Overview

Laboratory Introduction

Laboratory of Gastric Cancer Biology

Laboratory of Gastric Cancer Biology
The Gastric Cancer Biology Laboratory was established for the study of the development, diagnosis, and treatment of gastric cancer. In 1998, after completing a fellowship at the NCI and NIH, Professor Han-Kwang Yang returned to Seoul National University to lead gastric cancer research at the Cancer Research Center (CRC). Through an interdisciplinary cancer biology research program, the CRC actively trains graduate students to become the next generation of innovators in cancer research. Under the leadership of Professors Han-Kwang Yang, Hyuk-Joon Lee, Do Joong Park, Seong-Ho Kong, and Yun-Suhk Suh, of the Department of Gastrointestinal Surgery at Seoul National University Hospital, the Gastric Cancer Biology Lab conducts extensive basic, translational, and clinical research with the collective effort of graduate students, clinical instructors, specialists, and research nurses. The lab is also further involved in collaborations with several national and international institutions.
Related Researcher
양한광

Han-Kwang Yang Professor

이혁준

Hyuk-Joon Lee Professor

박도중

Do Joong Park Professor

Research topics

The Gastric Cancer Biology Laboratory in the Department of Gastrointestinal Surgery uses clinical data collected from over 700 cases of gastric cancer each year—totaling 30,000 cases as of 2019—as well as gastric cancer tissue acquired from over 1,800 patients to conduct research in the diagnosis and treatment of the disease. Current research topics include cancer-specific imaging, genomics, biomarker discovery, immunotherapeutic study, and 3D modeling. Joint research efforts are also ongoing with various organizations across South Korea, the United States, China, Japan, and Europe. Through experiments using in vitro and in vivo models, we are working to develop new diagnostic and treatment techniques for the advancement of gastric cancer care.
 
(1) Study on the mechanism of development and metastasis of gastric cancer
-Genome research related to the development, staging, and after effects of gastric cancer
-Epigenetic studies such as microRNA and DNA methylation related to gastric cancer
-Mechanistic studies on the development of gastric cancer, including the significance of SPEM (spasmolytic-polypeptide expressing metaplasia), utilizing animal experiments and patient-derived cancer tissue studies
-Angiogenesis studies (neo-angiogenesis)
 
(2) Development of diagnostic technology
-Development of non-invasive technology to diagnose gastric cancer patients using exhaled breath and feces
-Identification of genomic and protein markers that can be used for the early diagnosis, recurrence, and prognosis prediction utilizing the blood and tissue of gastric cancer patients
 
(3) Gastric cancer treatment study
-Research related to cancer cell contamination during gastric cancer surgery (eg, research evaluating and developing surgical instruments/techniques regarding intraperitoneal release of cancer cells that can cause peritoneal dissemination)
-Stomach cancer-specific imaging of gastric cancer cell binding capacity and fluorescence expression level of gastric cancer markers in small animal models based on near-infrared molecular imaging techniques. These techniques would further be utilized for personalized gastric cancer surgery (eg. Image-guided surgery) and diagnostic strategies (eg. Near-infrared endoscopy)
- Development of gastrointestinal stromal tumors (GISTs)-specific immune probes targeting overexpressed GIST markers in patients. These probes would further be utilized for visual biopsy of GIST samples and image-guided surgery.
- Testing the anticancer effects of immune checkpoint inhibitors and novel immunotherapeutic agents specific for gastric cancer by evaluating various immune cells (eg. T cells, NK cells, Tregs, bone marrow-derived suppressor cells (MDSCs), dendritic cells, M1/M2 macrophages) and the tumor microenvironment (TME) through gastric cancer mouse models. These studies would be used to identify and establish a treatment protocol to achieve optimal drug efficacy.
 
(4) Genomics research and patient-derived xenograft model using high throughput omics technologies for gastric cancer
-cDNA microarray and next generation sequencing (NGS) research to discover markers related to lymph node metastasis and therapeutic targets
-Construction of a patient-derived xenograft (PDX) model in which gastric cancer tissues are transplanted into immunodeficient mice. Using this model, analyses of genomes related to various phenotypes of gastric cancer are conducted to determine diagnostic markers and test patient reactivity to various anticancer drug combinations. These models can also be used as major experimental assets for other research, including imaging studies for biomarker discovery.
-Studies on the gut microbiome of gastric cancer patients
 
(5) Surgical treatment, simulation, and prediction research using 3D reconstruction and analysis of medical images
-3D modeling and reconstruction and CT volumetry analysis using volume rendering software (Mimics, Medip, DeepCatch, Meshmixer, etc.)
-Prediction of volume change after gastrectomy using 3D modeling software. Digital model of stomach organs and blood vessels for surgical practice. 3D printing models of the oral cavity, esophagus and stomach for the practice of endoscopic techniques
-Comparative analysis of body composition of pre- and post-operative muscle, abdominal visceral fat, and subcutaneous fat of a patient who underwent gastric cancer surgery to predict future quality of life.
 
