通过单细胞转录组学分析揭示MDK-SDC4相互作用在胰腺癌相关新发糖尿病中的作用

IF 14.3 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Zengyu Feng, Jianyao Lou, Chuanshuai Lin, Haocheng Yu, Yuheng Tu, Jiali Gong, Xiawei Li, Yulian Wu
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引用次数: 0

摘要

血糖水平升高可能是潜在胰腺癌的早期指标。区分胰腺癌相关的新发糖尿病(PCAND)和新发2型糖尿病(T2DM)有望实现胰腺癌的早期诊断。然而,仍然缺乏有效的生物标志物来区分PCAND和更普遍的新发T2DM,主要是因为PCAND的发病机制难以捉摸。在这项研究中,通过单细胞RNA测序全面阐明了复杂的细胞间通讯。研究结果确定了Midkine (MDK)作为肿瘤和β细胞之间相互作用的潜在介质。MDK来源于胰腺导管腺癌细胞,通过与β细胞表面的SDC4受体结合,下调Ras信号通路,对副肿瘤β细胞产生有害影响,从而损害胰岛素的产生和分泌。值得注意的是,PCAND患者的血浆MDK水平高于T2DM患者。总之,MDK已成为PCAND发病机制的关键驱动因素,并可能作为一种基于血液的生物标志物,在新发糖尿病人群中区分PCAND和T2DM,从而促进胰腺癌早期检测策略的发展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Unraveling the Role of MDK-SDC4 Interaction in Pancreatic Cancer-Associated New-Onset Diabetes by Single-Cell Transcriptomic Analysis.

Elevated blood glucose levels may serve as an early indicator of underlying pancreatic cancer. Discriminating between pancreatic cancer-associated new-onset diabetes (PCAND) and new-onset type 2 diabetes mellitus (T2DM) holds promise for enabling an earlier diagnosis of pancreatic cancer. Nevertheless, the absence of effective biomarkers for distinguishing PCAND from the more prevalent new-onset T2DM persists, primarily because of the elusive pathogenesis of PCAND. In this study, the intricate intercellular communication is comprehensively elucidated through single-cell RNA sequencing. The findings identified Midkine (MDK) as a potential mediator of the interaction between tumor and beta cells. MDK, which originated from pancreatic ductal adenocarcinoma cells, exerted deleterious effects on paraneoplastic beta cells by binding to the SDC4 receptor on the beta cell surface and subsequently downregulating the Ras signaling pathway, thereby impairing insulin production and secretion. Notably, the plasma levels of MDK are higher in patients with PCAND than in those with T2DM. In conclusion, MDK has emerged as a pivotal driver of PCAND pathogenesis and may function as a blood-based biomarker for discriminating between PCAND and T2DM in populations with new-onset diabetes, thereby facilitating the advancement of early detection strategies for pancreatic cancer.

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来源期刊
Advanced Science
Advanced Science CHEMISTRY, MULTIDISCIPLINARYNANOSCIENCE &-NANOSCIENCE & NANOTECHNOLOGY
CiteScore
18.90
自引率
2.60%
发文量
1602
审稿时长
1.9 months
期刊介绍: Advanced Science is a prestigious open access journal that focuses on interdisciplinary research in materials science, physics, chemistry, medical and life sciences, and engineering. The journal aims to promote cutting-edge research by employing a rigorous and impartial review process. It is committed to presenting research articles with the highest quality production standards, ensuring maximum accessibility of top scientific findings. With its vibrant and innovative publication platform, Advanced Science seeks to revolutionize the dissemination and organization of scientific knowledge.
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