Prospective observational study on biomarkers of response in pancreatic ductal adenocarcinoma

  • Nat Med. 2024 Jan 29. doi: 10.1038/s41591-023-02790-x.
Lingxi Jiang  #  1  2  3 ,  Jiejie Qin  #  1  2  3 ,  Yuting Dai  #  4 ,  Shulin Zhao  #  1  2  3 ,  Qian Zhan  #  1  2  3 ,  Peng Cui  #  5 ,  Lingjie Ren  1  2  3 ,  Xuelong Wang  1  2  3 ,  Ruihong Zhang  4 ,  Chenxu Gao  4 ,  Yanting Zhou  4 ,  Shangli Cai  5 ,  Guoqiang Wang  5 ,  Wenchuan Xie  5 ,  Xiaomei Tang  1  2  3 ,  Minmin Shi  1  2  3 ,  Fangfang Ma  1  2  3 ,  Jia Liu  1  2  3 ,  Ting Wang  6 ,  Chaofu Wang  6 ,  Magali Svrcek  7 ,  Armelle Bardier-Dupas  8 ,  Jean Francois Emile  9 ,  Louis de Mestier  10 ,  Jean-Baptiste Bachet  11 ,  Remy Nicolle  12 ,  Jerome Cros  13 ,  Pierre Laurent-Puig  14 ,  Miaoyan Wei  15 ,  Bin Song  16 ,  Wei Jing  16 ,  Shiwei Guo  16 ,  Kailian Zheng  16 ,  Hui Jiang  16  17 ,  Huan Wang  16 ,  Xiaxing Deng  1  2  3 ,  Hao Chen  1  2  3 ,  Qiang Tian  4 ,  Shengyue Wang  4 ,  Si Shi  18 ,  Gang Jin  19 ,  Tong Yin  20 ,  Hai Fang  21 ,  Saijuan Chen  22 ,  Baiyong Shen  23  24  25
Affiliations
  • 1. Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2. Research Institute of Pancreatic Diseases, Shanghai Key Laboratory of Translational Research for Pancreatic Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 3. State Key Laboratory of Systems Medicine for Cancer, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • 4. Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Centre for Translational Medicine at Shanghai, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 5. Burning Rock Biotech, Guangzhou, China.
  • 6. Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 7. Department of Pathology, Saint-Antoine Hospital - Sorbonne Universités, Paris, France.
  • 8. Department of Pathology, Pitié-Salpêtrière Hospital - Sorbonne Universités, Paris, France.
  • 9. Department of Pathology, Ambroise Paré Hospital - Université Saint Quentin en Yvelines, Paris, France.
  • 10. Department of Pancreatology, Université Paris Cité - FHU MOSAIC, Beaujon Hospital, Clichy, France.
  • 11. Department of Gastroenterology, Pitié-Salpêtrière Hospital - Sorbonne Universités, Paris, France.
  • 12. Université Paris Cité, FHU MOSAIC, Centre de Recherche sur l'Inflammation (CRI), INSERM, U1149, CNRS, ERL 8252, Paris, France.
  • 13. Department of Pathology, Université Paris Cité - FHU MOSAIC, Beaujon Hospital, Clichy, France.
  • 14. Department of Biochemistry, Hôpital Européen Georges Pompidou, Centre de Recherche des Cordeliers, INSERM UMRS1138, CNRS, Sorbonne Université, USPC, Université Paris Cité, Equipe labellisée Ligue Nationale contre le cancer, CNRS, Paris, France.
  • 15. Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
  • 16. Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, China.
  • 17. Department of Pathology, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, China.
  • 18. Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. [email protected].
  • 19. Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, China. [email protected].
  • 20. Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Centre for Translational Medicine at Shanghai, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
  • 21. Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Centre for Translational Medicine at Shanghai, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
  • 22. Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Centre for Translational Medicine at Shanghai, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
  • 23. Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
  • 24. Research Institute of Pancreatic Diseases, Shanghai Key Laboratory of Translational Research for Pancreatic Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
  • 25. State Key Laboratory of Systems Medicine for Cancer, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China. [email protected].
  • # Contributed equally.
PMID: 38287168 DOI: 10.1038/s41591-023-02790-x
Abstract

Adjuvant chemotherapy benefits patients with resected pancreatic ductal adenocarcinoma (PDAC), but the compromised physical state of post-operative patients can hinder compliance. Biomarkers that identify candidates for prompt Adjuvant therapy are needed. In this prospective observational study, 1,171 patients with PDAC who underwent pancreatectomy were enrolled and extensively followed-up. Proteomic profiling of 191 patient samples unveiled clinically relevant functional protein modules. A proteomics-level prognostic risk model was established for PDAC, with its utility further validated using a publicly available external cohort. More importantly, through an interaction effect regression analysis leveraging both clinical and proteomic datasets, we discovered two biomarkers (NDUFB8 and CEMIP2), indicative of the overall sensitivity of patients with PDAC to Adjuvant chemotherapy. The biomarkers were validated through immunohistochemistry on an internal cohort of 386 patients. Rigorous validation extended to two external multicentic cohorts-a French multicentric cohort (230 patients) and a cohort from two grade-A tertiary hospitals in China (466 patients)-enhancing the robustness and generalizability of our findings. Moreover, experimental validation through functional assays was conducted on PDAC cell lines and patient-derived organoids. In summary, our cohort-scale integration of clinical and proteomic data demonstrates the potential of proteomics-guided prognosis and biomarker-aided Adjuvant chemotherapy for PDAC.

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