(6) Development of surgical instruments and robotic systems
-Collaboration of 3D printing and robot researchers to develop surgical instruments and robotic surgical systems, which can be used to verify surgical models (eg. large animal models).

Research goals

By utilizing abundant research resources and platforms such as gastric cancer patient tissues, patient-derived mouse models, and genomic data accumulated through next-generation sequencing analysis, we can further elucidate the mechanism of gastric cancer occurrence and progression, and through various approaches to cancer treatment, find ways to increase the effectiveness of treatment. By answering scientific questions raised by gastric cancer treatment, including surgery, and leading the development of early diagnosis and patient-specific therapeutic methods, we also continuously strive to ensure a healthy life for our patients not only through treatment but also focusing on their quality of life afterwards. In addition to collaboration with renowned domestic and foreign institutions and research teams, we are actively conducting basic, clinical, and translational research within the gastric cancer biology laboratory to further advance the treatment of gastric cancer, the most prevalent cancer in Korea, and to look after the satisfaction and happiness of our patients.

Research achievements
-Woo XY, Giordano J, Srivastava A, Zhao ZM, Lloyd MW, de Bruijn R, Suh YS, Patidar R, Chen L, Scherer S, Bailey MH, Yang CH, Cortes-Sanchez E, Xi Y, Wang J, Wickramasinghe J, Kossenkov AV, Rebecca VW, Sun H, Mashl RJ, Davies SR, Jeon R, Frech C, Randjelovic J, Rosains J, Galimi F, Bertotti A, Lafferty A, O'Farrell AC, Modave E, Lambrechts D, Ter Brugge P, Serra V, Marangoni E, El Botty R, Kim H, Kim JI, Yang HK, Lee C, Dean DA 2nd, Davis-Dusenbery B, Evrard YA, Doroshow JH, Welm AL, Welm BE, Lewis MT, Fang B, Roth JA, Meric-Bernstam F, Herlyn M, Davies MA, Ding L, Li S, Govindan R, Isella C, Moscow JA, Trusolino L, Byrne AT, Jonkers J, Bult CJ, Medico E, Chuang JH; PDXNET Consortium; EurOPDX Consortium. Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts. Nat Genet. 2021 Jan;53(1):86-99.
- Ashoka AH, Kong SH, Seeliger B, Andreiuk B, Soares RV, Barberio M, Diana M, Klymchenko AS. Near-infrared fluorescent coatings of medical devices for image-guided surgery. Biomaterials. 2020 Dec;261:120306.
-Berlth F, Kim WH, Choi JH, Park SH, Kong SH, Lee HJ, Yang HK. Prognostic Impact of Frozen Section Investigation and Extent of Proximal Safety Margin in Gastric Cancer Resection. Ann Surg. 2020 Nov;272(5):871-878.
-Suh YS, Na D, Lee JS, Chae J, Kim E, Jang G, Lee J, Min J, Ock CY, Kong SH, George J, Zhang C, Lee HJ, Kim JI, Kim SJ, Kim WH, Lee C, Yang HK. Comprehensive Molecular Characterization of Adenocarcinoma of the Gastroesophageal Junction Between Esophageal and Gastric Adenocarcinomas. Ann Surg. 2020 Oct 19. [Online ahead of print]
-Peille AL, Vuaroqueaux V, Wong SS, Ting J, Klingner K, Zeitouni B, Landesfeind M, Kim WH, Lee HJ, Kong SH, Wulur I, Bray S, Bronsert P, Zanella N, Donoho G, Yang HK, Fiebig HH, Reinhard C, Aggarwal A. Evaluation of molecular subtypes and clonal selection during establishment of patient-derived tumor xenografts from gastric adenocarcinoma. Commun Biol. 2020 Jul 9;3(1):367.
