Translational cancer research · 2026
Establishing the role of the neurotransmitter receptor-related gene GABRD in the diagnosis, prognosis and immune infiltrates of colorectal cancer by bioinformatics analysis and experimental validation.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Wei Leiyan, Zhu Wu, Guo Zhiqin, Zhang Hong, Yuan Linna, Zhang Lin, Sun Bohao, Hu Shaoqing, Zhang Jing, Wu Wanxin, Chen Xiangyi
Аннотация
BACKGROUND: Colorectal cancer (CRC) remains a significant global health challenge, marked by high incidence and mortality rates, as well as ongoing limitations in current diagnostic and therapeutic strategies. Accurate prognostic evaluation and the customization of treatment to meet the individual requirements of patients are of paramount importance. gamma-aminobutyric acid type A receptor subunit delta (GABRD) plays a role in the progression of a number of different cancers, such as glioma, breast cancer, and stomach cancer. However, its function in CRC was rarely reported. In this study, we aimed to evaluate the diagnostic, prognostic and immune infiltration value of GABRD in CRC.
METHODS: Transcriptomic data and clinical records of CRC patients were retrieved from The Cancer Genome Atlas (TCGA). A prognostic signature based on neurotransmitter receptor-associated genes (NRGs) was developed using the least absolute shrinkage and selection operator (LASSO) Cox regression model. Functional enrichment analyses were performed. Immune cell infiltration was assessed via single-sample Gene Set Enrichment Analysis (ssGSEA). The correlation between GABRD expression and clinicopathological characteristics was analyzed, and prognostic significance was evaluated using univariate and multivariate Cox regression models, supplemented by Kaplan-Meier survival analysis. Immunohistochemical (IHC) validation of GABRD protein expression was performed on 115 CRC tissue samples. In vitro validation was conducted using reverse transcription quantitative polymerase chain reaction (RT-qPCR), Western blotting, and functional assays in CRC cell lines.
RESULTS: GABRD was significantly overexpressed in CRC tissues, with elevated levels correlating with advanced disease stages and poorer survival outcomes. Further analysis revealed that GABRD contributes to the establishment of an immunosuppressive tumor microenvironment. Functional assays highlighted GABRD's involvement in key signaling pathways, including Hedgehog, Wnt/β-catenin, and TGF-β, which are pivotal in CRC progression. Knockdown of GABRD significantly inhibited CRC cell proliferation and migration. Molecular docking simulations suggested promising drug repurposing avenues, particularly with afatinib and crizotinib, for GABRD inhibition.
CONCLUSIONS: GABRD gene may serve as a novel biomarker in the diagnosis, prognosis and immune infiltrates of CRC patients.
METHODS: Transcriptomic data and clinical records of CRC patients were retrieved from The Cancer Genome Atlas (TCGA). A prognostic signature based on neurotransmitter receptor-associated genes (NRGs) was developed using the least absolute shrinkage and selection operator (LASSO) Cox regression model. Functional enrichment analyses were performed. Immune cell infiltration was assessed via single-sample Gene Set Enrichment Analysis (ssGSEA). The correlation between GABRD expression and clinicopathological characteristics was analyzed, and prognostic significance was evaluated using univariate and multivariate Cox regression models, supplemented by Kaplan-Meier survival analysis. Immunohistochemical (IHC) validation of GABRD protein expression was performed on 115 CRC tissue samples. In vitro validation was conducted using reverse transcription quantitative polymerase chain reaction (RT-qPCR), Western blotting, and functional assays in CRC cell lines.
RESULTS: GABRD was significantly overexpressed in CRC tissues, with elevated levels correlating with advanced disease stages and poorer survival outcomes. Further analysis revealed that GABRD contributes to the establishment of an immunosuppressive tumor microenvironment. Functional assays highlighted GABRD's involvement in key signaling pathways, including Hedgehog, Wnt/β-catenin, and TGF-β, which are pivotal in CRC progression. Knockdown of GABRD significantly inhibited CRC cell proliferation and migration. Molecular docking simulations suggested promising drug repurposing avenues, particularly with afatinib and crizotinib, for GABRD inhibition.
CONCLUSIONS: GABRD gene may serve as a novel biomarker in the diagnosis, prognosis and immune infiltrates of CRC patients.