Data from PRECISE: A Prognostic Thyrocyte-Derived Gene Signature for Papillary Thyroid Carcinoma

作者：Sophie H. Li, Chia-Chin Wu, Vicente Rodrigues Marczyk, Matthew A. Loberg, Aatish Thennavan, Maxime Tarabichi, Li Xu, Ying C. Henderson, Meghan E. Martin, Tuan M. Tran, Dzifa Y. Duose, Steven Alexander, Rajyalakshmi Luthra, Quanhu Sheng, George Jing Xu, Eric C. Huang, Marie-Claude C. Hofmann, Xiao Ling Zhao, Stephen Yenzen Lai, S. Mohsen Hosseini, Michelle D. Williams, Wenyi Wang, Sarah Hamidi, Mark Zafereo, Maria E. Cabanillas, Nicholas E. Navin, Vivian Lee Weiss, Jennifer Rui Wang · 年份：2026 · DOI：10.1158/1078-0432.c.8568781 · 研究领域：Thyroid Cancer Diagnosis and Treatment、Single-cell and spatial transcriptomics、Ferroptosis and cancer prognosis

AbstractPurpose: Papillary thyroid carcinoma (PTC) exhibits heterogeneous behavior, underscoring the need for effective biomarkers and improved risk stratification methods. We developed a thyrocyte-derived gene signature, Prognostic RNA Expression Cell-specific Integrated Signature (PRECISE), using single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq) and evaluated its prognostic utility across cohorts. Experimental Design: PRECISE was developed using a discovery cohort of patients with PTC [MD Anderson Cancer Center (MDACC), n = 109, median follow-up = 14 years]. Within the cohort, 11 PTC tumors and 4 normal thyroid samples were successfully sequenced using snRNA-seq. Differentially expressed genes were integrated with previously identified thyrocyte-associated genes from scRNA-seq. Prognostic significance was assessed using bulk RNA-seq in the discovery cohort and validated in two additional cohorts [Vanderbilt University Medical Center (VUMC), n = 65; The Cancer Genome Atlas (TCGA), n = 370]. A rank-based single-sample method was used for score calculation. Associations between PRECISE and progression-free survival (PFS) and disease-specific survival (DSS) were evaluated using multivariate Cox models, and predictive models were compared using Harrell’s C-statistic and likelihood ratio tests. Results: PRECISE is comprised of 41 epithelial genes downregulated in PTC tumor cells. Higher PRECISE was significantly associated with shorter PFS acros...