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Investigation of cell signalings and therapeutic targets in PTPRK-RSPO3 fusion-positive colorectal cancer
INTRODUCTION: Colorectal cancer (CRC) is one of the most deadly and common diseases in the world, accounting for over 881,000 casualties in 2018. The PTPRK-RSPO3 (P:R) fusion is a structural variation in CRC and well known for its ability to activate WNT signaling and tumorigenesis. However, till no...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9491571/ https://www.ncbi.nlm.nih.gov/pubmed/36129915 http://dx.doi.org/10.1371/journal.pone.0274555 |
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author | Jeong, Jae Heon Yun, Jae Won Kim, Ha Young Heo, Chan Yeong Lee, Sejoon |
author_facet | Jeong, Jae Heon Yun, Jae Won Kim, Ha Young Heo, Chan Yeong Lee, Sejoon |
author_sort | Jeong, Jae Heon |
collection | PubMed |
description | INTRODUCTION: Colorectal cancer (CRC) is one of the most deadly and common diseases in the world, accounting for over 881,000 casualties in 2018. The PTPRK-RSPO3 (P:R) fusion is a structural variation in CRC and well known for its ability to activate WNT signaling and tumorigenesis. However, till now, therapeutic targets and actionable drugs are limited in this subtype of cancer. MATERIALS AND METHOD: The purpose of this study is to identify key genes and cancer-related pathways specific for P:R fusion-positive CRC. In addition, we also inferred the actionable drugs in bioinformatics analysis using the Cancer Genome Atlas (TCGA) data. RESULTS: 2,505 genes were altered in RNA expression specific for P:R fusion-positive CRC. By pathway analysis based on the altered genes, ten major cancer-related signaling pathways (Apoptosis, Direct p53, EGFR, ErbB, JAK-STAT, tyrosine kinases, Pathways in Cancer, SCF-KIT, VEGFR, and WNT-related Pathway) were significantly altered in P:R fusion-positive CRC. Among these pathways, the most altered cancer genes (ALK, ACSL3, AXIN, MYC, TP53, GNAQ, ACVR2A, and FAS) specific for P:R fusion and involved in multiple cancer pathways were considered to have a key role in P:R fusion-positive CRC. Based on the drug-target network analysis, crizotinib, alectinib, lorlatinib, brigatinib, ceritinib, erdafitinib, infigratinib and pemigatinib were selected as putative therapeutic candidates, since they were already used in routine clinical practice in other cancer types and target genes of the drugs were involved in multiple cancer-pathways. |
format | Online Article Text |
id | pubmed-9491571 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-94915712022-09-22 Investigation of cell signalings and therapeutic targets in PTPRK-RSPO3 fusion-positive colorectal cancer Jeong, Jae Heon Yun, Jae Won Kim, Ha Young Heo, Chan Yeong Lee, Sejoon PLoS One Research Article INTRODUCTION: Colorectal cancer (CRC) is one of the most deadly and common diseases in the world, accounting for over 881,000 casualties in 2018. The PTPRK-RSPO3 (P:R) fusion is a structural variation in CRC and well known for its ability to activate WNT signaling and tumorigenesis. However, till now, therapeutic targets and actionable drugs are limited in this subtype of cancer. MATERIALS AND METHOD: The purpose of this study is to identify key genes and cancer-related pathways specific for P:R fusion-positive CRC. In addition, we also inferred the actionable drugs in bioinformatics analysis using the Cancer Genome Atlas (TCGA) data. RESULTS: 2,505 genes were altered in RNA expression specific for P:R fusion-positive CRC. By pathway analysis based on the altered genes, ten major cancer-related signaling pathways (Apoptosis, Direct p53, EGFR, ErbB, JAK-STAT, tyrosine kinases, Pathways in Cancer, SCF-KIT, VEGFR, and WNT-related Pathway) were significantly altered in P:R fusion-positive CRC. Among these pathways, the most altered cancer genes (ALK, ACSL3, AXIN, MYC, TP53, GNAQ, ACVR2A, and FAS) specific for P:R fusion and involved in multiple cancer pathways were considered to have a key role in P:R fusion-positive CRC. Based on the drug-target network analysis, crizotinib, alectinib, lorlatinib, brigatinib, ceritinib, erdafitinib, infigratinib and pemigatinib were selected as putative therapeutic candidates, since they were already used in routine clinical practice in other cancer types and target genes of the drugs were involved in multiple cancer-pathways. Public Library of Science 2022-09-21 /pmc/articles/PMC9491571/ /pubmed/36129915 http://dx.doi.org/10.1371/journal.pone.0274555 Text en © 2022 Jeong et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Jeong, Jae Heon Yun, Jae Won Kim, Ha Young Heo, Chan Yeong Lee, Sejoon Investigation of cell signalings and therapeutic targets in PTPRK-RSPO3 fusion-positive colorectal cancer |
title | Investigation of cell signalings and therapeutic targets in PTPRK-RSPO3 fusion-positive colorectal cancer |
title_full | Investigation of cell signalings and therapeutic targets in PTPRK-RSPO3 fusion-positive colorectal cancer |
title_fullStr | Investigation of cell signalings and therapeutic targets in PTPRK-RSPO3 fusion-positive colorectal cancer |
title_full_unstemmed | Investigation of cell signalings and therapeutic targets in PTPRK-RSPO3 fusion-positive colorectal cancer |
title_short | Investigation of cell signalings and therapeutic targets in PTPRK-RSPO3 fusion-positive colorectal cancer |
title_sort | investigation of cell signalings and therapeutic targets in ptprk-rspo3 fusion-positive colorectal cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9491571/ https://www.ncbi.nlm.nih.gov/pubmed/36129915 http://dx.doi.org/10.1371/journal.pone.0274555 |
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