Cargando…

Underexpression of Carbamoyl Phosphate Synthetase I as Independent Unfavorable Prognostic Factor in Intrahepatic Cholangiocarcinoma: A Potential Theranostic Biomarker

Intrahepatic cholangiocarcinoma (IHCC) is the second most common malignant neoplasm of the liver. In spite of the increasing incidence worldwide, it is relatively rare in Western countries. IHCC is relatively common in Eastern and Southeastern Asia. Patients with IHCC are usually diagnosed at an adv...

Descripción completa

Detalles Bibliográficos
Autores principales: Ong, Khaa Hoo, Hsieh, Yao-Yu, Sun, Ding-Ping, Huang, Steven Kuan-Hua, Tian, Yu-Feng, Chou, Chia-Ling, Shiue, Yow-Ling, Joseph, Keva, Chang, I-Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10340233/
https://www.ncbi.nlm.nih.gov/pubmed/37443694
http://dx.doi.org/10.3390/diagnostics13132296
_version_ 1785072029671620608
author Ong, Khaa Hoo
Hsieh, Yao-Yu
Sun, Ding-Ping
Huang, Steven Kuan-Hua
Tian, Yu-Feng
Chou, Chia-Ling
Shiue, Yow-Ling
Joseph, Keva
Chang, I-Wei
author_facet Ong, Khaa Hoo
Hsieh, Yao-Yu
Sun, Ding-Ping
Huang, Steven Kuan-Hua
Tian, Yu-Feng
Chou, Chia-Ling
Shiue, Yow-Ling
Joseph, Keva
Chang, I-Wei
author_sort Ong, Khaa Hoo
collection PubMed
description Intrahepatic cholangiocarcinoma (IHCC) is the second most common malignant neoplasm of the liver. In spite of the increasing incidence worldwide, it is relatively rare in Western countries. IHCC is relatively common in Eastern and Southeastern Asia. Patients with IHCC are usually diagnosed at an advanced stage, therefore, the clinical outcome is dismal. Dysregulation of urea cycle metabolic enzyme expression is found in different types of cancers. Nevertheless, a comprehensive evaluation of genes related to the urea cycle (i.e., GO:0000050) has not been conducted in IHCC. By performing a comparative analysis of gene expression profiles, we specifically examined genes associated with the urea cycle (GO:0000050) in a publicly accessible transcriptomic dataset (GSE26566). Interestingly, CPS1 was identified as the second most prominently down-regulated gene in this context. Tumor tissues of 182 IHCC patients who underwent curative-intent hepatectomy were enrolled. The expression level of CPS1 protein in our IHCC cohort was assessed by immunohistochemical study. Subsequent to that, statistical analyses were carried out to examine the expression of CPS1 in relation to various clinicopathological factors, as well as to assess its impact on survival outcomes. We noticed that lower immunoreactivity of CPS1 in IHCC was associated with tumor progression (pT status) with statistical significance (p = 0.003). CPS1 underexpression was not only negatively correlated to overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS) and metastasis-free survival (MeFS) in univariate analysis but also an independent prognosticator to forecast poorer clinical outcome for all prognostic indices (OS, DFS, LRFS and MeFs) in patients with IHCC (all p ≤ 0.001). These results support that CPS1 may play a crucial role in IHCC oncogenesis and tumor progression and serve as a novel prognostic factor and a potential diagnostic and theranostic biomarker.
format Online
Article
Text
id pubmed-10340233
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-103402332023-07-14 Underexpression of Carbamoyl Phosphate Synthetase I as Independent Unfavorable Prognostic Factor in Intrahepatic Cholangiocarcinoma: A Potential Theranostic Biomarker Ong, Khaa Hoo Hsieh, Yao-Yu Sun, Ding-Ping Huang, Steven Kuan-Hua Tian, Yu-Feng Chou, Chia-Ling Shiue, Yow-Ling Joseph, Keva Chang, I-Wei Diagnostics (Basel) Article Intrahepatic cholangiocarcinoma (IHCC) is the second most common malignant neoplasm of the liver. In spite of the increasing incidence worldwide, it is relatively rare in Western countries. IHCC is relatively common in Eastern and Southeastern Asia. Patients with IHCC are usually diagnosed at an advanced stage, therefore, the clinical outcome is dismal. Dysregulation of urea cycle metabolic enzyme expression is found in different types of cancers. Nevertheless, a comprehensive evaluation of genes related to the urea cycle (i.e., GO:0000050) has not been conducted in IHCC. By performing a comparative analysis of gene expression profiles, we specifically examined genes associated with the urea cycle (GO:0000050) in a publicly accessible transcriptomic