PO.PS01.12 · 人群科学

蛋白质组衰老时钟（PAC）与癌症幸存者的衰弱呈横断面相关：社区动脉粥样硬化风险（ARIC）研究

Proteomic aging clock (PAC) is cross-sectionally associated with frailty in cancer survivors: The Atherosclerosis Risk in Communities (ARIC) study

编号 6260 展板 22 时间 4/21 02:00–05:00 区域 Section 33 主讲 Shuo Wang, MPH;PhD

分会场 Environmental and Occupational Risk Factors, Infection, and Aging

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作者与单位 Authors & Affiliations

Shuo Wang¹, Anne H. Blaes¹, Josef Coresh², Corinne E. Joshu³, James S. Pankow¹, Bharat Thyagarajan¹, Weihua Guan¹, Sanaz Sedaghat¹, Anna Kucharska-Newton⁴, Elizabeth A. Platz³, Anna Prizment¹

¹University of Minnesota, Minneapolis, MN,²New York University Grossman School of Medicine, New York, NY,³Johns Hopkins Bloomberg Sch. of Public Health, Baltimore, MD,⁴University of North Carolina, Chapel Hill, NC

摘要 Abstract

中文摘要

背景：癌症及其治疗诱导的加速衰老导致癌症幸存者中衰弱的患病率高于无癌症个体。癌症幸存者的衰弱给医疗服务提供者带来了重大挑战，因为它增加了不良健康结局的风险并导致高住院率。然而，当前的衰弱评估通常需要在诊所进行面对面评估，这可能耗时且难以实施，尤其是在年长的癌症幸存者中。因此，需要一种能够预测衰弱的生物标志物，以促进该人群的风险分层。我们既往的研究提示PAC可以捕捉癌症幸存者的加速衰老；然而，此前尚无研究检验PAC与癌症幸存者衰弱的关联。本研究考察了一种既往已验证的PAC（Wang等[2025]）与ARIC研究中癌症幸存者衰弱之间的横断面关联。方法：ARIC是一个始于1987年、由白人和黑人男性及女性组成的正在进行的队列。在第5次访视（2011-13年）时，使用SomaScan对3,699名无癌症病史（无癌）受试者和806名癌症幸存者（年龄均为66-90岁）测量了5,000种血浆蛋白。我们此前在67%随机选取的无癌受试者中创建了一个PAC，并在ARIC内部及另一大型队列外部对其进行了验证。我们在将PAC对实际年龄进行回归后计算了年龄加速（PAC-accel）。在第5次访视时，ARIC使用累积衰弱指数（FI）和Fried衰弱表型（FFP）评估了衰弱。我们使用线性回归（针对FI）和逻辑回归（针对FFP，衰弱与前衰弱 vs 健壮）考察了PAC-accel与癌症幸存者（癌症诊断后）衰弱的横断面关联。所有关联均针对实际年龄、性别、种族、教育、BMI、吸烟状况、糖尿病、心血管疾病和eGFR进行了校正。结果：在我们的研究中，癌症幸存者的平均FI（SD）为0.21（0.10），其中57.8%为衰弱或前衰弱。考虑最常见的癌症（肺癌、结直肠癌、乳腺癌、前列腺癌），肺癌幸存者的平均FI以及衰弱与前衰弱幸存者的比例均最高（0.28（0.10）和80%）。在所有癌症幸存者中，PAC-accel（每5年）与FI（差异 = 0.04，95% CI 0.03-0.05）和FFP（OR = 2.56，95% CI 1.77-3.70）均呈横断面相关。样本量有限使得无法按癌症类型考察与衰弱的关联。结论：我们的发现提示PAC与衰弱之间存在横断面关联。我们的下一步是考察PAC是否与未来的衰弱风险相关。这项研究将有助于确定PAC是否有望成为临床环境中年长癌症幸存者衰弱风险分层的工具。资助：NHLBI、NCI、NPCR

查看英文原文 English abstract

Background: Accelerated aging induced by cancer and its treatment contributes to a higher prevalence of frailty in cancer survivors than individuals without cancer. Frailty in cancer survivors poses significant challenges for healthcare providers, as it increases the risk of adverse health outcomes and leads to high rates of hospitalization. However, current frailty assessments often require in-person evaluations in clinics, which can be time-consuming and difficult to perform, particularly in older cancer survivors. Therefore, a biomarker that could predict frailty is needed to facilitate risk stratification in this population. Our previous study suggested that PACs could capture accelerated aging in cancer survivors; however, no previous studies have tested PACs' associations with frailty in cancer survivors. This study examined the cross-sectional associations of a previously validated PAC (Wang et al. [2025]) with frailty in cancer survivors in the ARIC study. Methods: ARIC is an ongoing cohort of White and Black men and women initiated in 1987. At Visit 5 (2011-13), 5,000 plasma proteins were measured using SomaScan in 3,699 participants without a history of cancer (cancer-free) and 806 cancer survivors, all aged 66-90. We previously created a PAC in 67% of randomly selected cancer-free participants and validated it internally in ARIC and externally in another large cohort. We calculated age acceleration after regressing PAC on chronological age (PAC-accel). At Visit 5, ARIC assessed frailty using the cumulative frailty index (FI) and the Fried Frailty Phenotype (FFP). We examined the cross-sectional associations of PAC-accel with frailty in cancer survivors (after cancer diagnosis), using linear regression for FI and logistic regression for FFP (Frail & Pre-frail vs. Robust). All associations were adjusted for chronological age, sex, race, education, BMI, smoking status, diabetes, cardiovascular disease, and eGFR. Results: In our study, cancer survivors had a mean FI (SD) of 0.21 (0.10), and 57.8% of them were either frail or pre-frail. Considering the most common cancers (lung, colorectal, breast, prostate), both mean FI and the proportion of frail & pre-frail cancer survivors were highest among lung cancer survivors (0.28 (0.10) and 80%). In all cancer survivors, PAC-accel (per 5 years) was cross-sectionally associated with both FI (difference = 0.04, 95% CI 0.03-0.05) and FFP (OR = 2.56, 95% CI 1.77-3.70). Limited sample size precluded examining associations with frailty by cancer type. Conclusion: Our findings suggest a cross-sectional association of PAC with frailty. Our next step is to examine whether PAC is associated with future frailty risk. This research will help determine whether PAC holds promise as a tool for frailty risk stratification among older cancer survivors in clinical settings. Funding: NHLBI, NCI, NPCR

利益披露 Disclosure

S. Wang, None.. A. H. Blaes, None.. J. Coresh, None.. J. S. Pankow, None.. B. Thyagarajan, None.. W. Guan, None.. S. Sedaghat, None.. A. Kucharska-Newton, None.. A. Prizment, None.

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