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Prognostic significance and immune characteristics of CMTM4 in hepatocellular carcinoma

BACKGROUND: Previous study has shown that chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family member 4 (CMTM4) can bind and maintain programmed cell death ligand 1 (PD-L1) expression to promote tumor progression by alleviating the suppression of tumor-specific T cell acti...

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Autores principales: Tan, Shengkui, Guo, Xuefeng, Bei, Chunhua, Zhang, Huixia, Li, Di, Zhu, Xiaonian, Tan, Hongzhuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9389844/
https://www.ncbi.nlm.nih.gov/pubmed/35986302
http://dx.doi.org/10.1186/s12885-022-09999-y
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author Tan, Shengkui
Guo, Xuefeng
Bei, Chunhua
Zhang, Huixia
Li, Di
Zhu, Xiaonian
Tan, Hongzhuan
author_facet Tan, Shengkui
Guo, Xuefeng
Bei, Chunhua
Zhang, Huixia
Li, Di
Zhu, Xiaonian
Tan, Hongzhuan
author_sort Tan, Shengkui
collection PubMed
description BACKGROUND: Previous study has shown that chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family member 4 (CMTM4) can bind and maintain programmed cell death ligand 1 (PD-L1) expression to promote tumor progression by alleviating the suppression of tumor-specific T cell activity, suggesting its potential role in tumor immunotherapy. However, the role of CMTM4 in tumor immunity has not been well clarified, especially in hepatocellular carcinoma (HCC). METHODS: The protein expression of CMTM4/PD-L1/CD4/CD8 was detected by immunohistochemistry (IHC) detection in 90 cases of HCC tissues. The mRNA expression profiles and related prognosis data were obtained from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC). Two immune therapy cohorts were from Imvigor210 and GSE176307. RESULTS: Though the single protein expression of CMTM4, PD-L1, CD4 or CD8 in HCC tissues by IHC detection didn’t show a significant relationship with the prognosis of HCC patients, we found that high co-expression of CMTM4/PD-L1/CD4 showed a good prognosis of HCC patients. Further Timer 2.0 analysis identified that HCC patients with high expression of CMTM4/PD-L1 and high infiltration of CD4(+) T cells had a better overall survival than those with low infiltration of CD4(+) T cells. Moreover, a series of bioinformatics analyses revealed that CMTM4-related genes posed important effects on prognosis and immunity in HCC patients, and CMTM4 had a positive correlation with infiltration of CD4(+) and CD8(+) T cells in HCC. At last, we used two immunotherapy cohorts to verify that the combination of CMTM4 with PD-L1 could improve the prognosis of tumor patients underwent immunotherapy. CONCLUSIONS: CMTM4 and PD-L1 co-expression with T cell infiltration shows prognostic significance in HCC, suggesting combined effect from multiple proteins should be considered in HCC treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-022-09999-y.
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spelling pubmed-93898442022-08-20 Prognostic significance and immune characteristics of CMTM4 in hepatocellular carcinoma Tan, Shengkui Guo, Xuefeng Bei, Chunhua Zhang, Huixia Li, Di Zhu, Xiaonian Tan, Hongzhuan BMC Cancer Research Article BACKGROUND: Previous study has shown that chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family member 4 (CMTM4) can bind and maintain programmed cell death ligand 1 (PD-L1) expression to promote tumor progression by alleviating the suppression of tumor-specific T cell activity, suggesting its potential role in tumor immunotherapy. However, the role of CMTM4 in tumor immunity has not been well clarified, especially in hepatocellular carcinoma (HCC). METHODS: The protein expression of CMTM4/PD-L1/CD4/CD8 was detected by immunohistochemistry (IHC) detection in 90 cases of HCC tissues. The mRNA expression profiles and related prognosis data were obtained from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC). Two immune therapy cohorts were from Imvigor210 and GSE176307. RESULTS: Though the single protein expression of CMTM4, PD-L1, CD4 or CD8 in HCC tissues by IHC detection didn’t show a significant relationship with the prognosis of HCC patients, we found that high co-expression of CMTM4/PD-L1/CD4 showed a good prognosis of HCC patients. Further Timer 2.0 analysis identified that HCC patients with high expression of CMTM4/PD-L1 and high infiltration of CD4(+) T cells had a better overall survival than those with low infiltration of CD4(+) T cells. Moreover, a series of bioinformatics analyses revealed that CMTM4-related genes posed important effects on prognosis and immunity in HCC patients, and CMTM4 had a positive correlation with infiltration of CD4(+) and CD8(+) T cells in HCC. At last, we used two immunotherapy cohorts to verify that the combination of CMTM4 with PD-L1 could improve the prognosis of tumor patients underwent immunotherapy. CONCLUSIONS: CMTM4 and PD-L1 co-expression with T cell infiltration shows prognostic significance in HCC, suggesting combined effect from multiple proteins should be considered in HCC treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-022-09999-y. BioMed Central 2022-08-19 /pmc/articles/PMC9389844/ /pubmed/35986302 http://dx.doi.org/10.1186/s12885-022-09999-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://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
Tan, Shengkui
Guo, Xuefeng
Bei, Chunhua
Zhang, Huixia
Li, Di
Zhu, Xiaonian
Tan, Hongzhuan
Prognostic significance and immune characteristics of CMTM4 in hepatocellular carcinoma
title Prognostic significance and immune characteristics of CMTM4 in hepatocellular carcinoma
title_full Prognostic significance and immune characteristics of CMTM4 in hepatocellular carcinoma
title_fullStr Prognostic significance and immune characteristics of CMTM4 in hepatocellular carcinoma
title_full_unstemmed Prognostic significance and immune characteristics of CMTM4 in hepatocellular carcinoma
title_short Prognostic significance and immune characteristics of CMTM4 in hepatocellular carcinoma
title_sort prognostic significance and immune characteristics of cmtm4 in hepatocellular carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9389844/
https://www.ncbi.nlm.nih.gov/pubmed/35986302
http://dx.doi.org/10.1186/s12885-022-09999-y
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