Systematic profiling of diagnostic and prognostic value of autophagy-related genes for sarcoma patients

Yuanhe Wang,Zheng Zhao,Huiqiang Hu,Yukun Du,Yingyi Sheng,Xiaojie Tang,Yongming Xi,Chuan Hu,Tongshuai Xu,Cheng Shao,Jianyi Li

doi:10.1186/s12885-020-07596-5

Abstract

BackgroundAutophagy-related genes (ARGs) have been confirmed to have an important role in tumorigenesis and tumor microenvironment formation. Nevertheless, a systematic analysis of ARGs and their clinical significance in sarcoma patients is lacking.MethodsGene expression files from The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx) were used to select differentially expressed genes (DEGs). Differentially expressed ARGs (DEARGs) were determined by matching the DEG and HADb gene sets, which were evaluated by functional enrichment analysis. Unsupervised clustering of the identified DEARGs was conducted, and associations with tumor microenvironment (TME), immune checkpoints, and immune cells were analyzed simultaneously. Two prognostic signatures, one for overall survival (OS) and one for disease-free survival (DFS), were established and validated in an independent set.ResultsIn total, 84 DEARGs and two clusters were identified. TME scores, five immune checkpoints, and several types of immune cells were found to be significantly different between two clusters. Two prognostic signatures incorporating DEARGs showed favorable discrimination and were successfully validated. Two nomograms combining signature and clinical variables were generated. The C-indexes were 0.818 and 0.747 for the OS and DFS nomograms, respectively.ConclusionThis comprehensive analyses of the ARG landscape in sarcoma showed novel ARGs related to carcinogenesis and the immune microenvironment. These findings have implications for prognosis and therapeutic responses, which reveal novel potential prognostic biomarkers, promote precision medicine, and provide potential novel targets for immunotherapy.

Highlights

Autophagy-related genes (ARGs) have been confirmed to have an important role in tumorigenesis and tumor microenvironment formation
Profiling of Differentially expressed ARGs (DEARGs) in sarcoma patients The differential analysis was performed between 911 normal samples and 259 sarcoma samples
The Gene Ontology (GO) analysis showed that DEARGs were mainly involved in “autophagy”, “vacuole”, “apoptotic signaling pathway”, “regulation of autophagy”, and “regulation of cellular response to stress” (Fig. 1d and e)

Summary

Introduction

Autophagy-related genes (ARGs) have been confirmed to have an important role in tumorigenesis and tumor microenvironment formation. A systematic analysis of ARGs and their clinical significance in sarcoma patients is lacking. With the development of diagnostic and therapeutic technology, the 5-year survival rate was higher than 70% in some sarcomas. As a whole, the improvement in the diagnosis and treatment for sarcoma is still slowed down [3, 4]. For advanced stage patients or patients with distant metastasis, the 5-year survival rate was lower than 20% [4]. Developing effective tools for early diagnosis and prognostic prediction plays a vital role in the tailor management of sarcoma patients. AJCC TNM staging system is widely used to evaluate the prognosis of tumors and guide treatment decisions. The accuracy of TNM staging is not satisfactory and the prognosis of patients with same TNM stage may be various

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Discussion

Conclusion