Prognostic implications and molecular mechanisms of derived organoid-angiogenesis-related genes (DOARGs) in colorectal cancer

• Autores: Qian Xu, Mengli Dong, Ye Yuan, Qianqian Zhang
• Localización: Journal of physiology and biochemistry, ISSN-e 1877-8755, ISSN 1138-7548, Vol. 82, Nº. 1, 2026
• Idioma: inglés
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• Resumen

  • This research seeks to investigate the prognostic significance and molecular mechanisms of derived organoid-angiogenesis-related genes (DOARGs) in colorectal cancer (CRC). DOARGs associated with CRC prognosis were screened based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Machine learning techniques were employed to create and assess a signature based on DOARGs, and a nomogram was constructed. Additionally, assessments were conducted on the levels of tumor mutational burden (TMB), immune infiltration, potential chemotherapeutic agents, and immune therapy responses to assess variations between groups with varying risk levels. In vitro experiments, including quantitative reverse-transcription polymerase chain reaction (qRT-PCR), Western blot, CCK-8, and transwell assays were conducted to verify the expression and molecular mechanisms of the model genes. A total of 13 DOARGs significantly associated with prognosis were identified. Five model genes (tissue inhibitor of metalloproteinases 1 (TIMP1), matrix metalloproteinase-1 (MMP1), C-C motif chemokine ligand 24 (CCL24), melanotransferrin (MELTF), and lymphoid enhancer-binding factor 1 (LEF1)) were identified for prognostic signature establishment. This signature demonstrated robust predictive performance for CRC prognosis upon validation. Significant differences were observed in TMB, immune infiltration, potential chemotherapeutic responses, and immune therapy reactions between groups with varying risk levels. Subgroup analysis categorized tumor samples into C1 and C2 groups, with C1 exhibiting significantly lower survival rates compared to C2. qRT-PCR analysis indicated a marked upregulation in the expression of the five model genes in CRC cells, and low expression of CCL24 suppressed the biological functions of CRC cells. This study has developed a prognostic signature for CRC utilizing DOARGs. This signature offers novel targets for the prognosis and personalized treatment of CRC.