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新型标志物TNRC6C/AMPD1在胰腺癌微环境中的预后价值及免疫浸润

Prognostic value and immune infiltration of novel markers TNRC6C/AMPD1 in pancreatic cancer microenvironment.

作者信息

Lan Yongting, Du Wenyan, Ma Yongfen, Cao Jingmei

机构信息

Department of Gastroenterology, Zibo Central Hospital, Zibo, 255036, China.

Department of Clinical Laboratory, Zibo Central Hospital, Zibo, 255036, China.

出版信息

Biochem Biophys Rep. 2025 Aug 4;43:102185. doi: 10.1016/j.bbrep.2025.102185. eCollection 2025 Sep.

Abstract

BACKGROUND

Pancreatic cancer (PC) is a highly lethal malignancy with limited treatment options. Identifying novel prognostic biomarkers and therapeutic targets is crucial for improving patient outcomes.

METHODS

A comprehensive bioinformatics analysis was conducted on the Gene Expression Omnibus (GEO, GSE79668, GSE183795) and The Cancer Genome Atlas- Pancreatic Adenocarcinoma (TCGA-PAAD) datasets to identify prognostic biomarkers. The prognostic value of these biomarkers was validated through survival analysis and a Cox proportional hazards model (Cox model). A clinical phenotypic prediction model was constructed using AMPD1 and TNRC6C expression levels, with logistic regression models being built for their combination. The nomogram was constructed to visually represent the model's predictive power. Additionally, immune infiltration and single-cell analyses were performed to explore the underlying mechanisms. Functional experiments were conducted to validate the effects of these biomarkers on PC cell behavior.

RESULTS

Adenosine Monophosphate Deaminase 1 (AMPD1) and Trinucleotide Repeat Containing Adaptor 6C (TNRC6C) were identified as key prognostic biomarkers for PC. High expression of these genes was associated with improved patient survival. Furthermore, AMPD1 and TNRC6C were found to be positively correlated with various immune cells, suggesting their potential role in modulating the tumor immune microenvironment. Functional experiments confirmed that these genes inhibited cancer cell proliferation, migration, invasion, and promoted apoptosis. The prognostic model based on AMPD1 and TNRC6C expression showed significant predictive accuracy, suggesting its potential clinical utility.

CONCLUSION

This study highlights the prognostic significance of AMPD1 and TNRC6C in PC. These findings provide potential new therapeutic targets for PC and warrant further investigation. The developed clinical prediction model further supports their potential utility as biomarkers for patient stratification and prognosis.

摘要

背景

胰腺癌(PC)是一种致死率很高的恶性肿瘤,治疗选择有限。识别新的预后生物标志物和治疗靶点对于改善患者预后至关重要。

方法

对基因表达综合数据库(GEO,GSE79668、GSE183795)和癌症基因组图谱-胰腺腺癌(TCGA-PAAD)数据集进行全面的生物信息学分析,以识别预后生物标志物。通过生存分析和Cox比例风险模型(Cox模型)验证这些生物标志物的预后价值。利用AMPD1和TNRC6C的表达水平构建临床表型预测模型,并建立它们组合的逻辑回归模型。构建列线图以直观展示模型的预测能力。此外,进行免疫浸润和单细胞分析以探索潜在机制。开展功能实验以验证这些生物标志物对PC细胞行为的影响。

结果

单磷酸腺苷脱氨酶1(AMPD1)和含三核苷酸重复序列的衔接蛋白6C(TNRC6C)被确定为PC的关键预后生物标志物。这些基因的高表达与患者生存率提高相关。此外,发现AMPD1和TNRC6C与多种免疫细胞呈正相关,表明它们在调节肿瘤免疫微环境中的潜在作用。功能实验证实这些基因抑制癌细胞增殖、迁移、侵袭并促进细胞凋亡。基于AMPD1和TNRC6C表达的预后模型显示出显著的预测准确性,表明其潜在的临床应用价值。

结论

本研究突出了AMPD1和TNRC6C在PC中的预后意义。这些发现为PC提供了潜在的新治疗靶点,值得进一步研究。所建立的临床预测模型进一步支持了它们作为患者分层和预后生物标志物的潜在应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd92/12374436/3cb443d3681c/gr1.jpg

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