Dataset Information

Integrative Proteogenomic Characterization Reveals Therapeutic Targets in Poorly Differentiated and Anaplastic Thyroid Cancers

ABSTRACT: In our study, we constructed a multicenter thyroid-cancer cohort consisting of 467 formalin-fixed paraffin-embedded (FFPE) samples, among which WES, proteome, and phosphorylated proteome analysis were conducted. Thyroid tumors consisted of 124 ATC samples, 47 PDTC samples and 177 PTC samples (including 3 biological replications).The 119 NATs were derived from tumor-adjacent tissues of 20 ATC patients and 99 PTC patients. Phosphoproteomic analysis was performed on 63 ATCs, 25 PDTCs, and 81 PTCs. 48 NAT samples were determined from tumor-adjacent tissues of 20 ATC patients and 28 PTC patients.

ORGANISM(S): Homo Sapiens

SUBMITTER: Minghua Ge

PROVIDER: PXD054521 | iProX | Sun Mar 16 00:00:00 GMT 2025

REPOSITORIES: iProX

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Integrative proteogenomic characterization reveals therapeutic targets in poorly differentiated and anaplastic thyroid cancers.

Pan Zongfu Z Tan Zhuo Z Xu Ning N Yao Zhenmei Z Zheng Chuanming C Shang Jinbiao J Xie Lei L Xu Jiajie J Wang Jiafeng J Jiang Liehao L Zhu Xuhang X Yu Dingyi D Li Ying Y Che Yulu Y Gong Yingying Y Qin Zhaoyu Z Zhang Yiwen Y Zou Xiaozhou X Xu Tong T Guo Zhenying Z Jin Tiefeng T Guo Tiannan T Wang Wei W Chen Wanyuan W Sun Yaoting Y Wang Weixin W Peng Xiaojun X Yin Changtian C Ding Chen C Huang Ping P Ge Minghua M

Nature communications 20250416 1

Poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) present major challenges in treatment owing to extreme aggressiveness and high heterogeneity. In this study, deep-scale analyses spanning genomic, proteomic, and phosphoproteomic data are performed on 348 thyroid-cancer and 119 tumor-adjacent samples. TP53 (48%), TERT promoter (36.5%), and BRAF (23%) are most frequently mutated in PDTC and ATC. Ribosome biogenesis is identified as a common hallmark of ATC, and RRP9 s ...[more]

PMID: 40234451

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Project description:The biology underlying nodal metastasis is poorly understood. Transcriptome profiling has helped to characterize both primary tumors seeding nodal metastasis and the metastasis themselves. The interpretation of these data, however, is not without ambiguities. Here we profiled the transcriptomes of 17 papillary thyroid cancer (PTC) nodal metastases, associated primary tumors and primary tumors from N0 patients. We also included patient-matched normal thyroid and lymph node samples as controls to address some limits of previous studies. We found that the transcriptomes of patient-matched primary tumors and metastases were more similar than of unrelated metastases/primary pairs, a result also reported in other organ systems, and that part of this similarity reflected patient background. We found that the comparison of patient-matched primary tumors and metastases was heavily confounded by the presence of lymphoid tissues in the metastasis samples. An original data adjustment procedure was developed to circumvent this problem. It revealed a differential expression of stroma-related gene expression signatures also regulated in other organ systems. The comparison of N0 vs. N+ primary tumors uncovered a signal irreproducible across independent PTC datasets. This signal was also detectable when comparing the normal thyroid tissues adjacent to N0 and N+ tumors, suggesting a cohort specific bias also likely to be present in previous studies with similar statistical power. Classification of N0 vs. N+ yielded an accuracy of 63%, but additional statistical controls not presented in previous studies, revealed that this is likely to occur by chance alone. To address this issue, we used large datasets from The Cancer Genome Atlas and showed that N0 vs. N+ classification rates could not be reached randomly for most cancers. Yet, it was significant, but of limited accuracy (<70%) for thyroid, breast and head and neck cancers. We profiled the transcriptomes of 11 primary PTCs with no detectable nodal invasion, 17 primary PTCs with nodal invasion and 17 patient-matched nodal metastases. We also profiled a number of control samples. These included 24 patient-matched normal thyroid tissues (11 from N0, 13 from N+ patients), and 4 normal lymph nodes; technical and biological replicates including additional nodal metastasis for 3 patients, adjacent blocks for 5 primary tumors, 4 normal thyroid tissues and 1 nodal metastasis.

Dataset Information

Integrative Proteogenomic Characterization Reveals Therapeutic Targets in Poorly Differentiated and Anaplastic Thyroid Cancers

Publications

Integrative proteogenomic characterization reveals therapeutic targets in poorly differentiated and anaplastic thyroid cancers.

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