Cargando…

PBK/TOPK Is a Favorable Prognostic Biomarker Correlated with Antitumor Immunity in Colon Cancers

Immune checkpoint inhibitor therapy has proven efficacy in a subset of colon cancer patients featuring a deficient DNA mismatch repair system or a high microsatellite instability profile. However, there is high demand for more effective biomarkers to expand the colon cancer population responding to...

Descripción completa

Detalles Bibliográficos
Autores principales: Lee, Dong-Hee, Jeong, Yu-Jeong, Won, Ju-Young, Sim, Hye-In, Park, Yoon, Jin, Hyung-Seung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8869639/
https://www.ncbi.nlm.nih.gov/pubmed/35203508
http://dx.doi.org/10.3390/biomedicines10020299
_version_ 1784656545415430144
author Lee, Dong-Hee
Jeong, Yu-Jeong
Won, Ju-Young
Sim, Hye-In
Park, Yoon
Jin, Hyung-Seung
author_facet Lee, Dong-Hee
Jeong, Yu-Jeong
Won, Ju-Young
Sim, Hye-In
Park, Yoon
Jin, Hyung-Seung
author_sort Lee, Dong-Hee
collection PubMed
description Immune checkpoint inhibitor therapy has proven efficacy in a subset of colon cancer patients featuring a deficient DNA mismatch repair system or a high microsatellite instability profile. However, there is high demand for more effective biomarkers to expand the colon cancer population responding to ICI therapy. PBK/TOPK, a serine/threonine kinase, plays a role in cell cycle regulation and mitotic progression. Here, we investigated the correlation between PBK/TOPK expression and tumor immunity and its prognostic value in colon cancer. Based on large-scale bioinformatics analysis, we discovered that elevated PBK/TOPK expression predicted a favorable outcome in patients with colon cancer and was positively associated with immune infiltration levels of CD8+ T cells, CD4+ T cells, natural killer cells, and M1 macrophages. In contrast, a negative correlation was found between PBK/TOPK expression and immune suppressor cells, including regulatory T cells and M2 macrophages. Furthermore, the expression of PBK/TOPK was correlated with the expression of T-cell cytotoxicity genes in colon cancer. Additionally, high PBK/TOPK expression was associated with mutations in DNA damage repair genes, and thus with increased tumor mutation and neoantigen burden. These findings suggest that PBK/TOPK may serve as a prognostic and predictive biomarker for immunotherapy in colon cancer.
format Online
Article
Text
id pubmed-8869639
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-88696392022-02-25 PBK/TOPK Is a Favorable Prognostic Biomarker Correlated with Antitumor Immunity in Colon Cancers Lee, Dong-Hee Jeong, Yu-Jeong Won, Ju-Young Sim, Hye-In Park, Yoon Jin, Hyung-Seung Biomedicines Article Immune checkpoint inhibitor therapy has proven efficacy in a subset of colon cancer patients featuring a deficient DNA mismatch repair system or a high microsatellite instability profile. However, there is high demand for more effective biomarkers to expand the colon cancer population responding to ICI therapy. PBK/TOPK, a serine/threonine kinase, plays a role in cell cycle regulation and mitotic progression. Here, we investigated the correlation between PBK/TOPK expression and tumor immunity and its prognostic value in colon cancer. Based on large-scale bioinformatics analysis, we discovered that elevated PBK/TOPK expression predicted a favorable outcome in patients with colon cancer and was positively associated with immune infiltration levels of CD8+ T cells, CD4+ T cells, natural killer cells, and M1 macrophages. In contrast, a negative correlation was found between PBK/TOPK expression and immune suppressor cells, including regulatory T cells and M2 macrophages. Furthermore, the expression of PBK/TOPK was correlated with the expression of T-cell cytotoxicity genes in colon cancer. Additionally, high PBK/TOPK expression was associated with mutations in DNA damage repair genes, and thus with increased tumor mutation and neoantigen burden. These findings suggest that PBK/TOPK may serve as a prognostic and predictive biomarker for immunotherapy in colon cancer. MDPI 2022-01-27 /pmc/articles/PMC8869639/ /pubmed/35203508 http://dx.doi.org/10.3390/biomedicines10020299 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Dong-Hee
Jeong, Yu-Jeong
Won, Ju-Young
Sim, Hye-In
Park, Yoon
Jin, Hyung-Seung
PBK/TOPK Is a Favorable Prognostic Biomarker Correlated with Antitumor Immunity in Colon Cancers
title PBK/TOPK Is a Favorable Prognostic Biomarker Correlated with Antitumor Immunity in Colon Cancers
title_full PBK/TOPK Is a Favorable Prognostic Biomarker Correlated with Antitumor Immunity in Colon Cancers
title_fullStr PBK/TOPK Is a Favorable Prognostic Biomarker Correlated with Antitumor Immunity in Colon Cancers
title_full_unstemmed PBK/TOPK Is a Favorable Prognostic Biomarker Correlated with Antitumor Immunity in Colon Cancers
title_short PBK/TOPK Is a Favorable Prognostic Biomarker Correlated with Antitumor Immunity in Colon Cancers
title_sort pbk/topk is a favorable prognostic biomarker correlated with antitumor immunity in colon cancers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8869639/
https://www.ncbi.nlm.nih.gov/pubmed/35203508
http://dx.doi.org/10.3390/biomedicines10020299
work_keys_str_mv AT leedonghee pbktopkisafavorableprognosticbiomarkercorrelatedwithantitumorimmunityincoloncancers
AT jeongyujeong pbktopkisafavorableprognosticbiomarkercorrelatedwithantitumorimmunityincoloncancers
AT wonjuyoung pbktopkisafavorableprognosticbiomarkercorrelatedwithantitumorimmunityincoloncancers
AT simhyein pbktopkisafavorableprognosticbiomarkercorrelatedwithantitumorimmunityincoloncancers
AT parkyoon pbktopkisafavorableprognosticbiomarkercorrelatedwithantitumorimmunityincoloncancers
AT jinhyungseung pbktopkisafavorableprognosticbiomarkercorrelatedwithantitumorimmunityincoloncancers