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High expression of TMEM180, a novel tumour marker, is associated with poor survival in stage III colorectal cancer

BACKGROUND: Transmembrane protein 180 (TMEM180) is a newly identified colorectal cancer (CRC)-specific molecule that is expressed very rarely in normal tissue and up-regulated under hypoxic conditions. We developed a monoclonal antibody (mAb) against TMEM180 and decided to examine the medical signif...

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Autores principales: Shiraishi, Takuya, Ikeda, Koji, Tsukada, Yuichiro, Nishizawa, Yuji, Sasaki, Takeshi, Ito, Masaaki, Kojima, Motohiro, Ishii, Genichiro, Tsumura, Ryo, Saijou, Sinji, Koga, Yoshikatsu, Yasunaga, Masahiro, Matsumura, Yasuhiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989078/
https://www.ncbi.nlm.nih.gov/pubmed/33757462
http://dx.doi.org/10.1186/s12885-021-08046-6
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author Shiraishi, Takuya
Ikeda, Koji
Tsukada, Yuichiro
Nishizawa, Yuji
Sasaki, Takeshi
Ito, Masaaki
Kojima, Motohiro
Ishii, Genichiro
Tsumura, Ryo
Saijou, Sinji
Koga, Yoshikatsu
Yasunaga, Masahiro
Matsumura, Yasuhiro
author_facet Shiraishi, Takuya
Ikeda, Koji
Tsukada, Yuichiro
Nishizawa, Yuji
Sasaki, Takeshi
Ito, Masaaki
Kojima, Motohiro
Ishii, Genichiro
Tsumura, Ryo
Saijou, Sinji
Koga, Yoshikatsu
Yasunaga, Masahiro
Matsumura, Yasuhiro
author_sort Shiraishi, Takuya
collection PubMed
description BACKGROUND: Transmembrane protein 180 (TMEM180) is a newly identified colorectal cancer (CRC)-specific molecule that is expressed very rarely in normal tissue and up-regulated under hypoxic conditions. We developed a monoclonal antibody (mAb) against TMEM180 and decided to examine the medical significance using the mAb. METHODS: A total of 157 patients (86 men and 71 women; median age 63.0 years) with stage III CRC who underwent curative surgery were analyzed for TMEM180 expression as a retrospective cohort design. Immunohistochemistry with anti-TMEM180 mAb was conducted on frozen sections, and the data were evaluated for any correlation with clinicopathological indices or prognosis. SW480 CRC cells were examined to investigate the relationship between the expression of TMEM180 and tumourigenesis of xenografts. RESULTS: In total, 92 cases had low TMEM expression and 65 had high TMEM180 expression. For disease-free survival, hazard ratio in high-TMEM180 cases was 1.449 (95% confidential interval = 0.802–2.619) higher than in low-TMEM180 cases, but the difference was not significant (p = 0.219). For cancer specific survival, hazard ratio in high-TMEM180 cases was 3.302 (95% confidential interval = 1.088–10.020), significantly higher than in low-TMEM180 cases (p = 0.035). In an assay examining in vitro colony-forming activity in soft agar, SW480-WT cells clearly formed colonies, but neither KD1 nor KD2 cells did. The in vivo tumour-initiating activity of SW480 cell lines was positively correlated with the level of TMEM180 expression. CONCLUSION: These results indicate that TMEM180 is a useful marker for clinical prognosis in patients with CRC. We believe that these fundamental data warrant further basic and translational studies of TMEM180, and its mAb, for development of therapeutics against CRC.
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spelling pubmed-79890782021-03-25 High expression of TMEM180, a novel tumour marker, is associated with poor survival in stage III colorectal cancer Shiraishi, Takuya Ikeda, Koji Tsukada, Yuichiro Nishizawa, Yuji Sasaki, Takeshi Ito, Masaaki Kojima, Motohiro Ishii, Genichiro Tsumura, Ryo Saijou, Sinji Koga, Yoshikatsu Yasunaga, Masahiro Matsumura, Yasuhiro BMC Cancer Research Article BACKGROUND: Transmembrane protein 180 (TMEM180) is a newly identified colorectal cancer (CRC)-specific molecule that is expressed very rarely in normal tissue and up-regulated under hypoxic conditions. We developed a monoclonal antibody (mAb) against TMEM180 and decided to examine the medical significance using the mAb. METHODS: A total of 157 patients (86 men and 71 women; median age 63.0 years) with stage III CRC who underwent curative surgery were analyzed for TMEM180 expression as a retrospective cohort design. Immunohistochemistry with anti-TMEM180 mAb was conducted on frozen sections, and the data were evaluated for any correlation with clinicopathological indices or prognosis. SW480 CRC cells were examined to investigate the relationship between the expression of TMEM180 and tumourigenesis of xenografts. RESULTS: In total, 92 cases had low TMEM expression and 65 had high TMEM180 expression. For disease-free survival, hazard ratio in high-TMEM180 cases was 1.449 (95% confidential interval = 0.802–2.619) higher than in low-TMEM180 cases, but the difference was not significant (p = 0.219). For cancer specific survival, hazard ratio in high-TMEM180 cases was 3.302 (95% confidential interval = 1.088–10.020), significantly higher than in low-TMEM180 cases (p = 0.035). In an assay examining in vitro colony-forming activity in soft agar, SW480-WT cells clearly formed colonies, but neither KD1 nor KD2 cells did. The in vivo tumour-initiating activity of SW480 cell lines was positively correlated with the level of TMEM180 expression. CONCLUSION: These results indicate that TMEM180 is a useful marker for clinical prognosis in patients with CRC. We believe that these fundamental data warrant further basic and translational studies of TMEM180, and its mAb, for development of therapeutics against CRC. BioMed Central 2021-03-23 /pmc/articles/PMC7989078/ /pubmed/33757462 http://dx.doi.org/10.1186/s12885-021-08046-6 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Shiraishi, Takuya
Ikeda, Koji
Tsukada, Yuichiro
Nishizawa, Yuji
Sasaki, Takeshi
Ito, Masaaki
Kojima, Motohiro
Ishii, Genichiro
Tsumura, Ryo
Saijou, Sinji
Koga, Yoshikatsu
Yasunaga, Masahiro
Matsumura, Yasuhiro
High expression of TMEM180, a novel tumour marker, is associated with poor survival in stage III colorectal cancer
title High expression of TMEM180, a novel tumour marker, is associated with poor survival in stage III colorectal cancer
title_full High expression of TMEM180, a novel tumour marker, is associated with poor survival in stage III colorectal cancer
title_fullStr High expression of TMEM180, a novel tumour marker, is associated with poor survival in stage III colorectal cancer
title_full_unstemmed High expression of TMEM180, a novel tumour marker, is associated with poor survival in stage III colorectal cancer
title_short High expression of TMEM180, a novel tumour marker, is associated with poor survival in stage III colorectal cancer
title_sort high expression of tmem180, a novel tumour marker, is associated with poor survival in stage iii colorectal cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989078/
https://www.ncbi.nlm.nih.gov/pubmed/33757462
http://dx.doi.org/10.1186/s12885-021-08046-6
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