Jonghwa Jin1, Minsoo Son1, Hyeyoon Kim2, Hyeyeon Kim2, Seong-Ho Kong3, Hark Kyun Kim4, Youngsoo Kim5, Dohyun Han6. 1. Department of Biomedical Engineering, Seoul National University College of Medicine, 28 Yongon-Dong, Jongno-gu, Seoul, Republic of Korea; Institute of Medical & Biological Engineering, Seoul National University College of Medicine, 28 Yongon-Dong, Jongno-gu, Seoul, Republic of Korea. 2. Proteomics core facility, Biomedical Research Institute, Seoul National University Hospital, 71 Daehak-ro, Jongno-gu, Seoul, Republic of Korea. 3. Department of Surgery, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, Republic of Korea. 4. Biomolecular Function Research Branch, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, Republic of Korea. 5. Department of Biomedical Engineering, Seoul National University College of Medicine, 28 Yongon-Dong, Jongno-gu, Seoul, Republic of Korea; Institute of Medical & Biological Engineering, Seoul National University College of Medicine, 28 Yongon-Dong, Jongno-gu, Seoul, Republic of Korea. Electronic address: biolab@snu.ac.kr. 6. Department of Biomedical Engineering, Seoul National University College of Medicine, 28 Yongon-Dong, Jongno-gu, Seoul, Republic of Korea; Institute of Medical & Biological Engineering, Seoul National University College of Medicine, 28 Yongon-Dong, Jongno-gu, Seoul, Republic of Korea; Proteomics core facility, Biomedical Research Institute, Seoul National University Hospital, 71 Daehak-ro, Jongno-gu, Seoul, Republic of Korea. Electronic address: hdh03@snu.ac.kr.
Abstract
OBJECTIVES: Malignant ascites is a sign of peritoneal seeding, which is one of the most frequent forms of incurable distant metastasis. Because the development of malignant ascites is associated with an extremely poor prognosis, determining whether it resulted from peritoneal seeding has critical clinical implications in diagnosis, choice of treatment, and active surveillance. At present, the molecular characterizations of malignant ascites are especially limited in case of gastric cancer. We aimed to identify malignant ascites-specific proteins that may contribute to the development of alternative methods for diagnosis and therapeutic monitoring and also increase our understanding of the pathophysiology of peritoneal seeding. DESIGN & METHODS: First, comprehensive proteomic strategies were employed to construct an in-depth proteome of ascitic fluids. Label-free quantitative proteomic analysis was subsequently performed to identify candidates that can differentiate between malignant ascitic fluilds of gastric cancer patients from benign ascitic fluids. Finally, two candidate proteins were verified by ELISA in 84 samples with gastric cancer or liver cirrhosis. RESULTS: Comprehensive proteome profiling resulted in the identification of 5347 ascites proteins. Using label-free quantification, we identified 299 proteins that were differentially expressed in ascitic fluids between liver cirrhosis and stage IV gastric cancer patients. In addition, we identified 645 proteins that were significantly expressed in ascitic fluids between liver cirrhosis and gastric cancer patients with peritoneal seeding. Finally, Gastriscin and Periostin that can distinguish malignant ascites from benign ascites were verified by ELISA. CONCLUSIONS: This study identified and verified protein markers that can distinguish malignant ascites with or without peritoneal seeding from benign ascites. Consequently, our results could be a significant resource for gastric cancer research and biomarker discovery in the diagnosis of malignant ascites.
OBJECTIVES:Malignant ascites is a sign of peritoneal seeding, which is one of the most frequent forms of incurable distant metastasis. Because the development of malignant ascites is associated with an extremely poor prognosis, determining whether it resulted from peritoneal seeding has critical clinical implications in diagnosis, choice of treatment, and active surveillance. At present, the molecular characterizations of malignant ascites are especially limited in case of gastric cancer. We aimed to identify malignant ascites-specific proteins that may contribute to the development of alternative methods for diagnosis and therapeutic monitoring and also increase our understanding of the pathophysiology of peritoneal seeding. DESIGN & METHODS: First, comprehensive proteomic strategies were employed to construct an in-depth proteome of ascitic fluids. Label-free quantitative proteomic analysis was subsequently performed to identify candidates that can differentiate between malignant ascitic fluilds of gastric cancerpatients from benign ascitic fluids. Finally, two candidate proteins were verified by ELISA in 84 samples with gastric cancer or liver cirrhosis. RESULTS: Comprehensive proteome profiling resulted in the identification of 5347 ascites proteins. Using label-free quantification, we identified 299 proteins that were differentially expressed in ascitic fluids between liver cirrhosis and stage IV gastric cancerpatients. In addition, we identified 645 proteins that were significantly expressed in ascitic fluids between liver cirrhosis and gastric cancerpatients with peritoneal seeding. Finally, Gastriscin and Periostin that can distinguish malignant ascites from benign ascites were verified by ELISA. CONCLUSIONS: This study identified and verified protein markers that can distinguish malignant ascites with or without peritoneal seeding from benign ascites. Consequently, our results could be a significant resource for gastric cancer research and biomarker discovery in the diagnosis of malignant ascites.
Authors: Josephine Hendrikson; Ying Liu; Wai Har Ng; Jing Yi Lee; Abner Herbert Lim; Jui Wan Loh; Cedric C Y Ng; Whee Sze Ong; Joey Wee-Shan Tan; Qiu Xuan Tan; Gillian Ng; Nicholas B Shannon; Weng Khong Lim; Tony K H Lim; Clarinda Chua; Jolene Si Min Wong; Grace Hwei Ching Tan; Jimmy Bok Yan So; Khay Guan Yeoh; Bin Tean Teh; Claramae Shulyn Chia; Khee Chee Soo; Oi Lian Kon; Iain Beehuat Tan; Jason Yongsheng Chan; Melissa Ching Ching Teo; Chin-Ann J Ong Journal: Cell Rep Med Date: 2022-02-15