Characterization of TGFβ-Associated Molecular Features and Drug Responses in Gastrointestinal Adenocarcinoma

Abstract

\n Background: Gastrointestinal adenocarcinoma (GIAD) has caused a serious disease burden globally. Targeted therapy for the transforming growth factor beta (TGF-β) signaling pathway is becoming a reality. However, the molecular characterization of TGF-β in GIAD requires further exploration.Results: The TGF-β\xad\xadhigh group had a worse prognosis in overall GIAD patients, and had a worse prognosis trend in gastric cancer and colon cancer specifically. Signatures (including mRNA and proteins) of the TGF-β\xad\xadhigh group is highly correlated with EMT. According to miRNA analysis, miR-215-3p, miR-378a-5p, and miR-194-3p may block the effect of TGF-β. Further genomic analysis showed that TGF-β\xad\xadlow group had more genomic changes in gastric cancer, such as TP53 mutation, EGFR amplification, and SMAD4 deletion. And drug response dataset revealed sensitive drugs or drug resistant drugs corresponding to TGF-β associated mRNAs. Finally, the DNN model showed an excellent predictive effect in predicting TGF-β status in different GIAD datasets.Conclusions: Our study provided a comprehensive analysis of the molecular characteristics associated with TGF-β and provides possible therapeutic targets in GIAD.