Comprehensive proteome, phosphoproteome and kinome characterization of luminal A breast cancer

Ganglong Yang; Chenyang Zuo; Yuxiang Lin; Xiaoman Zhou; Piaopiao Wen; Chairui Zhang; Han Xiao; Meichen Jiang; Morihisa Fujita; Xiao-Dong Gao; Fangmeng Fu

doi:10.3389/fonc.2023.1127446

Comprehensive proteome, phosphoproteome and kinome characterization of luminal A breast cancer

Front Oncol. 2023 Mar 31:13:1127446. doi: 10.3389/fonc.2023.1127446. eCollection 2023.

Authors

Ganglong Yang^{1

2}, Chenyang Zuo², Yuxiang Lin^{3

4

5}, Xiaoman Zhou², Piaopiao Wen², Chairui Zhang², Han Xiao⁶, Meichen Jiang⁶, Morihisa Fujita², Xiao-Dong Gao¹, Fangmeng Fu^{3

4

5}

Affiliations

¹ The Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, China.
² State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China.
³ Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
⁴ Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
⁵ Breast Cancer Institute, Fujian Medical University, Fuzhou, Fujian, China.
⁶ Department of Pathology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.

Abstract

Background: Breast cancer is one of the most frequently occurring malignant cancers worldwide. Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the two most common histological subtypes of breast cancer. In this study, we aimed to deeply explore molecular characteristics and the relationship between IDC and ILC subtypes in luminal A subgroup of breast cancer using comprehensive proteomics and phosphoproteomics analysis.

Methods: Cancer tissues and noncancerous adjacent tissues (NATs) with the luminal A subtype (ER- and PR-positive, HER2-negative) were obtained from paired IDC and ILC patients respectively. Label-free quantitative proteomics and phosphoproteomics methods were used to detect differential proteins and the phosphorylation status between 10 paired breast cancer and NATs. Then, the difference in protein expression and its phosphorylation between IDC and ILC subtypes were explored. Meanwhile, the activation of kinases and their substrates was also revealed by Kinase-Substrate Enrichment Analysis (KSEA).

Results: In the luminal A breast cancer, a total of 5,044 high-confidence proteins and 3,808 phosphoproteins were identified from 10 paired tissues. The protein phosphorylation level in ILC tissues was higher than that in IDC tissues. Histone H1.10 was significantly increased in IDC but decreased in ILC, Conversely, complement C4-B and Crk-like protein were significantly decreased in IDC but increased in ILC. Moreover, the increased protein expression of Septin-2, Septin-9, Heterogeneous nuclear ribonucleoprotein A1 and Kinectin but reduce of their phosphorylation could clearly distinguish IDC from ILC. In addition, IDC was primarily related to energy metabolism and MAPK pathway, while ILC was more closely involved in the AMPK and p53/p21 pathways. Furthermore, the kinomes in IDC were primarily significantly activated in the CMGC groups.

Conclusions: Our research provides insights into the molecular characterization of IDC and ILC and contributes to discovering novel targets for further drug development and targeted treatment.

Keywords: invasive ductal carcinoma (IDC); invasive lobular carcinoma (ILC); kinome; luminal A breast cancer; phosphoproteome; proteome.

Grants and funding

This work was supported by grants from the Program of Introducing Talents of Discipline to Universities (No. 111-2-06), National Natural Science Foundation of China (No. 21778023), Top-notch Academic Programs Project of Jiangsu Higher Education Institutions, and Natural Science Foundation of Fujian Province (No. 2021J01737) and Shandong Provincial Major Scientific and Technological Innovation Project (No. 2019JZZY011006). We thank Wenyan Chen from School of Biotechnology ,Jiangnan University for her contribution in the sample processing.