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

doi:10.1038/s41421-022-00479-y

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 PuYuan 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^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal Article › peer-review

44 Citations (Scopus)

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.

Original language	English
Article number	120
Journal	Cell Discovery
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41421-022-00479-y
Publication status	Published - Dec 2022
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2022, The Author(s).

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@article{bb751078f7d54b2e961e813337a61227,

title = "Integrated proteogenomic characterization of medullary thyroid carcinoma",

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.",

author = "Xiao Shi and Yaoting Sun and Cenkai Shen and Yan Zhang and Rongliang Shi and Fan Zhang and Tian Liao and Guojun Lv and Zhengcai Zhu and Lianghe Jiao and Peng Li and Tiansheng Xu and Ning Qu and Naisi Huang and Jiaqian Hu and Tingting Zhang and Yanzi Gu and Guangqi Qin and Haixia Guan and Weilin Pu and Yuan Li and Xiang Geng and Yan Zhang and Tongzhen Chen and Shenglin Huang and Zhikang Zhang and Shuting Ge and Wu Wang and Weibo Xu and Pengcheng Yu and Zhongwu Lu and Yulong Wang and Liang Guo and Yu Wang and Tiannan Guo and Qinghai Ji and Wenjun Wei",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41421-022-00479-y",

language = "English",

volume = "8",

journal = "Cell Discovery",

issn = "2056-5968",

publisher = "Springer Nature",

number = "1",

}

Shi, X, Sun, Y, Shen, C, Zhang, Y, Shi, R, Zhang, F, Liao, T, Lv, G, Zhu, Z, Jiao, L, Li, P, Xu, T, Qu, N, Huang, N, Hu, J, Zhang, T, Gu, Y, Qin, G, Guan, H, Pu, W, Li, Y, Geng, X, Zhang, Y, Chen, T, Huang, S, Zhang, Z, Ge, S, Wang, W, Xu, W, Yu, P, Lu, Z, Wang, Y, Guo, L, Wang, Y, Guo, T, Ji, Q & Wei, W 2022, 'Integrated proteogenomic characterization of medullary thyroid carcinoma', Cell Discovery, vol. 8, no. 1, 120. https://doi.org/10.1038/s41421-022-00479-y

TY - JOUR

T1 - Integrated proteogenomic characterization of medullary thyroid carcinoma

AU - Shi, Xiao

AU - Sun, Yaoting

AU - Shen, Cenkai

AU - Zhang, Yan

AU - Shi, Rongliang

AU - Zhang, Fan

AU - Liao, Tian

AU - Lv, Guojun

AU - Zhu, Zhengcai

AU - Jiao, Lianghe

AU - Li, Peng

AU - Xu, Tiansheng

AU - Qu, Ning

AU - Huang, Naisi

AU - Hu, Jiaqian

AU - Zhang, Tingting

AU - Gu, Yanzi

AU - Qin, Guangqi

AU - Guan, Haixia

AU - Pu, Weilin

AU - Li, Yuan

AU - Geng, Xiang

AU - Zhang, Yan

AU - Chen, Tongzhen

AU - Huang, Shenglin

AU - Zhang, Zhikang

AU - Ge, Shuting

AU - Wang, Wu

AU - Xu, Weibo

AU - Yu, Pengcheng

AU - Lu, Zhongwu

AU - Wang, Yulong

AU - Guo, Liang

AU - Wang, Yu

AU - Guo, Tiannan

AU - Ji, Qinghai

AU - Wei, Wenjun

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

UR - https://www.webofscience.com/wos/woscc/full-record/WOS:000879781500002

UR - https://openalex.org/W4308388279

UR - https://www.scopus.com/pages/publications/85141495966

U2 - 10.1038/s41421-022-00479-y

DO - 10.1038/s41421-022-00479-y

M3 - Journal Article

SN - 2056-5968

VL - 8

JO - Cell Discovery

JF - Cell Discovery

IS - 1

M1 - 120

ER -

Integrated proteogenomic characterization of medullary thyroid carcinoma

Abstract

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