학술논문

Prospective observational study on biomarkers of response in pancreatic ductal adenocarcinoma.
Document Type
Academic Journal
Author
Jiang L; Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Research Institute of Pancreatic Diseases, Shanghai Key Laboratory of Translational Research for Pancreatic Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; State Key Laboratory of Systems Medicine for Cancer, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.; Qin J; Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Research Institute of Pancreatic Diseases, Shanghai Key Laboratory of Translational Research for Pancreatic Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; State Key Laboratory of Systems Medicine for Cancer, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.; Dai Y; 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.; Zhao S; Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Research Institute of Pancreatic Diseases, Shanghai Key Laboratory of Translational Research for Pancreatic Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; State Key Laboratory of Systems Medicine for Cancer, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.; Zhan Q; Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Research Institute of Pancreatic Diseases, Shanghai Key Laboratory of Translational Research for Pancreatic Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; State Key Laboratory of Systems Medicine for Cancer, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.; Cui P; Burning Rock Biotech, Guangzhou, China.; Ren L; Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Research Institute of Pancreatic Diseases, Shanghai Key Laboratory of Translational Research for Pancreatic Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; State Key Laboratory of Systems Medicine for Cancer, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.; Wang X; Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Research Institute of Pancreatic Diseases, Shanghai Key Laboratory of Translational Research for Pancreatic Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; State Key Laboratory of Systems Medicine for Cancer, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.; Zhang R; 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.; Gao C; 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.; Zhou Y; 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.; Cai S; Burning Rock Biotech, Guangzhou, China.; Wang G; Burning Rock Biotech, Guangzhou, China.; Xie W; Burning Rock Biotech, Guangzhou, China.; Tang X; Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Research Institute of Pancreatic Diseases, Shanghai Key Laboratory of Translational Research for Pancreatic Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; State Key Laboratory of Systems Medicine for Cancer, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.; Shi M; Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Research Institute of Pancreatic Diseases, Shanghai Key Laboratory of Translational Research for Pancreatic Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; State Key Laboratory of Systems Medicine for Cancer, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.; Ma F; Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Research Institute of Pancreatic Diseases, Shanghai Key Laboratory of Translational Research for Pancreatic Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; State Key Laboratory of Systems Medicine for Cancer, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.; Liu J; Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Research Institute of Pancreatic Diseases, Shanghai Key Laboratory of Translational Research for Pancreatic Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; State Key Laboratory of Systems Medicine for Cancer, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.; Wang T; Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Wang C; Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Svrcek M; Department of Pathology, Saint-Antoine Hospital - Sorbonne Universités, Paris, France.; Bardier-Dupas A; Department of Pathology, Pitié-Salpêtrière Hospital - Sorbonne Universités, Paris, France.; Emile JF; Department of Pathology, Ambroise Paré Hospital - Université Saint Quentin en Yvelines, Paris, France.; de Mestier L; Department of Pancreatology, Université Paris Cité - FHU MOSAIC, Beaujon Hospital, Clichy, France.; Bachet JB; Department of Gastroenterology, Pitié-Salpêtrière Hospital - Sorbonne Universités, Paris, France.; Nicolle R; Université Paris Cité, FHU MOSAIC, Centre de Recherche sur l'Inflammation (CRI), INSERM, U1149, CNRS, ERL 8252, Paris, France.; Cros J; Department of Pathology, Université Paris Cité - FHU MOSAIC, Beaujon Hospital, Clichy, France.; Laurent-Puig P; 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.; Wei M; Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.; Song B; Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, China.; Jing W; Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, China.; Guo S; Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, China.; Zheng K; Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, China.; Jiang H; Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, China.; Department of Pathology, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, China.; Wang H; Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, China.; Deng X; Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Research Institute of Pancreatic Diseases, Shanghai Key Laboratory of Translational Research for Pancreatic Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; State Key Laboratory of Systems Medicine for Cancer, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.; Chen H; Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Research Institute of Pancreatic Diseases, Shanghai Key Laboratory of Translational Research for Pancreatic Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; State Key Laboratory of Systems Medicine for Cancer, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.; Tian Q; 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.; Wang S; 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.; Shi S; Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. shisi@fudanpci.org.; Jin G; Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, China. jingang@smmu.edu.cn.; Yin T; 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. yintong0101@163.com.; Fang H; 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. fh12355@rjh.com.cn.; Chen S; 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. sjchen@stn.sh.cn.; Shen B; Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. shenby@shsmu.edu.cn.; Research Institute of Pancreatic Diseases, Shanghai Key Laboratory of Translational Research for Pancreatic Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, China. shenby@shsmu.edu.cn.; State Key Laboratory of Systems Medicine for Cancer, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China. shenby@shsmu.edu.cn.
Source
Publisher: Nature Publishing Company Country of Publication: United States NLM ID: 9502015 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-170X (Electronic) Linking ISSN: 10788956 NLM ISO Abbreviation: Nat Med Subsets: MEDLINE
Subject
Language
English
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.
(© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)