Insight of novel biomarkers for papillary thyroid carcinoma through multiomics

Wei Liu; Junkan Zhu; Zhen Wu; Yongxiang Yin; Qiao Wu; Yiming Wu; Jiaojiao Zheng; Cong Wang; Hongyan Chen; Talal Jamil Qazi; Jun Wu; Yuqing Zhang; Houbao Liu; Jingmin Yang; Daru Lu; Xumin Zhang; Zhilong Ai

doi:10.3389/fonc.2023.1269751

Insight of novel biomarkers for papillary thyroid carcinoma through multiomics

Front Oncol. 2023 Sep 19:13:1269751. doi: 10.3389/fonc.2023.1269751. eCollection 2023.

Authors

Wei Liu¹, Junkan Zhu^{1

2}, Zhen Wu³, Yongxiang Yin⁴, Qiao Wu^{1

3}, Yiming Wu⁵, Jiaojiao Zheng¹, Cong Wang^{1

6

7}, Hongyan Chen³, Talal Jamil Qazi⁸, Jun Wu⁹, Yuqing Zhang⁹, Houbao Liu¹⁰, Jingmin Yang^{3

5

11}, Daru Lu^{3

11}, Xumin Zhang³, Zhilong Ai¹

Affiliations

¹ Department of Surgery (Thyroid & Breast), Zhongshan Hospital, Fudan University, Shanghai, China.
² School of Basic Medical Sciences, Fudan University, Shanghai, China.
³ State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
⁴ Department of Pathology, Wuxi Maternal and Child Health Care Hospital, Womens Hospital of Jiangnan University, Jiangnan University, Jiangsu, China.
⁵ Shanghai WeHealth BioMedical Technology Co., Ltd., Shanghai, China.
⁶ Department of General Surgery, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China.
⁷ Xiamen Clinical Research Center for Cancer Therapy, Xiamen, China.
⁸ Department of Biomedical Engineering, Balochistan University of Engineering and Technology, Khuzdar, Pakistan.
⁹ Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Cell Bank, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
¹⁰ Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
¹¹ National Health Commission Key Laboratory of Birth Defects and Reproductive Health, Chongqing Population and Family Planning Science and Technology Research Institute, Chongqing, China.

Abstract

Introduction: The overdiagnosing of papillary thyroid carcinoma (PTC) in China necessitates the development of an evidence-based diagnosis and prognosis strategy in line with precision medicine. A landscape of PTC in Chinese cohorts is needed to provide comprehensiveness.

Methods: 6 paired PTC samples were employed for whole-exome sequencing, RNA sequencing, and data-dependent acquisition mass spectrum analysis. Weighted gene co-expression network analysis and protein-protein interactions networks were used to screen for hub genes. Moreover, we verified the hub genes' diagnostic and prognostic potential using online databases. Logistic regression was employed to construct a diagnostic model, and we evaluated its efficacy and specificity based on TCGA-THCA and GEO datasets.

Results: The basic multiomics landscape of PTC among local patients were drawn. The similarities and differences were compared between the Chinese cohort and TCGA-THCA cohorts, including the identification of PNPLA5 as a driver gene in addition to BRAF mutation. Besides, we found 572 differentially expressed genes and 79 differentially expressed proteins. Through integrative analysis, we identified 17 hub genes for prognosis and diagnosis of PTC. Four of these genes, ABR, AHNAK2, GPX1, and TPO, were used to construct a diagnostic model with high accuracy, explicitly targeting PTC (AUC=0.969/0.959 in training/test sets).

Discussion: Multiomics analysis of the Chinese cohort demonstrated significant distinctions compared to TCGA-THCA cohorts, highlighting the unique genetic characteristics of Chinese individuals with PTC. The novel biomarkers, holding potential for diagnosis and prognosis of PTC, were identified. Furthermore, these biomarkers provide a valuable tool for precise medicine, especially for immunotherapeutic or nanomedicine based cancer therapy.

Keywords: biomarkers; diagnosis; landscape; multiomics; papillary thyroid carcinoma; prediction; prognosis.

Grants and funding

This work was supported by the Shanghai Natural Science Foundation (No.21ZR1412000), high-level talent training project of Wuxi Taihu Talent Plan (No.BJ2020072), National Natural Science Foundation of China (No.32271495), China Postdoctoral Science Foundation (No.2022M720799), Key Clinical Specialty Discipline Construction Program of Fujian and the Clinical Medical Research Center Project of Xiamen City, and Medical and Health Guided Project of Xiamen (No.3502Z20224ZD1093).