The crosstalk role of CDKN2A between tumor progression and cuproptosis resistance in colorectal cancer.

BACKGROUND: Cuproptosis is a type of cell death characterized by excessive copper-lipid reactions in the tricarboxylic acid cycle, resulting in protein toxicity stress and cell death. Although known as a cuproptosis inhibitor through CRISPR-Cas9 screening, the role of cyclin-dependent kinase inhibitor 2A (CDKN2A) in cuproptosis resistance and its connection to tumor development remains unclear. METHODS: In this study, we combined single-cell sequencing, spatial transcriptomics, pathological image analysis, TCGA multi-omics analysis and in vitro experimental validation to comprehensively investigate CDKN2A distribution, expression, epigenetic modification, regulation and genomic features in colorectal cancer cells. We further explored the associations between CDKN2A and cellular pathway, immune infiltration and spatial signal communication. RESULTS: Our findings showed an increasing trend in cuproptosis in the trajectory of tumor progression, accompanied by an upward trend of CDKN2A. CDKN2A underwent transcriptional activation by MEF2D and via the SNHG7/miR-133b axis, upregulating glycolysis, copper metabolism and copper ion efflux. CDKN2A likely drives epithelial-mesenchymal transition (EMT) and progression by activating Wnt signaling. CDKN2A is associated with high genomic instability and sensitivity to radiation and chemotherapy. Tumor regions expressing CDKN2A exhibit distinctive SPP1+ tumor-associated macrophage (TAM) infiltration and MMP7 enrichment, along with unique signaling crosstalk with adjacent areas. CONCLUSIONS: CDKN2A mediates cuproptosis resistance through regulating glycolysis and copper homeostasis, accompanied by a malignant phenotype and pro-tumor niche. Radiation and chemotherapy are expected to potentially serve as therapeutic approaches for cuproptosis-resistant colorectal cancer with high CDKN2A expression.

Internal fixation of humeral shaft fractures using minimally invasive plating: comparative study of two implants.

PURPOSE: We compared the results of two types of implants, dynamic compression plates (DCPs) and locking compression plates (LCPs), applied to correct mid-distal third humeral shaft fractures using minimally invasive plating osteosynthesis (MIPO). METHODS: Data of 43 patients with mid-distal third humeral shaft fractures treated using MIPO were retrospectively analyzed. Patients were divided into two groups according to the implants applied: group A (n = 26), those whose fractures were fixed with 4.5-mm DCP, and group B (n = 17) fixed with 4.5-mm LCP or metaphyseal LCP. The outcomes of the two groups in terms of operative time, time of fracture union, occurrence of early and late postoperative complications, University of California-Los Angeles (UCLA) End-Result score and the Mayo Elbow Performance Index (MEPI) were compared. RESULTS: The mean operative time was 107.8 ± 33.1 min in group A and 91.2 ± 40.4 min in group B (p > 0.05). The mean time of fracture union was 16.77 ± 6.01 weeks in group A and 14.59 ± 5.73 weeks in group B (p > 0.05). Seven (26.9 %) patients had postoperative complications in group A and 3 (17.6 %) in group B (p > 0.05). The mean UCLA End-Result score in group A was 34.31 ± 1.26 points and 33.12 ± 2.76 points in group B (p > 0.05). The mean MEPI was 100.00 ± 0.00 points in group A and 97.35 ± 7.52 points in group B (p > 0.05). CONCLUSIONS: In surgical stabilization of mid-distal humeral shaft fractures using MIPO, application of DCP or LCP resulted in good outcomes, there were no significant differences between the outcomes of these two types of implant.