A Disintegrin and Metalloproteinase 9 (ADAM9) in Advanced Hepatocellular Carcinoma and Their Role as a Biomarker During Hepatocellular Carcinoma Immunotherapy
The chemotherapeutics sorafenib and regorafenib inhibit shedding of MHC class I-related chain A (MICA) from hepatocellular carcinoma (HCC) cells by suppressing a disintegrin and metalloprotease 9 (ADAM9). MICA is a ligand for natural killer (NK) group 2 member D (NKG2D) and is expressed on tumor cel...
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doaj-e5f9bc27333a4f5e956f3ea432e39c2e2020-11-25T02:01:59ZengMDPI AGCancers2072-66942020-03-0112374510.3390/cancers12030745cancers12030745A Disintegrin and Metalloproteinase 9 (ADAM9) in Advanced Hepatocellular Carcinoma and Their Role as a Biomarker During Hepatocellular Carcinoma ImmunotherapySooyeon Oh0YoungJoon Park1Hyun-Jung Lee2Jooho Lee3Soo-Hyeon Lee4Young-Seok Baek5Su-Kyung Chun6Seung-Min Lee7Mina Kim8Young-Eun Chon9Yeonjung Ha10Yuri Cho11Gi Jin Kim12Seong-Gyu Hwang13KyuBum Kwack14Chaum Life Center, CHA University School of Medicine, Seoul 06062, KoreaDepartment of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, KoreaCenter for Research & Development, CHA Advanced Research Institute, Seongnam 13488, KoreaDepartment of Gastroenterology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13496, KoreaImmunotherapy Development Team, R & D Division, CHA Biolab, Seongnam 13488, KoreaImmunotherapy Development Team, R & D Division, CHA Biolab, Seongnam 13488, KoreaDepartment of Food Science and Biotechnology, College of Life Science, CHA University, Seongnam 13488, KoreaCenter for Research & Development, CHA Advanced Research Institute, Seongnam 13488, KoreaDepartment of Gastroenterology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13496, KoreaDepartment of Gastroenterology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13496, KoreaDepartment of Gastroenterology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13496, KoreaDepartment of Gastroenterology, CHA Gangnam Medical Center, CHA University School of Medicine, Seoul 06135, KoreaDepartment of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, KoreaDepartment of Gastroenterology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13496, KoreaDepartment of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, KoreaThe chemotherapeutics sorafenib and regorafenib inhibit shedding of MHC class I-related chain A (MICA) from hepatocellular carcinoma (HCC) cells by suppressing a disintegrin and metalloprotease 9 (ADAM9). MICA is a ligand for natural killer (NK) group 2 member D (NKG2D) and is expressed on tumor cells to elicit attack by NK cells. This study measured <i>ADAM9</i> mRNA levels in blood samples of advanced HCC patients (<i>n</i> = 10). In newly diagnosed patients (<i>n</i> = 5), the plasma <i>ADAM9</i> mRNA level was significantly higher than that in healthy controls (3.001 versus 1.00, <i>p</i> < 0.05). Among four patients treated with nivolumab therapy, two patients with clinical response to nivolumab showed significant decreases in fold changes of serum <i>ADAM9</i> mRNA level from 573.98 to 262.58 and from 323.88 to 85.52 (<i>p</i> < 0.05); however, two patients with no response to nivolumab did not. Using the Cancer Genome Atlas database, we found that higher expression of <i>ADAM9</i> in tumor tissues was associated with poorer survival of HCC patients (log-rank <i>p</i> = 0.00039), while <i>ADAM10</i> and <i>ADAM17</i> exhibited no such association. In addition, <i>ADAM9</i> expression showed a positive correlation with the expression of inhibitory checkpoint molecules. This study, though small in sample size, clearly suggested that <i>ADAM9</i> mRNA might serve as biomarker predicting clinical response and that the ADAM9-MICA-NKG2D system can be a good therapeutic target for HCC immunotherapy. Future studies are warranted to validate these findings.https://www.mdpi.com/2072-6694/12/3/745hepatocellular carcinomaa disintegrin and metalloprotease 9nivolumabnatural killerimmunotherapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sooyeon Oh YoungJoon Park Hyun-Jung Lee Jooho Lee Soo-Hyeon Lee Young-Seok Baek Su-Kyung Chun Seung-Min Lee Mina Kim Young-Eun Chon Yeonjung Ha Yuri Cho Gi Jin Kim Seong-Gyu Hwang KyuBum Kwack |
