

Histone lysine methyltransferase SMYD3 promotes oral squamous cell carcinoma tumorigenesis via H3K4me3-mediated HMGA2 transcription.

BACKGROUND: Epigenetic dysregulation is essential to the tumorigenesis of oral squamous cell carcinoma (OSCC). SET and MYND domain-containing protein 3 (SMYD3), a histone lysine methyltransferase, is implicated in gene transcription regulation and tumor development. However, the roles of SMYD3 in OSCC initiation are not fully understood. The present study investigated the biological functions and mechanisms involved in the SMYD3-mediated tumorigenesis of OSCC utilizing bioinformatic approaches and validation assays with the aim of informing the development of targeted therapies for OSCC. RESULTS: 429 chromatin regulators were screened by a machine learning approach and aberrant expression of SMYD3 was found to be closely associated with OSCC formation and poor prognosis. Data profiling of single-cell and tissue demonstrated that upregulated SMYD3 significantly correlated with aggressive clinicopathological features of OSCC. Alterations in copy number and DNA methylation patterns may contribute to SMYD3 overexpression. Functional experimental results suggested that SMYD3 enhanced cancer cell stemness and proliferation in vitro and tumor growth in vivo. SMYD3 was observed to bind to the High Mobility Group AT-Hook 2 (HMGA2) promoter and elevated tri-methylation of histone H3 lysine 4 at the corresponding site was responsible for transactivating HMGA2. SMYD3 also was positively linked to HMGA2 expression in OSCC samples. Furthermore, treatment with the SMYD3 chemical inhibitor BCI-121 exerted anti-tumor effects. CONCLUSIONS: Histone methyltransferase activity and transcription-potentiating function of SMYD3 were found to be essential for tumorigenesis and the SMYD3-HMGA2 is a potential therapeutic target in OSCC.

BHLHE22 drives the immunosuppressive bone tumor microenvironment and associated bone metastasis in prostate cancer.

BACKGROUND: The molecular characteristics of prostate cancer (PCa) cells and the immunosuppressive bone tumor microenvironment (TME) contribute to the limitations of immune checkpoint therapy (ICT). Identifying subgroups of patients with PCa for ICT remains a challenge. Herein, we report that basic helix-loop-helix family member e22 (BHLHE22) is upregulated in bone metastatic PCa and drives an immunosuppressive bone TME. METHODS: In this study, the function of BHLHE22 in PCa bone metastases was clarified. We performed immunohistochemical (IHC) staining of primary and bone metastatic PCa samples, and assessed the ability to promote bone metastasis in vivo and in vitro. Then, the role of BHLHE22 in bone TME was determined by immunofluorescence (IF), flow cytometry, and bioinformatic analyses. RNA sequencing, cytokine array, western blotting, IF, IHC, and flow cytometry were used to identify the key mediators. Subsequently, the role of BHLHE22 in gene regulation was confirmed using luciferase reporter, chromatin immunoprecipitation assay, DNA pulldown, co-immunoprecipitation, and animal experiments. Xenograft bone metastasis mouse models were used to assess whether the strategy of immunosuppressive neutrophils and monocytes neutralization by targeting protein arginine methyltransferase 5 (PRMT5)/colony stimulating factor 2 (CSF2) could improve the efficacy of ICT. Animals were randomly assigned to treatment or control groups. Moreover, we performed IHC and correlation analyses to identify whether BHLHE22 could act as a potential biomarker for ICT combination therapies in bone metastatic PCa. RESULTS: Tumorous BHLHE22 mediates the high expression of CSF2, resulting in the infiltration of immunosuppressive neutrophils and monocytes and a prolonged immunocompromised T-cell status. Mechanistically, BHLHE22 binds to the CSF2 promoter and recruits PRMT5, forming a transcriptional complex. PRMT5 epigenetically activates CSF2 expression. In a tumor-bearing mouse model, ICT resistance of Bhlhe22+ tumors could be overcome by inhibition of Csf2 and Prmt5. CONCLUSIONS: These results reveal the immunosuppressive mechanism of tumorous BHLHE22 and provide a potential ICT combination therapy for patients with BHLHE22+ PCa.

m6 A modification of lncRNA PCAT6 promotes bone metastasis in prostate cancer through IGF2BP2-mediated IGF1R mRNA stabilization.