-Lee SH, Jang DK, Yoo MW, -Hwang SH, Ryu SY, Kwon OK, Hur H, Man Yoon H, Eom BW, Ahn HS, Son T, Song KY, Lee HH, Choi MG, An JY, Lee SI, Lee KH, Ahn S, Park YS, Park DJ; Efficacy and Safety of DWJ1319 in the Prevention of Gallstone Formation after Gastrectomy in Patient with Gastric Cancer: A Multicenter, Randomized, Double-blind, Placebo-controlled Study (PEGASUS-D) Group. Efficacy and Safety of Ursodeoxycholic Acid for the Prevention of Gallstone Formation After Gastrectomy in Patients With Gastric Cancer: The PEGASUS-D Randomized Clinical Trial. JAMA Surg. 2020 Jun 17;155(8):703–11.
-Min JM, Han TS, Sohn YJ, Takahiro Shimizu, Choi BR, Bae SW, Hur K, Kong SH, Suh YS, Lee HJ, Kim JS, Min JK, Kim WH, Kim VN, Choi EY, James R.Goldenring, Yang HK. microRNA-30a arbitrates intestinal-type early gastriccarcinogenesis by directly targeting ITGA2. Gastric Cancer. 2020 Jul;23(4):600-613.
-Bae SW, Felix Berlth, Jeong KY, Suh YS, Kong SH, Lee HJ, Kim WH, Chung JK, Yang HK. Establishment of a [18F]-FDG-PET/MRI Imaging Protocol for Gastric Cancer PDX as a Preclinical Research Tool. J Gastric Cancer. 2020 Mar; 20(1): 60–71.
-Kanda M, Suh YS, Park DJ, Tanaka C, Ahn SH, Kong SH, Lee HJ, Kobayashi D, Fujiwara M, Shimada H, Cho B, Murotani K, Kim HH, Yang HK, Kodera Y. Serum levels of ANOS1 serve as a diagnostic biomarker of gastric cancer: a prospective multicenter observational study. Gastric Cancer. 2020 Mar;23(2):203-211.
-Han TS, Voon DC, Oshima H, Nakayama M, Echizen K, Sakai E, Yong ZWE, Murakami K, Yu L, Minamoto T, Ock CY, Jenkins BJ, Kim SJ, Yang HK, Oshima M. Interleukin 1 Up-regulates MicroRNA 135b to Promote Inflammation-Associated Gastric Carcinogenesis in Mice. Gastroenterology. 2019 Mar;156(4):1140-1155.e4.
- Lee HJ, Hyung WJ, Yang HK, Han SU, Park YK, An JY, Kim W, Kim HI, Kim HH, Ryu SW, Hur H, Kong SH, Cho GS, Kim JJ, Park DJ, Ryu KW, Kim YW, Kim JW, Lee JH, Kim MC; Korean Laparo-endoscopic Gastrointestinal Surgery Study (KLASS) Group. Short-term Outcomes of a Multicenter Randomized Controlled Trial Comparing Laparoscopic Distal Gastrectomy With D2 Lymphadenectomy to Open Distal Gastrectomy for Locally Advanced Gastric Cancer (KLASS-02-RCT). Ann Surg. 2019 Dec;270(6):983-991
- Anderson BW, Suh YS, Choi B, Lee HJ, Yab TC, Taylor W, Dukek BA, Berger CK, Cao X, Foote PH, Devens ME, Boardman LA, Kisiel JB, Mahoney DW, Slettedahl SW, Allawi HT, Lidgard GP, Smyrk TC, Yang HK, Ahlquist DA. Detection of Gastric Cancer with Novel Methylated DNA Markers: Discovery, Tissue Validation, and Pilot Testing in Plasma. Clin Cancer Res 2018 Nov 15;24(22):5724-5734.
- Kong SH, Kim SM, Kim DG, Park KH, Suh YS, Kim TH, Kim IJ, Seo JH, Lim YJ, Lee HJ, Yang HK. Intraoperative Neurophysiologic Testing of the Perigastric Vagus Nerve Branches to Evaluate Viability and Signals along Nerve Pathways during Gastrectomy. J Gastric Cancer. 2019 Mar;19(1):49-61.
-Huh YJ, Son YG, Kim TH, Park JH, Oh TJ, Choi B, Min J, Cho YM, Yang HK, Lee HJ. Effect and Mechanisms of Diabetes Resolution According to the Range of Gastric Resection and the Length of Anastomosis in Animal Models: Implication for Gastric Cancer Surgery in Patients with Diabetes Mellitus. World J Surg. 2018 Apr;42(4):1056-1064.
