Experimental evidence for NOG as a promoter of TGF-β/SMAD signaling in pancreatic cancer cells

Pancreatic adenocarcinoma (PAAD) is a common malignancy characterized by high mortality. TGF-β signaling has been implicated in tumor initiation and development. This study aimed to construct a prognostic model based on TGF-β pathway-related genes for patients with PAAD. PAAD samples and TGF-β pathway-related gene sets were obtained from public databases and the MSigDB, respectively. Prognostic genes were screened by univariate, LASSO, and stepwise regression analyses to develop a Riskscore model. Subsequently, the model’s performance was validated by timeROC package. The overall survival (OS) was analyzed based on Kaplan-Meier (K-M) curve. The mRNA expression level of the prognostic genes in PAAD cells was measured by qRT-PCR. The ESTIMATE and CIBERSORT algorithms were employed to assess immune cell infiltration. Patient response to immunotherapy was predicted by TIDE and SubMap analyses. Drug sensitivity was analyzed using the pRRophetic package. Pathway enrichment analysis was performed using the clusterProfiler package. Furthermore, genetic mutation characteristics were explored. A nomogram was constructed based on clinical features and the Riskscore. Six TGF-β pathway-related prognostic genes ( NOG , SP1 , EIF2A , PML , BCAR3 , and AMH ) were screened. Except for AMH , the other five genes were all highly expressed in PAAD cells. The established Riskscore model showed high predictive accuracy. Compared with the low-risk group, the high-risk group exhibited lower OS, a lower ImmuneScore, and a worse response to immunotherapy. High-risk patients were more sensitive to 16 drugs, including paclitaxel, dasatinib, and saracatinib. Pathways associated with tumor progression were notably activated in the high-risk group. The high-risk group exhibited higher somatic mutation rates frequencies of KRAS (97%) and TP53 (80%). A nomogram combining the Riskscore, Age, and pathologic_N stage demonstrated excellent prediction performance. The current findings may provide a novel prognostic assessment tool and several candidate drugs for PAAD.