BACKGROUND: Bone metastasis is the leading cause of tumor-related death in prostate cancer (PCa) patients. Long noncoding RNAs (lncRNAs) have been well documented to be involved in the progression of multiple cancers. Nevertheless, the role of lncRNAs in PCa bone metastasis remains largely unclear. METHODS: The expression of prostate cancer-associated transcripts was analyzed in published datasets and further verified in clinical samples and cell lines by RT-qPCR and in situ hybridization assays. Colony formation assay, MTT assay, cell cycle analysis, EdU assay, Transwell migration and invasion assays, wound healing assay, and in vivo experiments were carried out to investigate the function of prostate cancer-associated transcript 6 (PCAT6) in bone metastasis and tumor growth of PCa. Bioinformatic analysis, RNA pull-down, and RIP assays were conducted to identify the proteins binding to PCAT6 and the potential targets of PCAT6. The therapeutic potential of targeting PCAT6 by antisense oligonucleotides (ASO) was further explored in vivo. RESULTS: PCAT6 was upregulated in PCa tissues with bone metastasis and increased PCAT6 expression predicted poor prognosis in PCa patients. Functional experiments found that PCAT6 knockdown significantly inhibited PCa cell invasion, migration, and proliferation in vitro, as well as bone metastasis and tumor growth in vivo. Mechanistically, METTL3-mediated m6 A modification contributed to PCAT6 upregulation in an IGF2BP2-dependent manner. Furthermore, PCAT6 upregulated IGF1R expression by enhancing IGF1R mRNA stability through the PCAT6/IGF2BP2/IGF1R RNA-protein three-dimensional complex. Importantly, PCAT6 inhibition by ASO in vivo showed therapeutic potential against bone metastasis in PCa. Finally, the clinical correlation of METTL3, IGF2BP2, IGF1R, and PCAT6 was further demonstrated in PCa tissues and cells. CONCLUSIONS: Our study uncovers a novel molecular mechanism by which the m6 A-induced PCAT6/IGF2BP2/IGF1R axis promotes PCa bone metastasis and tumor growth, suggesting that PCAT6 may serve as a promising prognostic marker and therapeutic target against bone-metastatic PCa.

SMAD3/SP1 complex-mediated constitutive active loop between lncRNA PCAT7 and TGF-ß signaling promotes prostate cancer bone metastasis.

Bone metastasis is associated with cancer-related death in patients with prostate cancer (PCa). Long noncoding RNAs (lncRNAs) play critical roles in tumor progression of PCa. Nevertheless, the biological function of lncRNAs in PCa bone metastasis remains unclear. PCAT7 was identified as a bone metastasis-related lncRNA via analyzing TCGA dataset. Meanwhile, PCAT7 was found to be elevated in primary PCa tissues with bone metastasis and associated with bone metastasis status and poor prognosis of patients with PCa. Functionally, our results reveal that PCAT7 overexpression promotes PCa bone metastasis in vivo, as well as migration, invasion, and EMT of PCa cells in vitro; on the contrary, PCAT7 knockdown has an inverse effect. Mechanistically, PCAT7 activates TGF-ß/SMAD signaling by upregulating TGFBR1 expression via sponging miR-324-5p. In turn, TGF-ß signaling forms a positive feedback loop with PCAT7 via SMAD3/SP1 complex-induced PCAT7 upregulation. Finally, the clinical positive correlation between PCAT7 and TGFBR1 and TGF-ß signaling activity, and the negative association with miR-324-5p are further demonstrated in PCa tissues and clinical primary PCa cells. This study reveals a novel mechanism that is responsible for the constitutive activation of TGF-ß signaling in PCa bone metastasis, implying that PCAT7 can act as a potential therapeutic target against bone metastasis of PCa via disrupting the constitutive active loop between PCAT7 and TGF-ß signaling.

MAZ promotes prostate cancer bone metastasis through transcriptionally activating the KRas-dependent RalGEFs pathway.

