Abstract

Background: Osteosarcoma is a common malignancy of bone with inferior survival outcome. Autophagy can exert multifactorial influence on tumorigenesis and tumor progression. However, the specific function of genes related to autophagy in the prognosis of osteosarcoma patients remains unclear. Herein, we aimed to explore the association of genes related to autophagy with the survival outcome of osteosarcoma patients. Methods: The autophagy-associated genes that were related to the prognosis of osteosarcoma were optimized by LASSO Cox regression analysis. The survival of osteosarcoma patients was forecasted by multivariate Cox regression analysis. The immune infiltration status of 22 immune cell types in osteosarcoma patients with high and low risk scores was compared by using the CIBERSORT tool. Results: The risk score model constructed according to 14 autophagy-related genes (ATG4A, BAK1, BNIP3, CALCOCO2, CCL2, DAPK1, EGFR, FAS, GRID2, ITGA3, MYC, RAB33B, USP10, and WIPI1) could effectively predict the prognosis of patients with osteosarcoma. A nomogram model was established based on risk score and metastasis. Conclusion: Autophagy-related genes were identified as pivotal prognostic signatures, which could guide the clinical decision making in the treatment of osteosarcoma.

Highlights

  • Osteosarcoma is a common malignancy of bone with inferior survival outcome

  • Autophagy is a biological process mediated by certain genes, in which the aberrant organelles as well as macromolecules are digested by lysosomes, and it is involved in multiple processes such as cell metabolism, renewal of organelles and intracellular homeostasis maintenance [4, 6]

  • For the 85 osteosarcoma samples with complete survival information in the TARGET database, we used the factoextra function package in R language to perform cluster analysis based on the expression levels of 210 genes which were related to autophagy

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Summary

Introduction

Osteosarcoma is a common malignancy of bone with inferior survival outcome. Autophagy can exert multifactorial influence on tumorigenesis and tumor progression. The specific function of genes related to autophagy in the prognosis of osteosarcoma patients remains unclear. We aimed to explore the association of genes related to autophagy with the survival outcome of osteosarcoma patients. Osteosarcoma, known as osteogenic sarcoma, is considered to be the most common malignancy in bone among children and adolescents [1, 2]. The metaphyseal region is the most common location of osteosarcoma, this disease usually progresses rapidly and is prone to metastasis [3, 4]. Several studies have indicated the relationship of autophagy with the initiation and progression of various diseases, such as cancer and diseases associated with neurodegeneration and immunization [7]. Autophagy could inhibit the tumorigenesis via limiting tissue damage and Pathology & Oncology Research

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