PMID- 33591944 OWN - NLM STAT- MEDLINE DCOM- 20210723 LR - 20210723 IS - 1945-4589 (Electronic) IS - 1945-4589 (Linking) VI - 13 IP - 4 DP - 2021 Feb 11 TI - Identification of novel candidate biomarkers for pancreatic adenocarcinoma based on TCGA cohort. PG - 5698-5717 LID - 10.18632/aging.202494 [doi] AB - Pancreatic adenocarcinoma (PAAD) is the most serious solid tumor type throughout the world. The present study aimed to identify novel biomarkers and potential efficacious small drugs in PAAD using integrated bioinformatics analyses. A total of 4777 differentially expressed genes (DEGs) were filtered, 2536 upregulated DEGs and 2241 downregulated DEGs. Weighted gene co-expression network analysis was then used and identified 12 modules, of which, blue module with the most significant enrichment result was selected. KEGG and GO enrichment analyses showed that all DEGs of blue module were enriched in EMT and PI3K/Akt pathway. Three hub genes (ITGB1, ITGB5, and OSMR) were determined as key genes with higher expression levels, significant prognostic value and excellent diagnostic efficiency for PAAD. Additionally, some small molecule drugs that possess the potential to treat PAAD were screened out, including thapsigargin (TG). Functional in vitro experiments revealed that TG repressed cell viability via inactivating the PI3K/Akt pathway in PAAD cells. Totally, our findings identified three key genes implicated in PAAD and screened out several potential small drugs to treat PAAD. FAU - Jie, Yang AU - Jie Y AD - Department of Pharmacy, Shandong Provincial Hospital, Jinan 250022, Shandong, P.R. China. FAU - Peng, Wang AU - Peng W AD - Department of Pharmacy, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, Shandong, P.R. China. FAU - Li, Yuan-Yuan AU - Li YY AD - Department of Pharmacy, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, Shandong, P.R. China. LA - eng PT - Journal Article PT - Validation Study DEP - 20210211 PL - United States TA - Aging (Albany NY) JT - Aging JID - 101508617 RN - 0 (Biomarkers, Tumor) RN - 0 (ITGB5 protein, human) RN - 0 (Integrin beta Chains) RN - 0 (Integrin beta1) RN - 0 (Itgb1 protein, human) RN - 0 (MIRN16 microRNA, human) RN - 0 (MicroRNAs) RN - 67526-95-8 (Thapsigargin) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Adenocarcinoma/drug therapy/*metabolism MH - Biomarkers, Tumor/*metabolism MH - Case-Control Studies MH - Cell Line, Tumor MH - Drug Screening Assays, Antitumor MH - Gene Regulatory Networks MH - Humans MH - Integrin beta Chains/metabolism MH - Integrin beta1/metabolism MH - MicroRNAs/metabolism MH - Pancreatic Neoplasms/drug therapy/*metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - Thapsigargin/pharmacology/therapeutic use PMC - PMC7950294 OTO - NOTNLM OT - biomarker OT - connectivity map (CMap) OT - pancreatic adenocarcinoma (PAAD) OT - small molecule drug OT - weighted co-expression network analysis (WGCNA) COIS- CONFLICTS OF INTEREST: The authors declare that they have no conflicts of interest. EDAT- 2021/02/17 06:00 MHDA- 2021/07/24 06:00 PMCR- 2021/02/28 CRDT- 2021/02/16 17:10 PHST- 2020/07/02 00:00 [received] PHST- 2020/12/18 00:00 [accepted] PHST- 2021/02/17 06:00 [pubmed] PHST- 2021/07/24 06:00 [medline] PHST- 2021/02/16 17:10 [entrez] PHST- 2021/02/28 00:00 [pmc-release] AID - 202494 [pii] AID - 10.18632/aging.202494 [doi] PST - ppublish SO - Aging (Albany NY). 2021 Feb 11;13(4):5698-5717. doi: 10.18632/aging.202494. Epub 2021 Feb 11.