dataset (GSE26566). Interestingly, CPS1 was identified as the second most prominently down-regulated gene in this context. Tumor tissues of 182 IHCC patients who underwent curative-intent hepatectomy were enrolled. The expression level of CPS1 protein in our IHCC cohort was assessed by immunohistochemical study. Subsequent to that, statistical analyses were carried out to examine the expression of CPS1 in relation to various clinicopathological factors, as well as to assess its impact on survival outcomes. We noticed that lower immunoreactivity of CPS1 in IHCC was associated with tumor progression (pT status) with statistical significance (p = 0.003). CPS1 underexpression was not only negatively correlated to overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS) and metastasis-free survival (MeFS) in univariate analysis but also an independent prognosticator to forecast poorer clinical outcome for all prognostic indices (OS, DFS, LRFS and MeFs) in patients with IHCC (all p ≤ 0.001). These results support that CPS1 may play a crucial role in IHCC oncogenesis and tumor progression and serve as a novel prognostic factor and a potential diagnostic and theranostic biomarker. MDPI 2023-07-06 /pmc/articles/PMC10340233/ /pubmed/37443694 http://dx.doi.org/10.3390/diagnostics13132296 Text en © 2023 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
Ong, Khaa Hoo
Hsieh, Yao-Yu
Sun, Ding-Ping
Huang, Steven Kuan-Hua
Tian, Yu-Feng
Chou, Chia-Ling
Shiue, Yow-Ling
Joseph, Keva
Chang, I-Wei
Underexpression of Carbamoyl Phosphate Synthetase I as Independent Unfavorable Prognostic Factor in Intrahepatic Cholangiocarcinoma: A Potential Theranostic Biomarker
title Underexpression of Carbamoyl Phosphate Synthetase I as Independent Unfavorable Prognostic Factor in Intrahepatic Cholangiocarcinoma: A Potential Theranostic Biomarker
title_full Underexpression of Carbamoyl Phosphate Synthetase I as Independent Unfavorable Prognostic Factor in Intrahepatic Cholangiocarcinoma: A Potential Theranostic Biomarker
title_fullStr Underexpression of Carbamoyl Phosphate Synthetase I as Independent Unfavorable Prognostic Factor in Intrahepatic Cholangiocarcinoma: A Potential Theranostic Biomarker
title_full_unstemmed Underexpression of Carbamoyl Phosphate Synthetase I as Independent Unfavorable Prognostic Factor in Intrahepatic Cholangiocarcinoma: A Potential Theranostic Biomarker
title_short Underexpression of Carbamoyl Phosphate Synthetase I as Independent Unfavorable Prognostic Factor in Intrahepatic Cholangiocarcinoma: A Potential Theranostic Biomarker
title_sort underexpression of carbamoyl phosphate synthetase i as independent unfavorable prognostic factor in intrahepatic cholangiocarcinoma: a potential theranostic biomarker
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10340233/
https://www.ncbi.nlm.nih.gov/pubmed/37443694
http://dx.doi.org/10.3390/diagnostics13132296
work_keys_str_mv AT ongkhaahoo underexpressionofcarbamoylphosphatesynthetaseiasindependentunfavorableprognosticfactorinintrahepaticcholangiocarcinomaapotentialtheranosticbiomarker
AT hsiehyaoyu underexpressionofcarbamoylphosphatesynthetaseiasindependentunfavorableprognosticfactorinintrahepaticcholangiocarcinomaapotentialtheranosticbiomarker
AT sundingping underexpressionofcarbamoylphosphatesynthetaseiasindependentunfavorableprognosticfactorinintrahepaticcholangiocarcinomaapotentialtheranosticbiomarker
AT huangstevenkuanhua underexpressionofcarbamoylphosphatesynthetaseiasindependentunfavorableprognosticfactorinintrahepaticcholangiocarcinomaapotentialtheranosticbiomarker
AT tianyufeng underexpressionofcarbamoylphosphatesynthetaseiasindependentunfavorableprognosticfactorinintrahepaticcholangiocarcinomaapotentialtheranosticbiomarker
AT chouchialing underexpressionofcarbamoylphosphatesynthetaseiasindependentunfavorableprognosticfactorinintrahepaticcholangiocarcinomaapotentialtheranosticbiomarker
AT shiueyowling underexpressionofcarbamoylphosphatesynthetaseiasindependentunfavorableprognosticfactorinintrahepaticcholangiocarcinomaapotentialtheranosticbiomarker
AT josephkeva underexpressionofcarbamoylphosphatesynthetaseiasindependentunfavorableprognosticfactorinintrahepaticcholangiocarcinomaapotentialtheranosticbiomarker
AT changiwei underexpressionofcarbamoylphosphatesynthetaseiasindependentunfavorableprognosticfactorinintrahepaticcholangiocarcinomaapotentialtheranosticbiomarker