Cargando…
ORC6, a novel prognostic biomarker, correlates with T regulatory cell infiltration in prostate adenocarcinoma: a pan-cancer analysis
BACKGROUND: The origin recognition complex (ORC), a six-subunit DNA-binding complex, participates in DNA replication in cancer cells. Specifically in prostate cancers, ORC participates the androgen receptor (AR) regulated genomic amplification and tumor proliferation throughout the entire cell cycle...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10053432/ https://www.ncbi.nlm.nih.gov/pubmed/36978046 http://dx.doi.org/10.1186/s12885-023-10763-z |
_version_ | 1785015412265582592 |
---|---|
author | Lin, Yuan Zhang, Ying Tuo, Zhouting Gao, Liang Ding, Demao Bi, Liangkuan Yu, Dexin Lv, Zhengmei Wang, Jiani Chen, Xin |
author_facet | Lin, Yuan Zhang, Ying Tuo, Zhouting Gao, Liang Ding, Demao Bi, Liangkuan Yu, Dexin Lv, Zhengmei Wang, Jiani Chen, Xin |
author_sort | Lin, Yuan |
collection | PubMed |
description | BACKGROUND: The origin recognition complex (ORC), a six-subunit DNA-binding complex, participates in DNA replication in cancer cells. Specifically in prostate cancers, ORC participates the androgen receptor (AR) regulated genomic amplification and tumor proliferation throughout the entire cell cycle. Of note, ORC6, the smallest subunit of ORC, has been reported to be dysregulated in some types of cancers (including prostate cancer), however, its prognostic and immunological significances remain yet to be elucidated. METHODS: In the current study, we comprehensively investigated the potential prognostic and immunological role of ORC6 in 33 human tumors using multiple databases, such as TCGA, Genotype-Tissue Expression, CCLE, UCSC Xena, cBioPortal, Human Protein Atlas, GeneCards, STRING, MSigDB, TISIDB, and TIMER2 databases. RESULTS: ORC6 expression was significantly upregulated in 29 types of cancers compared to the corresponding normal adjacent tissues. ORC6 overexpression correlated with higher stage and worse prognostic outcomes in most cancer types analyzed. Additionally, ORC6 was involved in the cell cycle pathway, DNA replication, and mismatch repair pathways in most tumor types. A negative correlation was observed between the tumor endothelial cell infiltration and ORC6 expression in almost all tumors, whereas the immune infiltration of T regulatory cell was noted to be statistically positively correlated with the expression of ORC6 in prostate cancer tissues. Furthermore, in most tumor types, immunosuppression-related genes, especially TGFBR1 and PD-L1 (CD274), exhibited a specific correlation with the expression of ORC6. CONCLUSIONS: This comprehensive pan-cancer analysis revealed that ORC6 expression serves as a prognostic biomarker and that ORC6 is involved in the regulation of various biological pathways, the tumor microenvironment, and the immunosuppression status in several human cancers, suggesting its potential diagnostic, prognostic, and therapeutic value in pan-cancer, especially in prostate adenocarcinoma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10763-z. |
format | Online Article Text |
id | pubmed-10053432 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-100534322023-03-30 ORC6, a novel prognostic biomarker, correlates with T regulatory cell infiltration in prostate adenocarcinoma: a pan-cancer analysis Lin, Yuan Zhang, Ying Tuo, Zhouting Gao, Liang Ding, Demao Bi, Liangkuan Yu, Dexin Lv, Zhengmei Wang, Jiani Chen, Xin BMC Cancer Research BACKGROUND: The origin recognition complex (ORC), a six-subunit DNA-binding complex, participates in DNA replication in cancer cells. Specifically in prostate cancers, ORC participates the androgen receptor (AR) regulated genomic amplification and tumor proliferation throughout the entire cell cycle. Of note, ORC6, the smallest subunit of ORC, has been reported to be dysregulated in some types of cancers (including prostate cancer), however, its prognostic and immunological significances remain yet to be elucidated. METHODS: In the current study, we comprehensively investigated the potential prognostic and immunological role of ORC6 in 33 human tumors using multiple databases, such as