Search

InstructionColorectal cancer (CRC) poses a challenge to public health and is characterized by a high incidence rate. This study explored the relationship between ferroptosis and fatty acid metabolism in the tumor microenvironment (TME) of patients with CRC to identify how these interactions impact the prognosis and effectiveness of immunotherapy, focusing on patient outcomes and the potential for predicting treatment response.MethodsUsing datasets from multiple cohorts, including The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), we conducted an in-depth multi-omics study to uncover the relationship between ferroptosis regulators and fatty acid metabolism in CRC. Through unsupervised clustering, we discovered unique patterns that link ferroptosis and fatty acid metabolism, and further investigated them in the context of immune cell infiltration and pathway analysis. We developed the FeFAMscore, a prognostic model created using a combination of machine learning algorithms, and assessed its predictive power for patient outcomes and responsiveness to treatment. The FeFAMscore signature expression level was confirmed using RT-PCR, and ACAA2 progression in cancer was further verified.ResultsThis study revealed significant correlations between ferroptosis regulators and fatty acid metabolism-related genes with respect to tumor progression. Three distinct patient clusters with varied prognoses and immune cell infiltration were identified. The FeFAMscore demonstrated superior prognostic accuracy over existing models, with a C-index of 0.689 in the training cohort and values ranging from 0.648 to 0.720 in four independent validation cohorts. It also responses to immunotherapy and chemotherapy, indicating a sensitive response of special therapies (e.g., anti-PD-1, anti-CTLA4, osimertinib) in high FeFAMscore patients.ConclusionFerroptosis regulators and fatty acid metabolism-related genes not only enhance immune activation, but also contribute to immune escape. Thus, the FeFAMscore, a novel prognostic tool, is promising for predicting both the prognosis and efficacy of immunotherapeutic strategies in patients with CRC.

Primary epithelioid trophoblastic tumor (ETT) of the lung is exceedingly rare. Only about three cases have been reported in Pubmed and worldwide literature. We presented a case of multiple primary ETT of the lung occurring in a 33-year-old Chinese female patient. Comprehensive physical examinations revealed no evidence of a primary lesion on the uterus or cervix uteri. Microscopic examination of the tumor demonstrated ETT of the lung, which was confirmed by immunohistochemical staining and declining level of beta-human choriogonadotropin (β-HCG) after the operation. Our case revealed that the ETT can occur in the lung and should be considered when a female had a tumor of lung with increasing β-HCG.

MYT1L gene has been associated with various brain diseases as it affects many neuronal and biological processes of nerve cells. However, the role of MYT1L in glioma cell migration and invasion and its mechanism of action are still unclear. In this study, MYT1L was successfully silenced in U87 and A172 cells, and overexpressed in U251 cells using lentiviral vectors. The expression levels of MYT1L in glioma cells were assessed by real-time PCR and Western blot analysis. The effect of MYT1L on migration and invasion was examined by a Transwell assay. We found that MYT1L enhanced cell migration and invasion whereas knockdown of MYT1L suppressed migration and invasion in glioma cells. We also demonstrated that MYT1L activated the Notch signaling pathway, and that treatment with the Notch inhibitor DAPT inhibited the migration and invasion of glioma cells. These results suggest that MYT1L may be considered a useful and potential target in the treatment of glioma. [ABSTRACT FROM AUTHOR]

Background: Ferroptosis is associated with alcoholic hepatitis (AH); however, the underlying mechanisms remain unclear., Methods: Changes in iron content and oxidative stress in AH patients and in vivo and in vitro models were analyzed. Iron homeostasis pathways in the livers of patients with AH were investigated using RNA sequencing. AH-associated ferroptosis-related genes (FRGs) were identified using weighted gene co-expression network analysis. Hub genes were identified using machine learning methods, and their diagnostic potential for AH was assessed. The correlation between FRGs and the immune microenvironment was analyzed, and the underlying regulatory mechanism was explored. FRG expression was validated in clinical samples and in vitro and in vivo models. The role of FRGs in AH-related ferroptosis was explored through gene-silencing experiments., Results: Significant iron deposits and oxidative stress were detected in clinical samples and in vivo and in vitro AH models. Bioinformatics identified GCLC, NQO1, and ULK1 as key FRGs linked to the immune microenvironment and AH-related pathogenic genes. A nomogram based on these FRGs accurately assessed AH risk, as validated using the calibration curve. A regulatory network involving 154 miRNAs and 136 transcription factors was mapped for FRGs. In AH patients, NQO1 was upregulated in the liver, whereas GCLC and ULK1 were downregulated. Silencing GCLC and ULK1 reduced cell viability and increased oxidative stress and ferroptosis, whereas silencing NQO1 had the opposite effect., Conclusions: Therefore, GCLC, NQO1, and ULK1 are key AH-related FRGs, potentially serving as targets for diagnosing and treating AH., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2025. Published by Elsevier Inc.)