Cell Discovery (Nov 2022)
Integrated proteogenomic characterization of medullary thyroid carcinoma
- Xiao Shi,
- Yaoting Sun,
- Cenkai Shen,
- Yan Zhang,
- Rongliang Shi,
- Fan Zhang,
- Tian Liao,
- Guojun Lv,
- Zhengcai Zhu,
- Lianghe Jiao,
- Peng Li,
- Tiansheng Xu,
- Ning Qu,
- Naisi Huang,
- Jiaqian Hu,
- Tingting Zhang,
- Yanzi Gu,
- Guangqi Qin,
- Haixia Guan,
- Weilin Pu,
- Yuan Li,
- Xiang Geng,
- Yan Zhang,
- Tongzhen Chen,
- Shenglin Huang,
- Zhikang Zhang,
- Shuting Ge,
- Wu Wang,
- Weibo Xu,
- Pengcheng Yu,
- Zhongwu Lu,
- Yulong Wang,
- Liang Guo,
- Yu Wang,
- Tiannan Guo,
- Qinghai Ji,
- Wenjun Wei
Affiliations
- Xiao Shi
- Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
- Yaoting Sun
- Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study; Research Center for Industries of the Future, Westlake University, Hangzhou
- Cenkai Shen
- Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
- Yan Zhang
- Department of Head and Neck Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou
- Rongliang Shi
- Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
- Fan Zhang
- Shanghai OE Biotech Co., Ltd
- Tian Liao
- Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
- Guojun Lv
- Department of General Surgery, Changzhou Second People’s Hospital
- Zhengcai Zhu
- Department of Thyroid and Breast Surgery, Taizhou People’s Hospital
- Lianghe Jiao
- Department of Thyroid and Breast Surgery, Taizhou People’s Hospital
- Peng Li
- Department of Thyroid and Parathyroid Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Centre, Shenzhen
- Tiansheng Xu
- Shanghai OE Biotech Co., Ltd
- Ning Qu
- Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
- Naisi Huang
- Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
- Jiaqian Hu
- Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
- Tingting Zhang
- Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
- Yanzi Gu
- Biobank, Fudan University Shanghai Cancer Center
- Guangqi Qin
- Biobank, Fudan University Shanghai Cancer Center
- Haixia Guan
- Department of Endocrinology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences; The Second School of Clinical Medicine, Southern Medical University, Guangzhou
- Weilin Pu
- State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences; Human Phenome Institute, Fudan University
- Yuan Li
- Department of General Surgery, Changzhou Second People’s Hospital
- Xiang Geng
- Department of General Surgery, Changzhou Second People’s Hospital
- Yan Zhang
- Department of Pathology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
- Tongzhen Chen
- Department of Pathology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
- Shenglin Huang
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center; Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University
- Zhikang Zhang
- Shanghai OE Biotech Co., Ltd
- Shuting Ge
- Shanghai Luming Biological Technology Co., Ltd.
- Wu Wang
- Shanghai OE Biotech Co., Ltd
- Weibo Xu
- Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
- Pengcheng Yu
- Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
- Zhongwu Lu
- Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
- Yulong Wang
- Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
- Liang Guo
- Department of Head and Neck Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou
- Yu Wang
- Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
- Tiannan Guo
- Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study; Research Center for Industries of the Future, Westlake University, Hangzhou
- Qinghai Ji
- Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
- Wenjun Wei
- Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University
- DOI
- https://doi.org/10.1038/s41421-022-00479-y
- Journal volume & issue
-
Vol. 8,
no. 1
pp. 1 – 22
Abstract
Abstract Medullary thyroid carcinoma (MTC) is a rare neuroendocrine malignancy derived from parafollicular cells (C cells) of the thyroid. Here we presented a comprehensive multi-omics landscape of 102 MTCs through whole-exome sequencing, RNA sequencing, DNA methylation array, proteomic and phosphoproteomic profiling. Integrated analyses identified BRAF and NF1 as novel driver genes in addition to the well-characterized RET and RAS proto-oncogenes. Proteome-based stratification of MTCs revealed three molecularly heterogeneous subtypes named as: (1) Metabolic, (2) Basal and (3) Mesenchymal, which are distinct in genetic drivers, epigenetic modification profiles, clinicopathologic factors and clinical outcomes. Furthermore, we explored putative therapeutic targets of each proteomic subtype, and found that two tenascin family members TNC/TNXB might serve as potential prognostic biomarkers for MTC. Collectively, our study expands the knowledge of MTC biology and therapeutic vulnerabilities, which may serve as an important resource for future investigation on this malignancy.