TCGA, Genotype-Tissue Expression, CCLE, UCSC Xena, cBioPortal, Human Protein Atlas, GeneCards, STRING, MSigDB, TISIDB, and TIMER2 databases. RESULTS: ORC6 expression was significantly upregulated in 29 types of cancers compared to the corresponding normal adjacent tissues. ORC6 overexpression correlated with higher stage and worse prognostic outcomes in most cancer types analyzed. Additionally, ORC6 was involved in the cell cycle pathway, DNA replication, and mismatch repair pathways in most tumor types. A negative correlation was observed between the tumor endothelial cell infiltration and ORC6 expression in almost all tumors, whereas the immune infiltration of T regulatory cell was noted to be statistically positively correlated with the expression of ORC6 in prostate cancer tissues. Furthermore, in most tumor types, immunosuppression-related genes, especially TGFBR1 and PD-L1 (CD274), exhibited a specific correlation with the expression of ORC6. CONCLUSIONS: This comprehensive pan-cancer analysis revealed that ORC6 expression serves as a prognostic biomarker and that ORC6 is involved in the regulation of various biological pathways, the tumor microenvironment, and the immunosuppression status in several human cancers, suggesting its potential diagnostic, prognostic, and therapeutic value in pan-cancer, especially in prostate adenocarcinoma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10763-z. BioMed Central 2023-03-29 /pmc/articles/PMC10053432/ /pubmed/36978046 http://dx.doi.org/10.1186/s12885-023-10763-z Text en © The Author(s) 2023 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 Lin, Yuan Zhang, Ying Tuo, Zhouting Gao, Liang Ding, Demao Bi, Liangkuan Yu, Dexin Lv, Zhengmei Wang, Jiani Chen, Xin ORC6, a novel prognostic biomarker, correlates with T regulatory cell infiltration in prostate adenocarcinoma: a pan-cancer analysis |
title | ORC6, a novel prognostic biomarker, correlates with T regulatory cell infiltration in prostate adenocarcinoma: a pan-cancer analysis |
title_full | ORC6, a novel prognostic biomarker, correlates with T regulatory cell infiltration in prostate adenocarcinoma: a pan-cancer analysis |
title_fullStr | ORC6, a novel prognostic biomarker, correlates with T regulatory cell infiltration in prostate adenocarcinoma: a pan-cancer analysis |
title_full_unstemmed | ORC6, a novel prognostic biomarker, correlates with T regulatory cell infiltration in prostate adenocarcinoma: a pan-cancer analysis |
title_short | ORC6, a novel prognostic biomarker, correlates with T regulatory cell infiltration in prostate adenocarcinoma: a pan-cancer analysis |
title_sort | orc6, a novel prognostic biomarker, correlates with t regulatory cell infiltration in prostate adenocarcinoma: a pan-cancer analysis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10053432/ https://www.ncbi.nlm.nih.gov/pubmed/36978046 http://dx.doi.org/10.1186/s12885-023-10763-z |
work_keys_str_mv | AT linyuan orc6anovelprognosticbiomarkercorrelateswithtregulatorycellinfiltrationinprostateadenocarcinomaapancanceranalysis AT zhangying orc6anovelprognosticbiomarkercorrelateswithtregulatorycellinfiltrationinprostateadenocarcinomaapancanceranalysis AT tuozhouting orc6anovelprognosticbiomarkercorrelateswithtregulatorycellinfiltrationinprostateadenocarcinomaapancanceranalysis AT gaoliang orc6anovelprognosticbiomarkercorrelateswithtregulatorycellinfiltrationinprostateadenocarcinomaapancanceranalysis AT dingdemao orc6anovelprognosticbiomarkercorrelateswithtregulatorycellinfiltrationinprostateadenocarcinomaapancanceranalysis AT biliangkuan orc6anovelprognosticbiomarkercorrelateswithtregulatorycellinfiltrationinprostateadenocarcinomaapancanceranalysis AT yudexin orc6anovelprognosticbiomarkercorrelateswithtregulatorycellinfiltrationinprostateadenocarcinomaapancanceranalysis AT lvzhengmei orc6anovelprognosticbiomarkercorrelateswithtregulatorycellinfiltrationinprostateadenocarcinomaapancanceranalysis AT wangjiani orc6anovelprognosticbiomarkercorrelateswithtregulatorycellinfiltrationinprostateadenocarcinomaapancanceranalysis AT chenxin orc6anovelprognosticbiomarkercorrelateswithtregulatorycellinfiltrationinprostateadenocarcinomaapancanceranalysis |