BACKGROUND: Clinically, prostate cancer (PCa) exhibits a high avidity to metastasize to bone. Myc-associated zinc-finger protein (MAZ) is a well-documented oncogene involved in the progression and metastasis of multiple cancer types, even in PCa. However, the clinical significance and biological roles of MAZ in bone metastasis of PCa remain unclear. METHODS: MAZ expression was examined in PCa tissues with bone metastasis, PCa tissues without bone metastasis and metastatic bone tissues by real-time PCR and immunohistochemistry (IHC), respectively. Statistical analysis was performed to evaluate the clinical correlation between MAZ expression and clinicopathological features and bone metastasis-free survival in PCa patients. Biological roles of MAZ in bone metastasis of PCa were investigated both in vitro by transwell assay, and in vivo by a mouse model of left cardiac ventricle inoculation. The bioinformatics analysis, western blot, pull-down assays, chromatin immunoprecipitation (ChIP) and luciferase reporter assays were applied to demonstrate and examine the relationship between MAZ and its potential downstream signalling pathway. TaqMan copy number assay was performed to identify the underlying mechanism responsible for MAZ overexpression in PCa tissues. RESULTS: MAZ expression is elevated in PCa tissues with bone metastasis compared with that in PCa tissues without bone metastasis, and is further increased in metastatic bone tissues. High expression of MAZ positively correlates with poor overall and bone metastasis-free survival in PCa patients. Upregulating MAZ elevates, while silencing MAZ represses the invasion and migration abilities of PCa cells in vitro and bone metastasis ability in vivo. Our results further reveal that MAZ promotes bone metastasis of PCa dependent on KRas signalling, although MAZ transcriptionally upregulates KRas and HRas expression, where the Ral guanine nucleotide exchange factor (RalGEF) signaling is responsible for the different roles of KRas and HRas in mediating the pro-bone metastasis of MAZ in PCa. Finally, our results indicate that recurrent gains contribute to MAZ overexpression in a small portion of PCa tissues. CONCLUSION: These results indicate that the MAZ/Kras/ RalGEF signalling axis plays a crucial role in promoting PCa cell bone metastasis, suggesting a potential therapeutic utility of MAZ in bone metastasis of PCa.

Copy number gain of ZEB1 mediates a double-negative feedback loop with miR-33a-5p that regulates EMT and bone metastasis of prostate cancer dependent on TGF-ß signaling.

Background: The reciprocal repressive loop between ZEB1 and miRNAs has been extensively reported to play an important role in tumor progression and metastasis of various human tumor types. The aim of this study was to elucidate the role and the underlying mechanism of the double-negative feedback loop between ZEB1and miR-33a-5p in bone metastasis of prostate cancer (PCa). Methods: miR-33a-5p expression was examined in 40 bone metastatic and 165 non-bone metastatic PCa tissues by real-time PCR. Statistical analysis was performed to evaluate the clinical correlation between miR-33a-5p expression and clinicopathological characteristics, and overall and bone metastasis-free survival in PCa patients. The biological roles of miR-33a-5p in bone metastasis of PCa were investigated both by EMT and the Transwell assay in vitro, and by a mouse model of left cardiac ventricle inoculation in vivo. siRNA library, real-time PCR and chromatin immunoprecipitation (ChIP) were used to identify the underlying mechanism responsible for the decreased expression of miR-33a-5p in PCa. Bioinformatics analysis, Western blotting and luciferase reporter analysis were employed to examine the relationship between miR-33a-5p and its potential targets. Clinical correlation of miR-33a-5p with its targets was examined in human PCa tissues and primary PCa cells. Results: miR-33a-5p expression was downregulated in PCa tissues with bone metastasis and bone-derived cells, and low expression of miR-33a-5p strongly and positively correlated with advanced clinicopathological characteristics, and shorter overall and bone metastasis-free survival in PCa patients. Upregulating miR-33a-5p inhibited, while silencing miR-33a-5p promoted EMT, invasion and migration of PCa cells. Importantly, upregulating miR-33a-5p significantly repressed bone metastasis of PC-3 cells in vivo. Our results further revealed that recurrent ZEB1 upregulation induced by copy number gains transcriptionally inhibited miR-33a-5p expression, contributing to the reduced expression of miR-33a-5p in bone metastatic PCa tissues. In turn, miR-33a-5p formed a double negative feedback loop with ZEB1 in target-independent manner, which was dependent on TGF-ß signaling. Finally, the clinical negative correlations of miR-33a-5p with ZEB1 expression and TGF-ß signaling activity were demonstrated in PCa tissues and primary PCa cells. Conclusion: Our findings elucidated that copy number gains of ZEB1-triggered a TGF-ß signaling-dependent miR-33a-5p-mediated negative feedback loop was highly relevant to the bone metastasis of PCa.

