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NR4A1 as a potential therapeutic target in colon adenocarcinoma: a computational analysis of immune infiltration and drug response.

ABSTRACT: Background: Colon adenocarcinoma (COAD) is a common malignancy with high morbidity and mortality rates. The immune system plays a crucial role in CRC development and progression, making it a potential therapeutic target. In this study, we analyzed transcriptomic data from CRC patients to investigate immune infiltration and identify potential therapeutic targets. Method and results: we used CIBERSORT to analyze the immune infiltration in COAD samples and found that the high infiltration of M2 macrophages and neutrophils was associated with poor prognosis. Next, we identified NR4A1 as a potential therapeutic target based on its protective effect in two predict models. Using cancer therapeutics response analysis, we found that high expression levels of NR4A1 were sensitive to OSI-930, a tyrosine kinase inhibitor with anti-tumor effects. Conclusion: Our findings suggest that targeting NR4A1 with OSI-930 may be a promising therapeutic strategy for COAD patients with high levels of immune infiltration. However, further studies are needed to investigate the clinical efficacy of this approach.

SUBMITTER: Li M

PROVIDER: S-EPMC10410285 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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NR4A1 as a potential therapeutic target in colon adenocarcinoma: a computational analysis of immune infiltration and drug response.

Li Mei M Zhang Zhongyi Z Li Mingzhou M Chen Zhe Z Tang Weizhu W Cheng Xiang X

Frontiers in genetics 20230726

<b>Background:</b> Colon adenocarcinoma (COAD) is a common malignancy with high morbidity and mortality rates. The immune system plays a crucial role in CRC development and progression, making it a potential therapeutic target. In this study, we analyzed transcriptomic data from CRC patients to investigate immune infiltration and identify potential therapeutic targets. <b>Method and results:</b> we used CIBERSORT to analyze the immune infiltration in COAD samples and found that the high infiltra ...[more]

PMID: 37564873

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Project description:BackgroundThe current study aimed to investigate the interrelation between P2RY14 and the prognosis of patients suffering from lung adenocarcinoma (LUAD) following surgery.MethodsThe differentially expressed gene (DEG) P2RY14 was screened by the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and Immunology Database and Analysis Portal (ImmPort) databases. The relationship between P2RY14 and clinical data of LUAD was analyzed in TCGA and Kaplan-Meier (KM)-plotter databases. The association of P2RY14 with immune cells and immune-related expressed genes was analyzed in the Tumor Immune Estimation Resource (TIMER) database. A retrospective analysis of the 100 patients clinical data undergoing pulmonary adenocarcinoma surgery admitted to Nanjing Chest Hospital. Immunohistochemistry (IHC) analysis was carried out to evaluate the P2RY14 expression in lung cancer tissues, and quantitative reverse transcription PCR (RT-qPCR) was used to confirm the mRNA expression of this gene in LUAD tissues. And their survival was evaluated. KM method and the log-rank test were used for univariate survival analysis, and the Cox regression method was employed for multivariate survival analysis.ResultsP2Y14 was the DEG identified by the database. P2Y14 expression was upregulated in para-cancer tissues in comparison to cancer tissues. Patients suffering from LUAD who have high P2RY14 expression had a better prognosis than those with low expression. P2RY14 expression was shown to be substantially linked with immune invasion in the TIMER database. Finally, the trial included 100 patients, of which 80 died and 20 survived with a mean overall survival (OS) of 48 months. Between the high and low expression groups of P2RY14, there were statistically significant variations in the clinical stage and differentiation degree (P<0.05). Cox regression analysis revealed that differentiation degree, smoking history, and P2RY14 expression were independent risk factors for the prognosis of LUAD patients (all P<0.05).ConclusionsP2RY14 can substantially prolong the OS of patients suffering from LUAD and can be utilized as a new LUAD predictive biomarker. P2RY14 may be related to LUAD immune invasion and have an essential role in inhibiting tumor cell immune escape within the LUAD microenvironment.

Project description:Background: Epithelial-mesenchymal transition (EMT) is closely associated with cancer cell metastasis. Colon adenocarcinoma (COAD) is one of the most common malignancies in the world, and its metastasis leading to poor prognosis remains a challenge for clinicians. The purpose of this study was to explore the prognostic value of EMT-related genes (EMTRGs) by bioinformatics analysis and to develop a new EMTRGs prognostic signature for COAD. Methods: The TCGA-COAD dataset was downloaded from the TCGA portal as the training cohort, and the GSE17538 and GSE29621 datasets were obtained from the GEO database as the validation cohort. The best EMTRGs prognostic signature was constructed by differential expression analysis, Cox, and LASSO regression analysis. Gene set enrichment analysis (GSEA) is used to reveal pathways that are enriched in high-risk and low-risk groups. Differences in tumor immune cell levels were analyzed using microenvironmental cell population counter and single sample gene set enrichment analysis. Subclass mapping analysis and Genomics of Drug Sensitivity in Cancer were applied for prediction of immunotherapy response and chemotherapy response, respectively. Results: A total of 77 differentially expressed EMTRGs were identified in the TCGA-COAD cohort, and they were significantly associated with functions and pathways related to cancer cell metastasis, proliferation, and apoptosis. We constructed EMTRGs prognostic signature with COMP, MYL9, PCOLCE2, SCG2, and TIMP1 as new COAD prognostic biomarkers. The high-risk group had a poorer prognosis with enhanced immune cell infiltration. The GSEA demonstrated that the high-risk group was involved in "ECM Receptor Interaction," "WNT Signaling Pathway" and "Colorectal Cancer." Furthermore, patients with high risk scores may respond to anti-CTLA4 therapy and may be more resistant to targeted therapy agents BI 2536 and ABT-888. Conclusion: Together, we developed a new EMTRGs prognostic signature that can be an independent prognostic factor for COAD. This study has guiding implications for individualized counseling and treatment of COAD patients.

Dataset Information

NR4A1 as a potential therapeutic target in colon adenocarcinoma: a computational analysis of immune infiltration and drug response.

Publications

NR4A1 as a potential therapeutic target in colon adenocarcinoma: a computational analysis of immune infiltration and drug response.

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