PO.BCS01.16 · 生物信息与计算

PRECISE：一种用于甲状腺乳头状癌的预后性甲状腺滤泡细胞来源基因特征

PRECISE: A prognostic thyroid follicular cell-derived gene signature for papillary thyroid carcinoma

编号 2709 展板 2 时间 4/20 02:00–05:00 区域 Section 2 主讲 Jennifer Wang, MD

分会场 Integration of Clinical and Research Data

查看 PDF 下载 PDF 🔒 查看 / 下载完整 PDF 需登录并开通下载套餐 · 查看套餐 / 开通 AACR 官方页面

作者与单位 Authors & Affiliations

Sophie Li¹, Chia C. Wu¹, Vicente R. Marczyk¹, Matthew A. Loberg², Aatish Thennavan³, Maxime Tarabichi⁴, Li Xu¹, Ying C. Henderson¹, Tuan M. Tran³, Quanhu Sheng⁵, George J. Xu², Eric C. Huang⁶, Marie-Claude Hofmann⁷, Xiao Zhao¹, Stephen Y. Lai¹, Michelle D. Williams⁸, Wenyi Wang⁹, Sarah Hamidi⁷, Mark E. Zafereo¹, Maria E. Cabanillas⁷, Nicholas E. Navin³, Vivian L. Weiss², Jennifer R. Wang¹

¹Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer, Houston, TX,²Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN,³Department of Systems Biology, The University of Texas MD Anderson Cancer, Houston, TX,⁴Institute for Interdisciplinary Research (IRIBHM) – Jacques E. Dumont, Université Libre de Bruxelles, Brussels, Belgium,⁵Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN,⁶Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA,⁷Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer, Houston, TX,⁸Department of Pathology, The University of Texas MD Anderson Cancer, Houston, TX,⁹Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer, Houston, TX

摘要 Abstract

中文摘要

目的：甲状腺乳头状癌（PTC）表现出异质性行为。PTC亟需有效的生物标志物和改进的风险分层方法。源自整体RNA测序的基因特征捕获的是复合转录谱，会受到肿瘤微环境细胞的混杂影响。我们利用单细胞和单核RNA测序技术，开发了一种甲状腺滤泡细胞来源的基因特征—预后性RNA表达细胞特异性整合特征（Prognostic RNA Expression Cell-specific Integrated SignaturE，PRECISE），并评估了其在独立队列中的预后效用。实验流程：PRECISE使用一个PTC患者发现队列（MDACC n=109）开发，中位随访时间为14年。在该队列中，11例PTC肿瘤和4例正常甲状腺样本成功进行了单核RNA测序。将恶性细胞中相较于正常甲状腺滤泡细胞显著下调的基因，与此前通过单细胞RNA测序识别的差异表达基因相整合。使用发现队列中的整体RNA测序评估预后意义，并在另外2个队列中进行验证（VUMC n=65；TCGA n=370）。采用基于秩的单样本方法进行评分计算。使用多变量Cox比例风险模型评估PRECISE评分与无进展生存（PFS）和疾病特异性生存（DSS）之间的关联，并使用Harrell's C统计量和方差分析（ANOVA）比较预测模型。结果：PRECISE由41个在PTC肿瘤细胞中下调、在正常滤泡细胞中上调的基因组成，捕获了甲状腺功能和代谢通路的失调。较高的PRECISE评分在全部3个队列中均与更短的PFS显著相关（MDACC HR=1.64，P=0.002；VUMC HR=2.54，P<0.001；TCGA HR=1.63，P=0.012），并在两个随访时间≥5年的队列中经TNM分期调整后仍保持显著（MDACC aHR=1.42，P=0.038；VUMC aHR=2.12，P=0.024）。PRECISE评分在这些队列中也与DSS相关（MDACC HR=4.16，P<0.001；VUMC HR=2.23，P=0.01），且在MDACC队列中独立于TNM分期（aHR=2.83，P=0.015）。纳入PRECISE在基于分期的模型之外显著改善了对PFS（MDACC P=0.031；VUMC P=0.024）和DSS（MDACC P=0.008）的预测性能。结论：PRECISE是一种甲状腺上皮基因来源的特征，在PTC中具有独立的预后价值。

查看英文原文 English abstract

Purpose: Papillary thyroid carcinoma (PTC) exhibits heterogeneous behavior. There is a need for effective biomarkers and improved risk stratification methods in PTC. Gene signatures derived from bulk RNA sequencing capture composite transcriptional profiles that are confounded by tumor microenvironment cells. We developed a thyroid follicular cell-derived gene signature, P rognostic R NA E xpression C ell-specific I ntegrated S ignaturE (PRECISE), using single-cell and nucleus RNA sequencing techniques and evaluated its prognostic utility across independent cohorts. Experimental Procedures: PRECISE was developed using a discovery cohort of PTC patients (MDACC n=109) with a median follow-up of 14 years. Within the cohort, 11 PTC tumors and 4 normal thyroid samples were successfully sequenced using single-nucleus RNA sequencing. Genes that were significantly downregulated in malignant cells compared to normal thyroid follicular cells were integrated with previously identified differentially expressed genes from single-cell RNA sequencing. Prognostic significance was assessed using bulk RNA sequencing in the discovery cohort and validated in 2 additional cohorts (VUMC n=65; TCGA n=370). A rank-based single-sample method was used for score calculation. Associations between PRECISE score and progression-free (PFS) and disease-specific survival (DSS) were evaluated using multivariate Cox proportional hazards models, and predictive models were compared using Harrell's C-statistic and ANOVA. Results: PRECISE comprised of 41 genes downregulated in PTC tumor cells and upregulated in normal follicular cells, capturing dysregulation of thyroid function and metabolism pathways. Higher PRECISE score was significantly associated with shorter PFS across all 3 cohorts (MDACC HR=1.64, P =0.002; VUMC HR=2.54, P <0.001; TCGA HR=1.63, P =0.012) and remained significant after TNM stage adjustment in two cohorts with ≥5 years follow-up (MDACC aHR=1.42, P =0.038; VUMC aHR=2.12, P =0.024). PRECISE score was also associated with DSS in these cohorts (MDACC HR=4.16, P <0.001; VUMC HR=2.23, P =0.01), independent of TNM stage in the MDACC cohort (aHR=2.83, P =0.015). Incorporating PRECISE significantly improved predictive performance for PFS (MDACC P =0.031; VUMC P =0.024) and DSS (MDACC P =0.008) beyond stage-based models. Conclusions: PRECISE is a thyroid epithelial gene-derived signature with independent prognostic value in PTC.

利益披露 Disclosure

S. Li, None.. C. C. Wu, None.. V. R. Marczyk, None.. M. A. Loberg, None.. A. Thennavan, None.. M. Tarabichi, None.. L. Xu, None.. Y. C. Henderson, None.. T. M. Tran, None.. Q. Sheng, None.. G. J. Xu, None.. E. C. Huang, None.. M. Hofmann, None.. X. Zhao, None.. S. Y. Lai, None.. M. D. Williams, None.. W. Wang, None.. S. Hamidi, None.. M. E. Zafereo, None.. M. E. Cabanillas, None.. N. E. Navin, None.. V. L. Weiss, None.. J. R. Wang, None.

← 返回 AACR 2026 检索