Incidence and Risk Factors of Cardiac Abnormalities in Patients with Idiopathic Scoliosis.

OBJECTIVE: We sought to investigate the incidence of cardiac abnormalities in patients with idiopathic scoliosis and identify risk factors related to cardiac abnormalities. METHODS: A cohort of 531 patients with idiopathic scoliosis requiring surgical treatment in our hospital from March 2009 to August 2017 were recorded. Clinical data including medical records, radiograph, and echocardiogram were collected. All patients were divided into groups: control, congenital heart disease (CHD), and other cardiac abnormalities (OCAs). The incidence and related factors for cardiac abnormalities were analyzed. RESULTS: The age of the study cohort was 17.8 ± 7.3 years. The average Cobb angle was 57.7 ± 16.5 degrees. Cardiac abnormalities were found in 149 (28.06%) patients, including 22 (4.14%) with CHD and 127 (23.92%) with OCAs. Atrial septal defect was the most common CHD with an incidence of 1.13% (6 of 531). Mitral valve prolapse was detected in 62 (11.68%) patients, which was the most prevalent OCA. Patients with CHD or OCAs weighed less as compared with patients without cardiac abnormalities. Low height was associated with CHD in patients with idiopathic scoliosis. Six patients with severe cardiac abnormalities must undergo cardiac intervention before scoliosis surgery. CONCLUSIONS: The overall incidence of cardiac abnormalities was 28.81% in patients with idiopathic scoliosis. An echocardiogram may be helpful as a preoperative examination for patients with idiopathic scoliosis before scoliosis surgery.

Coronal deformity angular ratio may serve as a valuable parameter to predict in-brace correction in patients with adolescent idiopathic scoliosis.

BACKGROUND CONTEXT: In-brace correction (IBC) plays an important role in curve progression of patients with adolescent idiopathic scoliosis (AIS) under brace treatment. We evaluated the coronal deformity angular ratio (C-DAR) as a potential predictor of IBC. Based on our experience, we postulated that a high C-DAR may result in low IBC. This relationship had not been previously studied. PURPOSE: To evaluate the relationship of C-DAR and IBC in patients with AIS. STUDY DESIGN/SETTING: A retrospective study. PATIENT SAMPLE: A total of 119 patients with AIS treated with a Gensingen brace in our scoliosis center from July 2015 to October 2017 were included. OUTCOME MEASURES: In-brace correction. METHODS: Data were collected before and upon brace placement. Correlation analyses between study variables and IBC were performed. A linear regression model was established on the basis of C-DAR. RESULTS: At brace fitting, the average age was 12.62±1.16 (range, 10-15) years and mean major curve Cobb angle was 32.14±4.66° (range, 25-40°). Mean IBC was 59.62%±22.03% (range, 16.2-100%). IBC had significant correlation with C-DAR (r=-0.69; 95% confidence interval, -0.77 to -0.61; p<.001). IBC was not significantly correlated with age, sex, height, weight, BMI, menstrual status, or Risser sign. A simple linear regression model established that in-brace correction=115.4-10.7×C-DAR. CONCLUSIONS: C-DAR has strong negative correlation with IBC and may estimate the expected IBC. The usage of C-DAR may obviate the need for flexibility radiographs, such as supine or supine lateral bending radiographs.

Factors That Influence In-Brace Correction in Patients with Adolescent Idiopathic Scoliosis.

OBJECTIVE: To identify the factors affecting in-brace correction in patients with adolescent idiopathic scoliosis (AIS). METHODS: We performed a retrospective analysis of patients with AIS receiving Gensingen brace treatment in our scoliosis center from July 2015 to October 2017 was performed. The selection of patients was in accordance with the Scoliosis Research Society inclusion criteria for a bracing study. Some radiographic and clinical parameters, including the Cobb angle, rib-vertebra angle difference, coronal and sagittal balance, lumbar-pelvic relationship (LPR), Risser sign, curve type, age, gender, height, weight, body mass index, and menstrual status were collected. The correlation and difference analyses were performed to identify the factors influencing in-brace correction. RESULTS: A cohort of 112 patients with AIS (94 girls and 18 boys) were included in the present study. The mean in-brace correction was 59.29% ± 22.33% (range, 16.22%-100.00%). In-brace correction showed a significantly negative correlation with the major curve Cobb angle, minor curve Cobb angle, total curve Cobb angle, and LPR (P < 0.05 for all). Sagittal and coronal imbalance could reduce the curve correction (P < 0.001 and P = 0.008, respectively). The remaining parameters were not related to in-brace correction. CONCLUSIONS: In-brace correction in the present study was 59.29% ± 22.33% (range, 16.22%-100.00%). Some factors, including the Cobb angle, sagittal and coronal balance, and LPR, have an effect on in-brace correction. The results from the present study can provide some useful information for brace design and fabrication.

