PO.PS01.01 · 人群科学
胃癌前病变的自然史与生物标志物发现：来自 TUMMIE 纵向研究的见解
Natural history and biomarker discovery in gastric preneoplasia: Insights from the TUMMIE longitudinal study
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：胃癌仍是全球癌症死亡的主要原因之一，其发病率和结局存在显著的种族和民族差异。胃肠上皮化生（GIM）是一种关键的癌前病变，但其自然史和进展生物标志物尚不清楚，尤其是在美国多样化人群中。
方法：TUMMIE 研究是加州大学戴维斯分校健康中心胃癌前病变患者的纵向队列。在试点阶段，我们纳入了 69 名经组织学确诊为 GIM 的个体（平均年龄 66 岁）。队列人口构成为 67% 女性和 33% 男性，种族/民族分布为 67% 非西班牙裔白人、15% 亚裔、7% 黑人、7% 西班牙裔白人，以及 4% 多种族、夏威夷原住民/其他太平洋岛民或缺失。其中 22 名患者（32%）报告有个人癌症史，近半数（48%）报告有胃部疾病家族史。在这些人中，39 名参与者提供了粪便和唾液样本，采用数字微滴 PCR（ddPCR）分析幽门螺杆菌（H. pylori）菌株检测。我们评估了两种样本类型中临床检测与基于 ddPCR 检测之间的一致性。此外，我们对已发表的与胃癌前病变进展相关的生物标志物进行了范围综述。
结果：在 39 名生物样本捐献者中，8 人经 ddPCR 检测 H. pylori 呈高阳性。菌株分型揭示了 H. pylori 毒力谱的明显差异，ddPCR 在参与者中检测到 CagA 阳性和 CagA 阴性菌株，包括若干具有强高微滴信号（>100 至 >1000）的样本，从而表明队列中存在菌株多样性。ddPCR 检测到克拉霉素耐药突变，这表明存在抗生素耐药和抗生素敏感的 H. pylori 菌株。若干样本携带 VacA 毒素相关等位基因和 EPIYA 基序。初步分析显示 ddPCR 检测与临床检测结果之间存在相关性。人口特征和感染率在不同种族/民族群体间存在差异，凸显了风险谱中潜在的差异。范围综述识别了与炎症、免疫反应和上皮转化相关通路中的候选生物标志物。
结论：本试点阶段证明了在患有 GIM 的多民族队列中进行生物样本采集和分子表征的可行性。整合基于 ddPCR 的 H. pylori 检测和生物标志物发现，可为胃癌预防的风险分层和监测策略提供依据。扩大的纵向随访将能够验证进展生物标志物，并阐明疾病轨迹中的种族/民族差异。
查看英文原文 English abstract
Background: Gastric cancer remains a leading cause of cancer mortality worldwide, with marked racial and ethnic disparities in incidence and outcomes. Gastric intestinal metaplasia (GIM) is a key preneoplastic lesion, yet its natural history and progression biomarkers are poorly understood, particularly in diverse U.S. populations.
Methods: The TUMMIE study is a longitudinal cohort of patients with gastric preneoplasia at UC Davis Health. In a pilot phase, we enrolled 69 individuals (mean age 66 years) with histologically confirmed GIM. The cohort demographic composition was 67% female and 33% male, with race/ethnicity distributed as 67% non-Hispanic White, 15% Asian, 7% Black, 7% Hispanic White, and 4% multiracial, Native Hawaiian/Other Pacific Islander, or missing. Twenty-two patients (32%) reported a personal history of cancer and nearly half (48%) reported a family history of gastric conditions.. Among these, 39 participants provided stool and saliva samples, which were analyzed for Helicobacter pylori (H. pylori) strain detection using digital droplet PCR (ddPCR). We assessed concordance between clinical testing and ddPCR-based detection in both sample types. Additionally, we conducted a scoping review of published biomarkers associated with gastric preneoplasia progression.
Results: Of the 39 biospecimen donors, 8 tested high positive for H. pylori by ddPCR. Strain typing revealed clear variation in H. pylori virulence profiles, with ddPCR detecting both CagA-positive and CagA-negative strains across participants, including several samples with strong high-droplet signals (>100 to >1000) thereby indicating strain diversity in the cohort. Clarithromycin resistance mutations were detected by ddPCR, this indicates the presence of both antibiotic-resistant and antibiotic-sensitive H. pylori strains. Several samples carried VacA toxin-associated alleles and EPIYA motifs. Preliminary analyses show correlations between ddPCR detection and clinical test results. Demographic characteristics and infection rates varied across racial/ethnic groups, highlighting potential disparities in risk profiles. The scoping review identified candidate biomarkers in pathways related to inflammation, immune response, and epithelial transformation.
Conclusions: This pilot phase demonstrates feasibility of biospecimen collection and molecular characterization in a multiethnic cohort with GIM. Integration of ddPCR-based H. pylori detection and biomarker discovery may inform risk stratification and surveillance strategies for gastric cancer prevention. Expanded longitudinal follow-up will enable validation of progression biomarkers and clarify racial/ethnic differences in disease trajectory.
利益披露 Disclosure
T. A. Simi, None..
F. Leonardo Castro Valencia, None..
N. Chavarria Villa, None..
A. Michelle Rolon, None..
K. Jagasia, None..
A. Zhornitskiy, None..
A. Gupta Cogdill, None..
J. Zheng-Hsien Ko, None..
J. Marsano, None.