BackgroundGastrointestinal adenocarcinoma (GIAD) has caused a serious disease burden globally. Targeted therapy for the transforming growth factor beta (TGF-beta) signaling pathway is becoming a reality. However, the molecular characterization of TGF-beta associated signatures in GIAD requires further exploration.MethodsMulti-omics data were collected from TCGA and GEO database. A pivotal unsupervised clustering for TGF-beta level was performed by distinguish status of TGF-beta associated genes. We analyzed differential mRNAs, miRNAs, proteins gene mutations and copy number variations in both clusters for comparison. Enrichment of pathways and gene sets were identified in each type of GIAD. Then we performed differential mRNA related drug response by collecting data from GDSC. At last, a summarized deep neural network for TGF-beta status and GIADs was constracted.ResultsThe TGF-beta (high) 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-beta (high) 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-beta. Further genomic analysis showed that TGF-beta (low) group had more genomic changes in gastric cancer, such as TP53 mutation, EGFR amplification, and SMAD4 deletion. And drug response dataset revealed tumor-sensitive or tumor-resistant drugs corresponding to TGF-beta associated mRNAs. Finally, the DNN model showed an excellent predictive effect in predicting TGF-beta status in different GIAD datasets.ConclusionsWe provide molecular signatures associated with different levels of TGF-beta to deepen the understanding of the role of TGF-beta in GIAD and provide potential drug possibilities for therapeutic targets in different levels of TGF-beta in GIAD.
基金：
State Key Project on Infection Disease of China [2018ZX10723204-003]; Chinese Ministry of Public Health for Key Clinical Project [[2010] 493-51]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81502530, 81874189]
第一作者单位：[1]Huazhong Univ Sci & Technol, Tongji Hosp, Hubei Prov Clin Med Res Ctr Hepat Surg, Hepat Surg Ctr,Tongji Med Coll, 1095 Jiefang Ave, Wuhan 430030, Peoples R China[2]Hubei Prov Clin Med Res Ctr Hepat Surg, Wuhan 430030, Hubei, Peoples R China[3]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Hubei Key Lab Hepatopancreatobiliary Dis, Wuhan 430030, Hubei, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Huazhong Univ Sci & Technol, Tongji Hosp, Hubei Prov Clin Med Res Ctr Hepat Surg, Hepat Surg Ctr,Tongji Med Coll, 1095 Jiefang Ave, Wuhan 430030, Peoples R China[2]Hubei Prov Clin Med Res Ctr Hepat Surg, Wuhan 430030, Hubei, Peoples R China[3]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Hubei Key Lab Hepatopancreatobiliary Dis, Wuhan 430030, Hubei, Peoples R China
推荐引用方式(GB/T 7714)：
zhang qiaofeng,liu furong,qin lu,et al.Characterization of TGF beta-associated molecular features and drug responses in gastrointestinal adenocarcinoma[J].BMC GASTROENTEROLOGY.2021,21(1):doi:10.1186/s12876-021-01869-4.
APA：
zhang,qiaofeng,liu,furong,qin,lu,liao,zhibin,song,jia...&zhang,bixiang.(2021).Characterization of TGF beta-associated molecular features and drug responses in gastrointestinal adenocarcinoma.BMC GASTROENTEROLOGY,21,(1)
MLA：
zhang,qiaofeng,et al."Characterization of TGF beta-associated molecular features and drug responses in gastrointestinal adenocarcinoma".BMC GASTROENTEROLOGY 21..1(2021)
