Establishing a new-onset diabetes-related metabolism signature for predicting the prognosis and immune landscape in pancreatic cancer.

IF 3.3 3区医学 Q2 ONCOLOGY Carcinogenesis Pub Date : 2024-11-11 DOI:10.1093/carcin/bgae072

Yilei Yang, Luyao Liu, Haochen Cui, Bin Cheng, Wang Peng, Ronghua Wang, Jinlin Wang, Wei Chen, Mengdie Cao, Yanling Li, Jingwen Liang, Shiru Chen, Shuya Bai, Yuchong Zhao

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Abstract

New-onset diabetes (NOD) is a common condition among patients with pancreatic adenocarcinoma (PAAD) and is related to poor clinical outcomes. The potential impact of NOD on PAAD progression and the tumor microenvironment remains unclear. Here, we revealed that NOD in PAAD was associated with metabolic disorders. Utilizing three machine learning algorithms, a new-onset diabetes-related metabolism signature (NRMS) was established. Validated in three independent cohorts, patients with a high NRMS score exhibited worse prognosis. Moreover, an elevated NRMS score was associated with an immunosuppressive microenvironment and diminished response to immunotherapy. Further experiments demonstrated that ALDH3A1, a key feature in NRMS, was significantly up-regulated in tissues from PAAD patients with NOD and played a crucial role in tumor progression and immune suppression. Our findings highlight the potential of NRMS as a prognostic biomarker and an indicator of immunotherapy response for patients with PAAD.

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建立新发糖尿病相关代谢特征，用于预测胰腺癌的预后和免疫状况。

新发糖尿病（NOD）是胰腺腺癌（PAAD）患者中的常见病，与不良的临床预后有关。NOD对PAAD进展和肿瘤微环境的潜在影响仍不清楚。在这里，我们发现 PAAD 中的 NOD 与代谢紊乱有关。利用三种机器学习算法，建立了新发糖尿病相关代谢特征（NRMS）。经三个独立队列验证，NRMS评分高的患者预后较差。此外，NRMS评分升高与免疫抑制微环境和免疫疗法反应减弱有关。进一步的实验表明，ALDH3A1 是 NRMS 的一个关键特征，在 PAAD NOD 患者的组织中明显上调，并在肿瘤进展和免疫抑制中发挥关键作用。我们的研究结果凸显了 NRMS 作为 PAAD 患者预后生物标志物和免疫疗法反应指标的潜力。

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来源期刊

Carcinogenesis 医学-肿瘤学

CiteScore

9.20

自引率

2.10%

发文量

审稿时长

1 months

期刊介绍： Carcinogenesis: Integrative Cancer Research is a multi-disciplinary journal that brings together all the varied aspects of research that will ultimately lead to the prevention of cancer in man. The journal publishes papers that warrant prompt publication in the areas of Biology, Genetics and Epigenetics (including the processes of promotion, progression, signal transduction, apoptosis, genomic instability, growth factors, cell and molecular biology, mutation, DNA repair, genetics, etc.), Cancer Biomarkers and Molecular Epidemiology (including genetic predisposition to cancer, and epidemiology), Inflammation, Microenvironment and Prevention (including molecular dosimetry, chemoprevention, nutrition and cancer, etc.), and Carcinogenesis (including oncogenes and tumor suppressor genes in carcinogenesis, therapy resistance of solid tumors, cancer mouse models, apoptosis and senescence, novel therapeutic targets and cancer drugs).