-Cho SY, Sung CO, Chae J, Lee J, Na D, Kang W, Kang J, Min S, Lee A, Kwak E, Kim J, Choi B, Kim H, Chuang JH, Pak HK, Park CS, Park S, Ko YH, Lee D, Roh J, Cho MS, Park S, Ju YS, Suh YS, Kong SH, Lee HJ, Keck J, Banchereau J, Liu ET, Kim WH, Park H, Yang HK, Kim JI, Lee C. Alterations in the Rho pathway contribute to Epstein-Barr virus-induced lymphomagenesis in immunosuppressed environments. Blood. 2018 Apr 26;131(17):1931-1941.
-Choi B, Lee HJ, Min J, Choe HN, Choi YS, Son YG, Ahn HS, Suh YS, Goldenring JR, Yang HK. Plasma expression of the intestinal metaplasia markers CDH17 and TFF3 in patients with gastric cancer. Cancer Biomark. 2017 Jul 4;19(3):231-239.
-Min J, Choi B, Han TS, Lee HJ, Kong SH, Suh YS, Kim TH, Choe HN, Kim WH, Hur K, Yang HK. Methylation Levels of LINE-1 As a Useful Marker for Venous Invasion in Both FFPE and Frozen Tumor Tissues of Gastric Cancer. Mol Cells. 2017 May 31;40(5):346-354.
-Choi B, Yu J, Han TS, Kim YK, Hur K, Kang BC, Kim WH, Kim DY, Lee HJ, Kim VN, Yang HK. Gastric Carcinogenesis in the miR-222/221 Transgenic Mouse Model. Cancer Res Treat. 2017 Jan; 49(1):150-160.
- Oh SY, Choi B, Lee KG, Choe HN, Lee HJ, Suh YS, Kong SH, Lee HJ, Kim WH, Yang HK. Ultrasonically Activated Shears Reduce Blood Loss without Increasing Inflammatory Reactions in Open Distal Gastrectomy for Cancer: A Randomized Controlled Study. Ann Surg Oncol 2017 Feb;24(2):494-501.
-Park H, Cho SY, Kim H, Na D, Han JY, Chae J, Park C, Park OK, Min S, Kang J, Choi B, Min J, Kwon JY, Suh YS, Kong SH, Lee HJ, Liu ET, Kim JI, Kim S, Yang HK, Lee C. Genomic alterations in BCL2L1 and DLC1 contribute to drug sensitivity in gastric cancer. Proc Natl Acad Sci U S A. 2015 Oct 6; 112(40):12492-7.
-Suh YS, Yu J, Kim BC, Choi B, Han TS, Ahn HS, Kong SH, Lee HJ, Kim WH, Yang HK. Overexpression of Plasminogen Activator Inhibitor-1 in Advanced Gastric Cancer with Aggressive Lymph Node Metastasis. Cancer Res Treat. 2015 Oct; 47(4):718-26.
-Han TS, Hur K, Xu G, Choi B, Okugawa Y, Toiyama Y, Oshima H, Oshima M, Lee HJ, Kim VN, Chang AN, Goel A, Yang HK. MicroRNA-29c mediates initiation of gastric carcinogenesis by directly targeting ITGB1. Gut. 2015 Feb; 64(2):203-14.
-Yu J, Lee HJ, Hur K, Kwak MK, Han TS, Kim WH, Song SC, Yanagihara K, Yang HK. The antitumor effect of a thermosensitive polymeric hydrogel containing paclitaxel in a peritoneal carcinomatosis model. Invest New Drugs 2012 Feb;30(1):1-7.
-Kong SH, Lee HJ, Ahn HS, Kim JW, Kim WH, Lee KU, Yang HK. Stage migration effect on survival in gastric cancer surgery with extended lymphadenectomy: the reappraisal of positive lymph node ratio as a proper N-staging. Ann Surg 2012 Jan;255(1):50-8.
-Park DJ, Kim HH, Park YS, Lee HS, Lee WW, Lee HJ, Yang HK. Simultaneous Indocyanine Green and (99m)Tc-Antimony Sulfur Colloid-Guided Laparoscopic Sentinel Basin Dissection for Gastric Cancer. Ann Surg Oncol 2011 Jan;18(1):160-5.
-Lee HJ, Nam KT, Park HS, Kim MA, Lafleur BJ, Aburatani H, Yang HK, Kim WH, Goldenring JR. Gene expression profiling of metaplastic lineages identifies CDH17 as a prognostic marker in early-stage gastric cancer. Gastroenterology 2010 Jul;139:213-225.
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