Plasma proteome profiling reveals dynamic of cholesterol marker after dual blocker therapy

Jiacheng Lyu, Lin Bai, Yumiao Li, Xiaofang Wang, Zeya Xu, Tao Ji, Hua Yang, Zizheng Song, Zhiyu Wang, Yanhong Shang, Lili Ren, Yan Li, Aimin Zang, Youchao Jia () and Chen Ding ()
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Jiacheng Lyu: School of Life Sciences, Human Phenome Institute, Shanghai Pudong Hospital, Fudan University
Lin Bai: School of Life Sciences, Human Phenome Institute, Shanghai Pudong Hospital, Fudan University
Yumiao Li: Affiliated Hospital of Hebei University; Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy
Xiaofang Wang: Affiliated Hospital of Hebei University; Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy
Zeya Xu: School of Life Sciences, Human Phenome Institute, Shanghai Pudong Hospital, Fudan University
Tao Ji: School of Life Sciences, Human Phenome Institute, Shanghai Pudong Hospital, Fudan University
Hua Yang: Affiliated Hospital of Hebei University; Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy
Zizheng Song: Affiliated Hospital of Hebei University; Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy
Zhiyu Wang: Affiliated Hospital of Hebei University; Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy
Yanhong Shang: Affiliated Hospital of Hebei University; Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy
Lili Ren: Affiliated Hospital of Hebei University; Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy
Yan Li: Hebei General Hospital
Aimin Zang: Affiliated Hospital of Hebei University; Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy
Youchao Jia: Affiliated Hospital of Hebei University; Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy
Chen Ding: School of Life Sciences, Human Phenome Institute, Shanghai Pudong Hospital, Fudan University

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Dual blocker therapy (DBT) has the enhanced antitumor benefits than the monotherapy. Yet, few effective biomarkers are developed to monitor the therapy response. Herein, we investigate the DBT longitudinal plasma proteome profiling including 113 longitudinal samples from 22 patients who received anti-PD1 and anti-CTLA4 DBT therapy. The results show the immune response and cholesterol metabolism are upregulated after the first DBT cycle. Notably, the cholesterol metabolism is activated in the disease non-progressive group (DNP) during the therapy. Correspondingly, the clinical indicator prealbumin (PA), free triiodothyronine (FT3) and triiodothyronine (T3) show significantly positive association with the cholesterol metabolism. Furthermore, by integrating proteome and radiology approach, we observe the high-density lipoprotein partial remodeling are activated in DNP group and identify a candidate biomarker APOC3 that can reflect DBT response. Above, we establish a machine learning model to predict the DBT response and the model performance is validated by an independent cohort with balanced accuracy is 0.96. Thus, the plasma proteome profiling strategy evaluates the alteration of cholesterol metabolism and identifies a panel of biomarkers in DBT.

Date: 2024
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DOI: 10.1038/s41467-024-47835-y

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