生长分化因子15和脂质运载蛋白2用于胰腺癌的早期检测和预后评估

GDF15 and LCN2 for early detection and prognosis of pancreatic cancer.

作者信息

Zhu Xinxia, Olson Brennan, Keith Dove, Norgard Mason A, Levasseur Peter R, Diba Parham, Protzek Sara, Li Ju, Li Xiaolin, Korzun Tetiana, Sattler Ariana L, Buenafe Abigail C, Grossberg Aaron J, Marks Daniel L

机构信息

Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland, Oregon, USA; Brenden-Colson Center for Pancreatic Care, Oregon Health & Science University, Portland, Oregon, USA.

Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland, Oregon, USA; Medical Scientist Training program, Oregon Health & Science University, Portland, Oregon, USA; Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, Minnesota, USA.

出版信息

Transl Oncol. 2024 Dec;50:102129. doi: 10.1016/j.tranon.2024.102129. Epub 2024 Sep 30.

DOI:10.1016/j.tranon.2024.102129

PMID:39353236

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11474189/

Abstract

BACKGROUND

The prognosis of pancreatic ductal adenocarcinomas (PDAC) remains very poor, emphasizing the critical importance of early detection, where biomarkers offer unique potential. Although growth differentiation factor 15 (GDF15) and Lipocalin 2 (LCN2) have been linked to PDAC, their precise roles as biomarkers are uncertain.

METHODS

Circulating levels of GDF15 and LCN2 were examined in human PDAC patients, heathy controls, and individuals with benign pancreatic diseases. Circulating levels of IL-6, CA19-9, and neutrophil-to-lymphocyte ratio (NLR) were measured for comparisons. Correlations between PDAC progression and overall survival were assessed. A mouse PDAC model was employed for comprehensive analyses, complementing the human studies by exploring associations with various metabolic and inflammatory parameters. Sensitivity and specificity of the biomarkers were evaluated.

FINDINGS

Our results demonstrated elevated levels of circulating GDF15 and LCN2 in PDAC patients compared to both healthy controls and individuals with benign pancreatic diseases, with higher GDF15 levels associated with disease progression and increased mortality. In PDAC mice, circulating GDF15 and LCN2 progressively increased, correlating with tumor growth, behavioral manifestations, tissue and molecular pathology, and cachexia development. GDF15 exhibited highly sensitive and specific for PDAC patients compared to CA19-9, IL-6, or NLR, while LCN2 showed even greater sensitivity and specificity in PDAC mice. Combining GDF15 and LCN2, or GDF15 and CA19-9, enhanced sensitivity and specificity.

INTERPRETATION

Our findings indicate that GDF15 holds promise as a biomarker for early detection and prognosis of PDAC, while LCN2 could strengthen diagnostic panels.

摘要

背景

胰腺导管腺癌（PDAC）的预后仍然很差，这凸显了早期检测的至关重要性，而生物标志物具有独特的潜力。尽管生长分化因子15（GDF15）和脂质运载蛋白2（LCN2）与PDAC有关，但其作为生物标志物的确切作用尚不确定。

方法

检测了人类PDAC患者、健康对照者以及患有良性胰腺疾病个体的循环GDF15和LCN2水平。测量了IL-6、CA19-9的循环水平以及中性粒细胞与淋巴细胞比值（NLR）以作比较。评估了PDAC进展与总生存期之间的相关性。采用小鼠PDAC模型进行综合分析，通过探索与各种代谢和炎症参数的关联来补充人体研究。评估了生物标志物的敏感性和特异性。

研究结果

我们的结果表明，与健康对照者和患有良性胰腺疾病的个体相比，PDAC患者的循环GDF15和LCN2水平升高，GDF15水平越高与疾病进展和死亡率增加相关。在PDAC小鼠中，循环GDF15和LCN2逐渐升高，与肿瘤生长、行为表现、组织和分子病理学以及恶病质发展相关。与CA19-9、IL-6或NLR相比，GDF15对PDAC患者表现出高度的敏感性和特异性，而LCN2在PDAC小鼠中表现出更高的敏感性和特异性。联合使用GDF15和LCN2，或GDF15和CA19-9，可提高敏感性和特异性。