CYP27A1 (Cytochrome P450 Family 27 Subfamily A Member 1)

Our findings indicated that the deficiency of ALKBH5 mediated the enhanced synthesis of the cholesterol metabolite 27HC, which in turn inhibited ferroptosis in HCC cells and the cytotoxicity of CD8+ T cells, leading to Lenvatinib resistance in HCC cells. While the specific role of 27HC was strongly supported, the potential contributions of other CYP27A1-derived metabolites to this phenotype remain a possibility.

These findings elucidate a novel MFAP2-ITGB8-FAK-ERK1/2-ETS2-CYP27A1-LXRβ signaling axis, significantly activated by CAFs-derived MFAP2 in both in vitro and in vivo models, contributing to immune exhaustion and tumor progression. This axis offers significant therapeutic and prognostic potential for CRC, providing critical insights into CAF-mediated immune modulation and paving the way for targeted immunotherapeutic strategies.

These metabolites can regulate skin functions, and possibly have other biological functions after they enter the systemic circulation. These findings open previously unexpected, exciting new areas of research on the physiological role of lumisterols through their action on defined nuclear receptors.

CYP27A1 is implicated as a suppressor of LUAD brain metastasis via ferroptosis. The six-gene model facilitates risk stratification, and macrophage-driven microenvironment remodelling informs potential immunotherapy strategies, advancing LUAD precision oncology.

Although the BRCA2 variant did not contribute to the current phenotype, it has important implications for future cancer surveillance and family risk assessment. This case underscores the importance of combining classical cytogenetic and modern genomic methods to elucidate complex phenotypes, particularly in consanguineous populations, and highlights the need for the multidisciplinary management of patients with multilocus or incidental findings.

Felodipine and GSK2033 treatment eliminated the differential effects on TG concentration between wild-type and Ces1d-deficient hepatocytes. The results suggest that CES1/Ces1d activates PPARγ, LXR and SREBP1c pathways, thereby increasing TG synthesis and LD storage by augmenting fatty acid esterification.

In lung cancer, 27-HC not only enhances cancer cell proliferation but also stimulates lung adenocarcinoma cell invasion and metastasis. Therefore, targeting 27-HC represents a highly promising therapeutic strategy combatting respiratory diseases.

MIF acts as a novel therapeutic target by regulating macrophage polarization and chemotaxis. Lactate regulated MIF expression through histone lactylation. Targeting MIF holds promise for enhancing the efficacy of anti-PD-1 treatment.

This study identified six immunoregulatory genes that were significantly negatively associated with bladder cancer risk. These genes may serve not only as potential biomarkers for bladder cancer immunity but also contribute to a deeper understanding of the molecular mechanisms of bladder cancer.

The results of the present study further elucidated the molecular processes underlying PDAC and highlight the crucial importance of manganese metabolism in its development. These biomarkers may provide significant prognostic insights and facilitate the advancement of targeted therapeutic strategies for PDAC.

We developed an HLRGs-based prognostic model that predicts overall survival and guides treatment strategies, contributing to precision therapy in PC.

Fibroblasts and B lineage cells may significantly contribute to the reduced endometrial receptivity observed in endometriosis. These findings provide new insights into the diagnostic and pathogenic roles of LMRGs in endometriosis and highlight their implications for infertility and pregnancy complications related to endometriosis.