A novel risk score model based on eight genes and a nomogram for predicting overall survival of patients with osteosarcoma

BMC Cancer. 2020 May 24;20(1):456. doi: 10.1186/s12885-020-06741-4.

Abstract

Background: This study aims to identify a predictive model to predict survival outcomes of osteosarcoma (OS) patients.

Methods: A RNA sequencing dataset (the training set) and a microarray dataset (the validation set) were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, respectively. Differentially expressed genes (DEGs) between metastatic and non-metastatic OS samples were identified in training set. Prognosis-related DEGs were screened and optimized by support vector machine (SVM) recursive feature elimination. A SVM classifier was built to classify metastatic and non-metastatic OS samples. Independent prognosic genes were extracted by multivariate regression analysis to build a risk score model followed by performance evaluation in two datasets by Kaplan-Meier (KM) analysis. Independent clinical prognostic indicators were identified followed by nomogram analysis. Finally, functional analyses of survival-related genes were conducted.

Result: Totally, 345 DEGs and 45 prognosis-related genes were screened. A SVM classifier could distinguish metastatic and non-metastatic OS samples. An eight-gene signature was an independent prognostic marker and used for constructing a risk score model. The risk score model could separate OS samples into high and low risk groups in two datasets (training set: log-rank p < 0.01, C-index = 0.805; validation set: log-rank p < 0.01, C-index = 0.797). Tumor metastasis and RS model status were independent prognostic factors and nomogram model exhibited accurate survival prediction for OS. Additionally, functional analyses of survival-related genes indicated they were closely associated with immune responses and cytokine-cytokine receptor interaction pathway.

Conclusion: An eight-gene predictive model and nomogram were developed to predict OS prognosis.

Keywords: Differentially expressed genes; Osteosarcoma; Prognosis; Risk score; Support vector machine.

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Bone Neoplasms / genetics
  • Bone Neoplasms / mortality*
  • Bone Neoplasms / pathology
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling
  • Gene Regulatory Networks*
  • Humans
  • Male
  • Middle Aged
  • Nomograms*
  • Osteosarcoma / genetics
  • Osteosarcoma / mortality*
  • Osteosarcoma / pathology
  • Prognosis
  • Risk Factors
  • Survival Rate

Substances

  • Biomarkers, Tumor