Proteomics of adjacent-to-tumor samples uncovers clinically relevant biological events in hepatocellular carcinoma

Hongwen Zhu; Youpei Lin; Dayun Lu; Shisheng Wang; Yuejia Liu; Liangqing Dong; Qian Meng; Jing Gao; Yuqiu Wang; Nixue Song; Yuying Suo; Li Ding; Pei Wang; Bing Zhang; Daming Gao; Jia Fan; Qiang Gao; Hu Zhou

doi:10.1093/nsr/nwad167

Proteomics of adjacent-to-tumor samples uncovers clinically relevant biological events in hepatocellular carcinoma

Natl Sci Rev. 2023 Jun 2;10(8):nwad167. doi: 10.1093/nsr/nwad167. eCollection 2023 Aug.

Authors

Hongwen Zhu¹, Youpei Lin², Dayun Lu^{1

3}, Shisheng Wang⁴, Yuejia Liu³, Liangqing Dong², Qian Meng¹, Jing Gao¹, Yuqiu Wang¹, Nixue Song¹, Yuying Suo^{1

5}, Li Ding⁶, Pei Wang⁷, Bing Zhang⁸, Daming Gao^{5

9}, Jia Fan², Qiang Gao², Hu Zhou^{1

3

5}

Affiliations

¹ Department of Analytical Chemistry, State Key Laboratory of Drug Research and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
² Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China.
³ School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China.
⁴ Institutes for Systems Genetics and NHC Key Lab of Transplant Engineering and Immunology, Sichuan Provincial Engineering Laboratory of Pathology in Clinical Application, West China Hospital, Sichuan University, Chengdu 610041, China.
⁵ University of Chinese Academy of Sciences, Beijing 100049, China.
⁶ Department of Medicine, McDonnell Genome Institute, Siteman Cancer Center, Washington University, St. Louis, MI 63108, USA.
⁷ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, NewYork, NY 10029, USA.
⁸ Lester and Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
⁹ State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.

Abstract

Normal adjacent tissues (NATs) of hepatocellular carcinoma (HCC) differ from healthy liver tissues and their heterogeneity may contain biological information associated with disease occurrence and clinical outcome that has yet to be fully evaluated at the proteomic level. This study provides a detailed description of the heterogeneity of NATs and the differences between NATs and healthy livers and revealed that molecular features of tumor subgroups in HCC were partially reflected in their respective NATs. Proteomic data classified HCC NATs into two subtypes (Subtypes 1 and 2), and Subtype 2 was associated with poor prognosis and high-risk recurrence. The pathway and immune features of these two subtypes were characterized. Proteomic differences between the two NAT subtypes and healthy liver tissues were further investigated using data-independent acquisition mass spectrometry, revealing the early molecular alterations associated with the progression from healthy livers to NATs. This study provides a high-quality resource for HCC researchers and clinicians and may significantly expand the knowledge of tumor NATs to eventually benefit clinical practice.

Keywords: hepatocellular carcinoma; heterogeneity; normal tissue adjacent to tumor; proteomics.