Imexon

Phosphatidylinositol binding clathrin assembly protein interacting mitotic regulator (PIMREG) plays a significant role in metaphase-to-anaphase transition in cell cycle. Its aberrant expression has been reported to be in correlation with the development of several tumors. However, its role in melanoma remains unknown. This study aimed to investigate the diagnostic and prognostic roles of PIMREG in skin cutaneous melanoma (SKCM).

The expression levels of PIMREG were analyzed in SKCM using datasets downloaded from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO). The diagnostic accuracy was assessed using the receiver operating characteristic (ROC) curve. PIMREG was correlated to the functional states of SKCM cells using CancerSEA. Additionally, a protein-protein interaction network was constructed using STRING (https://cn.string-db.org), and hub genes were identified using Cytoscape. Enrichment analysis through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) was utilized to explore the potential functions of PIMREG. The single-sample GSEA (ssGSEA) method was employed to investigate the correlation between PIMREG expression and the level of immune infiltration in SKCM. Drug sensitivity and resistance were analyzed using GSCALite and Cellminer.

The expression of PIMREG was significantly higher in SKCM tissues. Its overexpression correlated with poor survival outcome in melanoma patients. ROC analysis also revealed that PIMREG had high diagnostic potential, with area under the ROC curve (AUC) value of 0.874. Multivariate regression also identified PIMREG could serve as an independent diagnostic indicator for SKCM. Using the web tool of CancerSEA, we demonstrated that PIMREG is involved in cell cycle, DNA repair, DNA damage, epithelial-mesenchymal transition (EMT), invasion, and proliferation. Functional enrichment analysis revealed that PIMREG might be correlated with some biological processes (BPs) and important pathways related to cancer, including Wnt signaling and epidermis development.

PIMREG is a promising diagnostic and prognostic biomarker and may be regarded as a possible therapeutic target for SKCM.

The onset of drug resistance in advanced cancer patients markedly diminishes their prognosis. Recently, disulfidptosis, a novel form of cell death, has been identified, triggered by excessive disulfide formation leading to cell shrinkage and F-actin contraction. Previous studies have identified 15 essential genes (FLNA, FLNB, MYH9, TLN1, ACTB, MYL6, MYH10, CAPZB, DSTN, IQGAP1, ACTN4, PDLIM1, CD2AP, INF2, SLC7A11) associated with disulfidptosis. This study sourced pan-cancer mRNA expression data from Xena to thoroughly evaluate the molecular and clinical characteristics of disulfidptosis-related genes. Through unsupervised clustering, mRNA expression data identified the expression levels of disulfidptosis-related genes and potential clusters related to this form of cell death. Kaplan-Meier survival curves illustrated the correlation between different clusters and overall survival. The findings reveal that high expression of disulfidptosis-related genes is linked to poor survival in liver cancer. The GDSC database was utilized to analyze the relationship between disulfidptosis-related genes and the AUC of 198 drugs. The results demonstrate that 12 disulfidptosis-related genes influence sorafenib resistance, as revealed by the intersection of differential genes related to sorafenib resistance from the GSE109211 dataset. Among them, the MYH9 gene was found to play a crucial role in both. Finally, experimental evidence confirmed that MYH9 mitigates sorafenib resistance in hepatocellular carcinoma through disulfidptosis-like changes. This study identifies disulfidptosis as a promising avenue for enhancing the sensitivity of tumor cells to drugs, offering new therapeutic perspectives for future research on disulfidptosis and drug resistance in cancer patients.