Comprehensive analysis of prognostic tumor microenvironment-related genes in osteosarcoma patients
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RESEARCH ARTICLE
Open Access
Comprehensive analysis of prognostic tumor microenvironment-related genes in osteosarcoma patients Chuan Hu1, Chuan Liu2, Shaoqi Tian1, Yuanhe Wang1, Rui Shen1, Huili Rao3, Jianyi Li1, Xu Yang1, Bo Chen4 and Lin Ye4*
Abstract Background: Tumor microenvironment (TME) plays an important role in malignant tumors. Our study aimed to investigate the effect of the TME and related genes in osteosarcoma patients. Methods: Gene expression profiles and clinical data of osteosarcoma patients were downloaded from the TARGET dataset. ESTIMATE algorithm was used to quantify the immune score. Then, the association between immune score and prognosis was studied. Afterward, a differential analysis was performed based on the high- and low-immune scores to determine TME-related genes. Additionally, Cox analyses were performed to construct two prognostic signatures for overall survival (OS) and disease-free survival (DFS), respectively. Two datasets obtained from the GEO database were used to validate signatures. Results: Eighty-five patients were included in our research. The survival analysis indicated that patients with higher immune score have a favorable OS and DFS. Moreover, 769 genes were determined as TME-related genes. The unsupervised clustering analysis revealed two clusters were significantly related to immune score and T cells CD4 memory fraction. In addition, two signatures were generated based on three and two TME-related genes, respectively. Both two signatures can significantly divide patients into low- and high-risk groups and were validated in two GEO datasets. Afterward, the risk score and metastatic status were identified as independent prognostic factors for both OS and DFS and two nomograms were generated. The C-indexes of OS nomogram and DFS nomogram were 0.791 and 0.711, respectively. Conclusion: TME was associated with the prognosis of osteosarcoma patients. Prognostic models based on TMErelated genes can effectively predict OS and DFS of osteosarcoma patients. Keywords: Tumor microenvironment, Osteosarcoma, Prognosis, Immune features, Nomogram
Background Osteosarcoma is the most common bone tumor, especially in children and adolescents [1]. It was reported that approximately 60% of patients are between 10 and 20 years old and osteosarcoma is considered as the second leading cause of death in this age group [2]. Currently, surgery and * Correspondence: [email protected] 4 Wenzhou Medical University, Wenzhou, China Full list of author information is available at the end of the article
chemotherapy are still major treatments for osteosarcoma patients, and these therapies are constantly improving in recent years. However, due to the susceptibility of local aggressiveness and lung metastasis in osteosarcoma patients, the prognosis of osteosarcoma remains unfavorable [3]. Previous studies indicated that the 5-years survival rates were 27.4 and 70% in metastatic and non-metastatic patients, respectively [4]. Therefore, it is necessary to
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