Background Chordoma is a bone tumor that tends to occur in middle-aged and elderly people. It grows relatively slowly but is aggressive. The prognosis of middle-aged and elderly patients with chordoma is quite different from that of young patients with chordoma. Objectives The purpose of the research was to construct a nomogram to predict the Individualized prognosis of middle-aged and elderly (age greater than or equal to 40 years) patients with chordoma. Methods In this study, we screened 658 patients diagnosed with chordoma from 1983 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database. We determined the independently prognostic factors that affect the survival of patients by univariate and multivariate Cox proportional hazards model. Based on the independent prognostic factors, we constructed a nomogram to predict the overall survival (OS) rates of middle-aged and elderly patients with chordoma at 3 and 5 years. The validation of this nomogram was completed by evaluating the calibration curve and the C-index. Results We screened a total of 658 patients and divided them into two cohort. Training cohort had 462 samples and validation cohort had 196 samples. The multivariate Cox proportional hazards model of the training group showed an association of age, tumor size, histology, primary site, surgery, and extent of disease with OS rates. Based on these results, we constructed the corresponding nomogram. The calibration curve and C-index showed the satisfactory ability of the nomogram in terms of predictive ability. Conclusion Nomogram can be an effective prognostic tool to assess the prognosis of middle-aged and elderly patients with chordoma and can help clinicians in medical decision-making and enable patients to receive more accurate and reasonable treatment.
BackgroundThe incidence of chondrosarcoma is increasing every year, and the treatment and prognosis of patients with high-grade chondrosarcoma are becoming more and more important. Nomogram is a tool that can quickly and easily predict the overall survival of tumor patients. Therefore, the development and validation of a nomogram to predict overall survival in patients with high-grade chondrosarcoma was desired.MethodsWe retrospectively collected 396 patients with high-grade chondrosarcoma from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015. Randomly divided into model and validation groups, the best cut-off values for age and tumor size grouping were derived by using X-tile software. Then, independent prognostic factors for high-grade chondrosarcoma were derived by SPSS.26 univariate and multivariate Cox analyses analysis in the model group, and the model was evaluated by using R software, using C-indix and ROC curves, and finally these independent prognostic factors were included in Nomogram.Results396 patients were randomly assigned to the modelling group (n = 280) or the validation group (n = 116). Age, tissue-type, tumor size, AJCC stage, regional expansion and surgery were identified as independent prognostic factors (p < 0.05) which further combined to construct a nomogram. The C-index of internal validation for overall survival(OS) was 0.757, while the C-index of external validation for overall survival(OS) was 0.832. Both internal and external calibration curves show a good agreement between nomogram prediction and actual survival.ConclusionIn this study, we established age, tumour size, AJCC stage, tissue type, surgery and tumor extension as independent prognostic factors for high-grade chondrosarcoma and constructed a nomogram to predict 3- and 5-year survival rates for high-grade chondrosarcoma.
Extracellular matrix (ECM) production and nucleus pulposus (NP) cell migration increase under periodic mechanical stress (PMS), but the underpinning regulatory mechanism remains unclear. This work aimed to examine the regulatory effects of cytoskeleton-lipid raft-integrin α1 signaling in NP cells exposed to PMS. Briefly, In NP cells, cytoskeleton rearrangement, lipid raft aggregation and integrin α1 expression in the stress and control groups were assessed by immunofluorescent staining and immunoblot. In addition, cell migration and ECM gene expression were detected by a scratch test and quantitative reverse transcription polymerase chain reaction (qRT‑PCR), respectively. As a result, PMS up-regulated ECM gene expression and enhanced NP cell migration (both P < 0.05), accompanied by increased integrin α1, lipid raft, caveolin-3, F-actin and β-tubulin amounts. Pretreatment with the lipid raft inhibitor methyl-β-cyclodextrin (MβCD) or small interfering RNA (siRNA) targeting caveolin-3 resulted in decreased ECM mRNA synthesis and cell migration induced by PMS (both P < 0.05); meanwhile, integrin α1 expression was also reduced. F-actin and β-tubulin inhibition by cytochalasin D and colchicine, respectively, not only reduced ECM mRNA synthesis and cell migration (both P < 0.05), but also disrupted lipid raft and caveolin-3 amount increases induced by PMS in NP cells. In conclusion, PMS promotes ECM mRNA up-regulation and cell migration through the cytoskeleton-lipid raft-integrin α1 signaling pathway, inhibiting cytoskeleton and lipid rafts could block the cellular effects.