spellingShingle |
Sooyeon Oh YoungJoon Park Hyun-Jung Lee Jooho Lee Soo-Hyeon Lee Young-Seok Baek Su-Kyung Chun Seung-Min Lee Mina Kim Young-Eun Chon Yeonjung Ha Yuri Cho Gi Jin Kim Seong-Gyu Hwang KyuBum Kwack A Disintegrin and Metalloproteinase 9 (ADAM9) in Advanced Hepatocellular Carcinoma and Their Role as a Biomarker During Hepatocellular Carcinoma Immunotherapy Cancers hepatocellular carcinoma a disintegrin and metalloprotease 9 nivolumab natural killer immunotherapy |
author_facet |
Sooyeon Oh YoungJoon Park Hyun-Jung Lee Jooho Lee Soo-Hyeon Lee Young-Seok Baek Su-Kyung Chun Seung-Min Lee Mina Kim Young-Eun Chon Yeonjung Ha Yuri Cho Gi Jin Kim Seong-Gyu Hwang KyuBum Kwack |
author_sort |
Sooyeon Oh |
title |
A Disintegrin and Metalloproteinase 9 (ADAM9) in Advanced Hepatocellular Carcinoma and Their Role as a Biomarker During Hepatocellular Carcinoma Immunotherapy |
title_short |
A Disintegrin and Metalloproteinase 9 (ADAM9) in Advanced Hepatocellular Carcinoma and Their Role as a Biomarker During Hepatocellular Carcinoma Immunotherapy |
title_full |
A Disintegrin and Metalloproteinase 9 (ADAM9) in Advanced Hepatocellular Carcinoma and Their Role as a Biomarker During Hepatocellular Carcinoma Immunotherapy |
title_fullStr |
A Disintegrin and Metalloproteinase 9 (ADAM9) in Advanced Hepatocellular Carcinoma and Their Role as a Biomarker During Hepatocellular Carcinoma Immunotherapy |
title_full_unstemmed |
A Disintegrin and Metalloproteinase 9 (ADAM9) in Advanced Hepatocellular Carcinoma and Their Role as a Biomarker During Hepatocellular Carcinoma Immunotherapy |
title_sort |
disintegrin and metalloproteinase 9 (adam9) in advanced hepatocellular carcinoma and their role as a biomarker during hepatocellular carcinoma immunotherapy |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2020-03-01 |
description |
The chemotherapeutics sorafenib and regorafenib inhibit shedding of MHC class I-related chain A (MICA) from hepatocellular carcinoma (HCC) cells by suppressing a disintegrin and metalloprotease 9 (ADAM9). MICA is a ligand for natural killer (NK) group 2 member D (NKG2D) and is expressed on tumor cells to elicit attack by NK cells. This study measured <i>ADAM9</i> mRNA levels in blood samples of advanced HCC patients (<i>n</i> = 10). In newly diagnosed patients (<i>n</i> = 5), the plasma <i>ADAM9</i> mRNA level was significantly higher than that in healthy controls (3.001 versus 1.00, <i>p</i> < 0.05). Among four patients treated with nivolumab therapy, two patients with clinical response to nivolumab showed significant decreases in fold changes of serum <i>ADAM9</i> mRNA level from 573.98 to 262.58 and from 323.88 to 85.52 (<i>p</i> < 0.05); however, two patients with no response to nivolumab did not. Using the Cancer Genome Atlas database, we found that higher expression of <i>ADAM9</i> in tumor tissues was associated with poorer survival of HCC patients (log-rank <i>p</i> = 0.00039), while <i>ADAM10</i> and <i>ADAM17</i> exhibited no such association. In addition, <i>ADAM9</i> expression showed a positive correlation with the expression of inhibitory checkpoint molecules. This study, though small in sample size, clearly suggested that <i>ADAM9</i> mRNA might serve as biomarker predicting clinical response and that the ADAM9-MICA-NKG2D system can be a good therapeutic target for HCC immunotherapy. Future studies are warranted to validate these findings. |
topic |
hepatocellular carcinoma a disintegrin and metalloprotease 9 nivolumab natural killer immunotherapy |
url |
https://www.mdpi.com/2072-6694/12/3/745 |
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