The prognostic value of autophagy related genes with potential protective function in Ewing sarcoma

Abstract

Background Ewing sarcoma (ES) is the second most common primary malignant bone tumor mainly occurring in children, adolescents and young adults with high metastasis and mortality. Autophagy has been reported to be involved in the survival of ES, but the role remains unclear. Therefore, it’s necessary to investigate the prognostic value of autophagy related genes using bioinformatics methods. Results ATG2B, ATG10 and DAPK1 were final screened genes for a prognostic model. KM and risk score plots showed patients in high score group had better prognoses both in training and validation sets. C-indexes of the model for training and validation sets were 0.68 and 0.71, respectively. Calibration analyses indicated the model had high prediction accuracy in training and validation sets. The AUC values of ROC for 1-, 3-, 5-year prediction were 0.65, 0.73 and 0.84 in training set, 0.88, 0.73 and 0.79 in validation set, which suggested high prediction accuracy of the model. Decision curve analyses showed that patients could benefit much from the model. Differential and functional analyses suggested that autophagy and apoptosis were upregulated in high risk score group. Conclusions ATG2B, ATG10 and DAPK1 were autophagy related genes with potential protective function in ES. The prognostic model established by them exhibited excellent prediction accuracy and discriminatory capacities. They might be used as potential prognostic biomarkers and therapeutic targets in ES.

Additional prognostic value of polymorphisms within the 3′-untranslated region of programmed cell death pathway genes in early-stage breast cancer

“…ATG2B is a direct target of miR-130a, which inhibits autophagy and promotes cell death and chemosensitivity by downregulating ATG2B expression in chronic lymphocytic leukemia and gastrointestinal stromal tumor (GIST) ( 24 , 25 ). Conversely, ATG2B has been identified as a potential protective biomarker in Ewing’s sarcoma ( 26 ). In a recent study by Park et al., ATG2B was shown to inhibit cancer stemness in TNBC ( 27 ).…”

Prognostic value of GLCE and infiltrating immune cells in Ewing sarcoma

“…Most cases of ES are characterized by a chromosomal translocation that fuses a member of the FET family of proteins (encoded by FUS, EWSR1 and TAF15) with a member of the ETS transcription factor family, usually EWSR1-FLI1, and this alteration usually results in cascade reactions in cell proliferation, cell differentiation, the cell cycle, angiogenesis and apoptosis [ 2 ]. Genes or pathways downstream of the oncogenic chimera, such as VEGF, FGF, and EphA2 receptor, are associated with angiogenesis in ES [ 26 , 27 ]; miR-22, miR-30a-5p, miR-145, and miR-7a are associated with cell stemness [ 28 ]; the PKA/PPP1R1A/PP1 axis, NPY/Y5R/RhoA axis, and HDGF/ALCAM/GTPases axis are associated with the tumorigenesis and metastasis of patients [ [29] , [30] , [31] ]; and Beclin-1, ATG2B and ATG4B are associated with the autophagy of ES cells [ 12 , 32 , 33 ]. Therefore, genes involved in these pathways may affect the prognosis of ES patients, and it is of great significance to explore the prognostic value of the DEGs between normal subjects and ES patients, which may also be potential therapeutic targets for ES treatment.…”

“…With the development of bioinformatics, the genetic heterogeneity of ES tumors can be better analyzed and interpreted. Many novel biomarkers and therapeutic targets have been identified in ES by bioinformatics methods, such as NSUN7 [ 10 ] , STAG2 [ 11 ] , ATG2B [ 12 ], and WSB1 [ 13 ]. However, more biomarkers are still needed since improving the prognosis of patients with disseminated and recurrent ES is a complex problem that has not yet been well specified.…”

Prognostic value of PRR11 and immune cell infiltration in Ewing sarcoma

“…Thus far, numerous new prognostic biomarkers and therapeutic targets have been discovered, such as TrkC [7], STAG2 [8], RRM2 [9], miR-34a [10], and ATG2B [11]. However, considering the complexity of ES and the major challenges in its treatment, further information on the prognosis of this disease is required.…”