Increased survival of patients aged 0-29 years with osteosarcoma: A period analysis, 1984-2013.

PURPOSE: Osteosarcoma is the most common primary malignancy of bone, and typically occurs among children and adolescence. This study aims to evaluate treatment outcomes among children, adolescents and young adults with osteosarcoma over the three decades by the changes in the long-term relative survival. METHODS: Osteosarcoma incidence and relative survival data from Surveillance, Epidemiology, and End Results (SEER) registries during 1984-2013 were analyzed. The survival differences over three decades, age, sex, race, and socioeconomic status (SES) were assessed by comparing Kaplan-Meier curves. RESULTS: The overall incidence of osteosarcoma kept relatively stable with 0.4 per 100 000 in the three decades with the peak incidence occurring in the aged 10-19 group. The 10-year relative survival rate (RSR) increased from 57.7% to 61.0% in the three decades, with the greatest increase in the aged 0-9 group from 48.2% to 65.7%. The 10-year RSR improved from 54.1% to 61.5% in males, and from 62.4% to 63.0% in females, respectively, in the three decades. Furthermore, survival dramatically improved from 30% to 60% in the high-poverty group over the three decades. CONCLUSION: This study demonstrated that the overall incidence of osteosarcoma remained stable, with an improvement in survival in the three decades. The improved survival was greater in males than in females in the three decades. Furthermore, the survival significantly increased in high-poverty group, which was attributed to increasing improved health care system and patients with low finance can also have access to receiving effective and consistent treatment without distinction.

Radiologic Parameters Can Affect the Preoperative Decision Making of Three-Column Spinal Osteotomies in the Treatment of Severe and Stiff Kyphoscoliosis.

STUDY DESIGN: Retrospective analysis. OBJECTIVE: To evaluate whether radiologic parameters affect spine surgeon's osteotomy choice in patients with severe and stiff thoracic kyphoscoliosis. SUMMARY OF BACKGROUND DATA: Three-column osteotomies were developed to address severe and stiff kyphoscoliosis. Current choice on osteotomies is based on the morphology of kyphosis, global balance, and locations of the main curvature; however, quantitative basis for decision making is still lacking. METHODS: Sixty patients with severe and stiff thoracic kyphoscoliosis who underwent three-column osteotomy in the thoracic spine were classified into four groups according to the grade of osteotomy. The radiologic parameters including maximum scoliosis, maximum kyphosis, deformity angular ratio (DAR; maximum Cobb angle divided by number of vertebrae involved), apical vertebral translation, coronal balance, and sagittal balance were measured and compared. Correlation analysis between the radiologic parameters and the osteotomy grades was conducted. Perioperative and long-term complications were reviewed. RESULTS: The overall scoliosis was corrected from a mean preoperative Cobb angle of 129.1° (range, 90-174°) to 56.4° (range, 14-100°), and overall kyphosis was corrected from 124.3° (range, 64-180°) to 54.3° (range, 11-95°). As the osteotomy grades increased, the mean preoperative maximum kyphosis increased from 104.5° to 151.8° and the mean sagittal DAR (S-DAR) increased from 16.4 to 24.9. Statistically significant between-group differences were found for preoperative maximum kyphosis (P = 0.001), S-DAR (P = 0.045), and total DAR (P = 0.033). Significant correlations were observed between the preoperative maximum kyphosis and the osteotomy grade (r = 0.454, P < 0.001). The S-DAR significantly correlated with the osteotomy grade (r = 0.322, P = 0.012). CONCLUSION: The preoperative maximum kyphosis and the S-DAR may affect the surgeon's decision on the grade of osteotomies. This may enrich the theoretical basis on preoperative planning and help with patient counseling. LEVEL OF EVIDENCE: 4.