KIF20A is associated with clinical prognosis and synergistic effect of gemcitabine combined with ferroptosis inducer in lung adenocarcinoma

Abstract

Gemcitabine (GEM), an antimetabolite that terminates DNA synthesis, is commonly used in the treatment of cancers including lung adenocarcinoma (LUAD). However, downregulation of sensitivity limits the therapeutic effect. Ferroptosis as the new form of regulated cell death has been shown to have great potential for cancer treatment with chemoresistance. Here, three genes with both ferroptosis and GEM-response-associated features were screened from RNA sequencing and public data for constructing an independent risk model. LUAD patients with different risk scores had differences in mutational landscape, gene enrichment pathways, and drug sensitivity. By Cell Counting Kit-8 assay, flow cytometry, and colony forming assay, we demonstrate that GEM and ferroptosis inducer (FIN) imidazole Ketone Erastin had a synergistic combined anti-proliferative effect on LUAD cells and knockdown of KIF20A (the core gene of our model) further enhanced cell death in vitro by inducing ferroptosis. In conclusion, we identified a link between ferroptosis and GEM response in LUAD cells and developed a robust signature that can effectively classify LUAD patients into subgroups with different overall survival. For LUAD, the combined treatment modality of GEM and FIN is potentially effective and KIF20A may be a new therapeutic target.

Bioinformatics Analysis of Programmed Cell Death in Spinal Cord Injury

“…In addition, Cdk1 can also mediate phosphorylation of Ulk1 and Atg13, thus promoting autophagy 55 . Except Cdk1, other hub genes have not been studied in SCI, but they all have the functions of regulating cell cycle, promoting cell proliferation and inhibiting apoptosis, necroptosis, pyroptosis and ferroptosis in other diseases [57][58][59][60][61][62][63][64][65][66][67] .…”

GINS2 regulates temozolomide chemosensitivity via the EGR1/ECT2 axis in gliomas

“…pLV2-CMV-ECT2-Neo plasmid (P38188), pLVX-CMV-EGR1-Neo plasmid (P237880) and corresponding vector plasmid were purchased from MiaoLing Biologicals (Wuhan, China). For the lentiviral infection assay, steps were performed as previously described [ 66 ].…”

BDH1‐mediated LRRC31 regulation dependent on histone lysine β‐hydroxybutyrylation to promote lung adenocarcinoma progression

“…Candidate genes were selected through LASSO analysis for constructing a prognostic risk model. Risk scores for each sample were computed using the following formula: risk scores = sum (expression of each candidate gene × corresponding LASSO regression coefficient) 53 . The GSE72094 dataset served as the training cohort, while TCGA–LUAD was employed as the validation cohort for analyzing the prognostic model.…”

“…CCK-8 assay, colony formation assay, tumor sphere formation assay, wound healing assay, Transwell migration, and invasion assay These methodologies have been comprehensively detailed in previous studies, and in this study, they were performed in line with established protocols. [53][54][55][56]…”