Exploring microsatellite instability in patients with advanced hepatocellular carcinoma and its tumor microenvironment
Abstract Background and Aim Immune checkpoint inhibitors and their combination with other agents have recently been available in advanced hepatocellular carcinoma (HCC). Hence, a thorough understanding of the tumor microenvironment based on tumor samples is yet to be achieved. This study aimed to ex...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Wiley
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/e082e4c91a2142358c016fb7ff695a59 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:e082e4c91a2142358c016fb7ff695a59 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:e082e4c91a2142358c016fb7ff695a592021-11-18T11:25:44ZExploring microsatellite instability in patients with advanced hepatocellular carcinoma and its tumor microenvironment2397-907010.1002/jgh3.12660https://doaj.org/article/e082e4c91a2142358c016fb7ff695a592021-11-01T00:00:00Zhttps://doi.org/10.1002/jgh3.12660https://doaj.org/toc/2397-9070Abstract Background and Aim Immune checkpoint inhibitors and their combination with other agents have recently been available in advanced hepatocellular carcinoma (HCC). Hence, a thorough understanding of the tumor microenvironment based on tumor samples is yet to be achieved. This study aimed to explore the tumor microenvironment in advanced HCC in terms of microsatellite instability‐high (MSI‐H) by using tumor samples from advanced HCC patients eligible for systemic therapy. Methods MSI‐H was assessed by polymerase chain reaction, and the expression of mismatch repair proteins, PD‐L1, CD8, VEGF, and HLA‐class1 was evaluated by immunohistochemistry. Whole‐exome sequencing was performed for MSI‐H tumor samples. Results Of 50 patients, one (2.0%) was confirmed with MSI‐H. In the MSI‐H advanced HCC tumor, a high tumor mutation burden, infiltration of CD8+ lymphocytes, and low expression of VEGF were identified. Although PD‐L1 expression was negative, there was shrinkage of tumor following pembrolizumab. However, another tumor nonresponsive to pembrolizumab was present simultaneously. Checking the Cancer Genome Atlas (TCGA) database, we found a similar case to this patient. The TCGA case had unique gene features of miR‐21 and miR‐155 overexpression and hypermethylation of the MSH2 gene. Conclusion We identified a very small number of MSI‐H cases in HCC using one tumor biopsy sample for each patient with advanced HCC. In addition, epigenetic aberrations possibly lead to MSI‐H in HCC patients. Since different HCC clones might coexist in the liver, sampling from multiple tumors should be considered to clarify the true proportion of MSI‐H in HCC and to analyze tumor microenvironments.Shohei MukaiHiroaki KanzakiSadahisa OgasawaraTakamasa IshinoKeita OgawaMiyuki NakagawaKisako FujiwaraHidemi UnozawaTerunao IwanagaTakafumi SakumaNaoto FujitaKeisuke KorokiKazufumi KobayashiNaoya KanogawaSoichiro KiyonoMasato NakamuraTakayuki KondoTomoko SaitoRyo NakagawaEiichiro SuzukiYoshihiko OokaRyosuke MuroyamaShingo NakamotoAkinobu TawadaTetsuhiro ChibaMakoto AraiJun KatoManayu ShiinaMasayuki OtaJun‐ichiro IkedaYuichi TakiguchiMasayuki OhtsukaNaoya KatoWileyarticlehepatocellular carcinomamicrosatellite instabilitymismatch repairPD‐L1tumor microenvironmentDiseases of the digestive system. GastroenterologyRC799-869ENJGH Open, Vol 5, Iss 11, Pp 1266-1274 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
hepatocellular carcinoma microsatellite instability mismatch repair PD‐L1 tumor microenvironment Diseases of the digestive system. Gastroenterology RC799-869 |
| spellingShingle |
hepatocellular carcinoma microsatellite instability mismatch repair PD‐L1 tumor microenvironment Diseases of the digestive system. Gastroenterology RC799-869 Shohei Mukai Hiroaki Kanzaki Sadahisa Ogasawara Takamasa Ishino Keita Ogawa Miyuki Nakagawa Kisako Fujiwara Hidemi Unozawa Terunao Iwanaga Takafumi Sakuma Naoto Fujita Keisuke Koroki Kazufumi Kobayashi Naoya Kanogawa Soichiro Kiyono Masato Nakamura Takayuki Kondo Tomoko Saito Ryo Nakagawa Eiichiro Suzuki Yoshihiko Ooka Ryosuke Muroyama Shingo Nakamoto Akinobu Tawada Tetsuhiro Chiba Makoto Arai Jun Kato Manayu Shiina Masayuki Ota Jun‐ichiro Ikeda Yuichi Takiguchi Masayuki Ohtsuka Naoya Kato Exploring microsatellite instability in patients with advanced hepatocellular carcinoma and its tumor microenvironment |
| description |
Abstract Background and Aim Immune checkpoint inhibitors and their combination with other agents have recently been available in advanced hepatocellular carcinoma (HCC). Hence, a thorough understanding of the tumor microenvironment based on tumor samples is yet to be achieved. This study aimed to explore the tumor microenvironment in advanced HCC in terms of microsatellite instability‐high (MSI‐H) by using tumor samples from advanced HCC patients eligible for systemic therapy. Methods MSI‐H was assessed by polymerase chain reaction, and the expression of mismatch repair proteins, PD‐L1, CD8, VEGF, and HLA‐class1 was evaluated by immunohistochemistry. Whole‐exome sequencing was performed for MSI‐H tumor samples. Results Of 50 patients, one (2.0%) was confirmed with MSI‐H. In the MSI‐H advanced HCC tumor, a high tumor mutation burden, infiltration of CD8+ lymphocytes, and low expression of VEGF were identified. Although PD‐L1 expression was negative, there was shrinkage of tumor following pembrolizumab. However, another tumor nonresponsive to pembrolizumab was present simultaneously. Checking the Cancer Genome Atlas (TCGA) database, we found a similar case to this patient. The TCGA case had unique gene features of miR‐21 and miR‐155 overexpression and hypermethylation of the MSH2 gene. Conclusion We identified a very small number of MSI‐H cases in HCC using one tumor biopsy sample for each patient with advanced HCC. In addition, epigenetic aberrations possibly lead to MSI‐H in HCC patients. Since different HCC clones might coexist in the liver, sampling from multiple tumors should be considered to clarify the true proportion of MSI‐H in HCC and to analyze tumor microenvironments. |
| format |
article |
| author |
Shohei Mukai Hiroaki Kanzaki Sadahisa Ogasawara Takamasa Ishino Keita Ogawa Miyuki Nakagawa Kisako Fujiwara Hidemi Unozawa Terunao Iwanaga Takafumi Sakuma Naoto Fujita Keisuke Koroki Kazufumi Kobayashi Naoya Kanogawa Soichiro Kiyono Masato Nakamura Takayuki Kondo Tomoko Saito Ryo Nakagawa Eiichiro Suzuki Yoshihiko Ooka Ryosuke Muroyama Shingo Nakamoto Akinobu Tawada Tetsuhiro Chiba Makoto Arai Jun Kato Manayu Shiina Masayuki Ota Jun‐ichiro Ikeda Yuichi Takiguchi Masayuki Ohtsuka Naoya Kato |
| author_facet |
Shohei Mukai Hiroaki Kanzaki Sadahisa Ogasawara Takamasa Ishino Keita Ogawa Miyuki Nakagawa Kisako Fujiwara Hidemi Unozawa Terunao Iwanaga Takafumi Sakuma Naoto Fujita Keisuke Koroki Kazufumi Kobayashi Naoya Kanogawa Soichiro Kiyono Masato Nakamura Takayuki Kondo Tomoko Saito Ryo Nakagawa Eiichiro Suzuki Yoshihiko Ooka Ryosuke Muroyama Shingo Nakamoto Akinobu Tawada Tetsuhiro Chiba Makoto Arai Jun Kato Manayu Shiina Masayuki Ota Jun‐ichiro Ikeda Yuichi Takiguchi Masayuki Ohtsuka Naoya Kato |
| author_sort |
Shohei Mukai |
| title |
Exploring microsatellite instability in patients with advanced hepatocellular carcinoma and its tumor microenvironment |
| title_short |
Exploring microsatellite instability in patients with advanced hepatocellular carcinoma and its tumor microenvironment |
| title_full |
Exploring microsatellite instability in patients with advanced hepatocellular carcinoma and its tumor microenvironment |
| title_fullStr |
Exploring microsatellite instability in patients with advanced hepatocellular carcinoma and its tumor microenvironment |
| title_full_unstemmed |
Exploring microsatellite instability in patients with advanced hepatocellular carcinoma and its tumor microenvironment |
| title_sort |
exploring microsatellite instability in patients with advanced hepatocellular carcinoma and its tumor microenvironment |
| publisher |
Wiley |
| publishDate |
2021 |
| url |
https://doaj.org/article/e082e4c91a2142358c016fb7ff695a59 |
| work_keys_str_mv |
AT shoheimukai exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT hiroakikanzaki exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT sadahisaogasawara exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT takamasaishino exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT keitaogawa exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT miyukinakagawa exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT kisakofujiwara exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT hidemiunozawa exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT terunaoiwanaga exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT takafumisakuma exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT naotofujita exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT keisukekoroki exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT kazufumikobayashi exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT naoyakanogawa exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT soichirokiyono exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT masatonakamura exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT takayukikondo exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT tomokosaito exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT ryonakagawa exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT eiichirosuzuki exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT yoshihikoooka exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT ryosukemuroyama exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT shingonakamoto exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT akinobutawada exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT tetsuhirochiba exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT makotoarai exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT junkato exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT manayushiina exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT masayukiota exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT junichiroikeda exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT yuichitakiguchi exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT masayukiohtsuka exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment AT naoyakato exploringmicrosatelliteinstabilityinpatientswithadvancedhepatocellularcarcinomaanditstumormicroenvironment |
| _version_ |
1718420876369592320 |