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Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma
Published on: March 3, 2023
Exploratory Transcriptomic, Genomic, Pharmacogenomic, and Cellular Evaluation of FKBP4 in Lung Adenocarcinoma
Fangyu Wang1,2, Pengfei Lyu3, Weimin Chen1,4
1Key Laboratory of Tropical Translational Medicine of the Ministry of Education, School of Basic Medical Sciences, Hainan Medical University, Haikou 571199, China.
Abstract:
FK506-binding protein 4 (FKBP4), also known as FKBP52, is an HSP90 co-chaperone associated with poor outcomes in lung adenocarcinoma (LUAD). We evaluated FKBP4 using TCGA-LUAD, cBioPortal, CellMiner, and H1299 cell data. Among 535 primary tumors, the 20 displayed FKBP4 correlations from each of the HALLMARK_APOPTOSIS and HALLMARK_PEROXISOME sets remained significant after set-wise Bonferroni correction. cBioPortal identified two FKBP4 coding alterations among 511 tumors (0.39%), without a recurrent hotspot. No CellMiner association remained significant after Benjamini-Hochberg correction across 263 activity profiles. Three siRNAs reduced FKBP4 transcript abundance in an archived qPCR screen, although independent transfections could not be confirmed. Only si-FKBP4-3 was assessed by CCK-8, and FKBP4 protein depletion was not confirmed during the assay window. In one archived experiment, mean OD450 values were higher at 48 and 72 h across five technical wells. Because CCK-8 reflects WST-8 reduction, this observation does not establish proliferation, survival, or another defined phenotype. The study therefore identifies tumor-level co-expression associations and a preliminary cellular observation requiring independent and orthogonal validation.
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