Abstract 1866P
Background
Treatment for neuroblastoma (NB) has been challenging though immunotherapy was applied. Evidence indicated that the autophagy plays an important part in NB. We aimed to construct and validate an autophagy-related genes (ARGs)-based prognostic signature and evaluate its relationship with immune microenvironment.
Methods
By Cox regression and least absolute shrinkage and selection operator regression, we identified differentially expressed ARGs between INSS stage 4 and INSS stage No-4. Next we constructed an ARGs risk signature followed by internal and external validation using K-M and ROC analysis. By dividing the NB samples into a high-risk group and a low-risk group based on the ARGs signatures' risk score, we further evaluated the relationship between risk score and clinical variables, then employed the Estimation of Stromal and Immune cells algorithm to calculate immune and stromal scores, subsequently determined the relationship between the ARGs-prognostic model and the immune microenvironment including targets CTLA4, IDO1, PD-1 and PD-L1.
Results
4 potential prognostic ARG DEmRNAs were screened out. BIRC5 and HK2 were regarded as risk factors (HR>1) while GRID2 and RNASEL were found to be protective (HR<1). We established a risk signature by the 4 ARGs and the risk score was calculated according to gene expression. The areas under curve (AUC) for 3-, 5-, 10-year survival respectively were 0.89, 0.905 and 0.926 of training cohort, 0.87, 0.9 and 0.92 of the internal validation and 0.8, 0.82 and 0.807 of the external validation. Respectively, patients<=18 months, INSS stage No-4 and MYCN not amplified had lower risk score. In addition, patients in the metastasis group had higher ATGs risk score. The degree of the stromal score (p<0.0001), immune score (p=0.0008) and estimate score (p=0.0015) were higher in the low-risk group than the high-risk group. Patients in the high-risk group exhibited a relatively lower expression of CTLA4, IDO1, PD-1, and PD-L1. Moreover, HLA-A, HLA-B and HLA-C showed a low proportion of the high-risk group.
Conclusions
We identified and independently validated an ARG gene risk signature and discovered its significant association with immune microenvironment.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Tianjin Medical University Cancer Institute & Hospital.
Funding
The National Key R&D Program of China.
Disclosure
All authors have declared no conflicts of interest.