50P Combination of platinum-based chemotherapy with immunotherapy in treatment of extrapulmonary neuroendocrine carcinoma: A retrospective study

Background: The spliceosome plays an important role in mRNA splicing and is aberrantly expressed in many malignancies.Herein, we study the association between SRGs, survival outcomes, and clinical features of patients with ACC.Methods: Genetic and clinical data of 79 ACC patients were obtained from TCGA, with gene expression data of 274 normal adrenal gland samples retrieved from the Genotype Tissue Expression database.GEO studies (GSE3337, GSE10927) with 47 ACC patients served as validation cohorts.Differential expression analysis was performed between ACC and normal tissues, and the resulting differentially expressed genes (DEGs) were intersected with 127 SRGs obtained from the molecular signature database.Intersecting the DEGs with SRGs identified the differentially expressed SRGs, which were analyzed via uni-and multivariate Cox models to identify survival predictors.The risk score was calculated by multiplying the expression level of each significant gene by its hazard regression coefficient and summing the values across all significant genes.Kaplan-Meier analysis and log-rank tests correlated the risk score with overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS).Time-dependent ROC curves evaluated prognostic performance at 1, 3, and 5year intervals.Pearson's Chi-squared and Wilcoxon rank sum tests correlated risk groups with clinical features.Results: Eight SRGs (SNRPG, SNRPD1, HNRNPA1, LSM4, HSPA2, ALYREF, SF3A2, and SLU7) were identified as independent predictors of survival.The median of the risk score stratified patients into High (n40) and Low (n39) risk groups.The low risk group had superior OS, PFS, and DSS (p 0.0005, p 0.0002, p0.0006) respectively.Time dependent-ROC curves showed the risk score had higher AUCs for 1-and 3-year OS prediction (AUC:0.80,0.88).The high risk group had higher TMB values (p<0.05) but no significant differences in other clinical variables.Validation cohorts provided consistent results with low-risk group (n22) showing better OS (p 0.00088).Conclusions: Our findings highlight the association between SRGs and survival outcomes in ACC, supporting the utility of a SRGs risk signature to predict survival in this disease.