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PCDH1, a poor prognostic biomarker and potential target for pancreatic adenocarcinoma metastatic therapy

BACKGROUND: Pancreatic adenocarcinoma (PAAD) is an aggressive solid tumour characterised by few early symptoms, high mortality, and lack of effective treatment. Therefore, it is important to identify new potential therapeutic targets and prognostic biomarkers of PAAD. METHODS: The Cancer Genome Atla...

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Autores principales: Du, Xingyi, Yi, Xiaoyu, Zou, Xiaocui, Chen, Yuan, Tai, Yanhong, Ren, Xuhong, He, Xinhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10642060/
https://www.ncbi.nlm.nih.gov/pubmed/37957639
http://dx.doi.org/10.1186/s12885-023-11474-1
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author Du, Xingyi
Yi, Xiaoyu
Zou, Xiaocui
Chen, Yuan
Tai, Yanhong
Ren, Xuhong
He, Xinhua
author_facet Du, Xingyi
Yi, Xiaoyu
Zou, Xiaocui
Chen, Yuan
Tai, Yanhong
Ren, Xuhong
He, Xinhua
author_sort Du, Xingyi
collection PubMed
description BACKGROUND: Pancreatic adenocarcinoma (PAAD) is an aggressive solid tumour characterised by few early symptoms, high mortality, and lack of effective treatment. Therefore, it is important to identify new potential therapeutic targets and prognostic biomarkers of PAAD. METHODS: The Cancer Genome Atlas and Genotype-Tissue Expression databases were used to identify the expression and prognostic model of protocadherin 1 (PCDH1). The prognostic performance of risk factors and diagnosis of patients with PAAD were evaluated by regression analysis, nomogram, and receiver operating characteristic curve. Paraffin sections were collected from patients for immunohistochemistry (IHC) analysis. The expression of PCDH1 in cells obtained from primary tumours or metastatic biopsies was identified using single-cell RNA sequencing (scRNA-seq). Real-time quantitative polymerase chain reaction (qPCR) and western blotting were used to verify PCDH1 expression levels and the inhibitory effects of the compounds. RESULTS: The RNA and protein levels of PCDH1 were significantly higher in PAAD cells than in normal pancreatic ductal cells, similar to those observed in tissue sections from patients with PAAD. Aberrant methylation of the CpG site cg19767205 and micro-RNA (miRNA) hsa-miR-124-1 may be important reasons for the high PCDH1 expression in PAAD. Up-regulated PCDH1 promotes pancreatic cancer cell metastasis. The RNA levels of PCDH1 were significantly down-regulated following flutamide treatment. Flutamide reduced the percentage of PCDH1 RNA level in PAAD cells Panc-0813 to < 50%. In addition, the PCDH1 protein was significantly down-regulated after Panc-0813 cells were incubated with 20 µM flutamide and proves to be a potential therapeutic intervention for PAAD. CONCLUSION: PCDH1 is a key prognostic biomarker and promoter of PAAD metastasis. Additionally, flutamide may serve as a novel compound that down-regulates PCDH1 expression as a potential treatment for combating PAAD progression and metastasis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-11474-1.
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spelling pubmed-106420602023-11-14 PCDH1, a poor prognostic biomarker and potential target for pancreatic adenocarcinoma metastatic therapy Du, Xingyi Yi, Xiaoyu Zou, Xiaocui Chen, Yuan Tai, Yanhong Ren, Xuhong He, Xinhua BMC Cancer Research BACKGROUND: Pancreatic adenocarcinoma (PAAD) is an aggressive solid tumour characterised by few early symptoms, high mortality, and lack of effective treatment. Therefore, it is important to identify new potential therapeutic targets and prognostic biomarkers of PAAD. METHODS: The Cancer Genome Atlas and Genotype-Tissue Expression databases were used to identify the expression and prognostic model of protocadherin 1 (PCDH1). The prognostic performance of risk factors and diagnosis of patients with PAAD were evaluated by regression analysis, nomogram, and receiver operating characteristic curve. Paraffin sections were collected from patients for immunohistochemistry (IHC) analysis. The expression of PCDH1 in cells obtained from primary tumours or metastatic biopsies was identified using single-cell RNA sequencing (scRNA-seq). Real-time quantitative polymerase chain reaction (qPCR) and western blotting were used to verify PCDH1 expression levels and the inhibitory effects of the compounds. RESULTS: The RNA and protein levels of PCDH1 were significantly higher in PAAD cells than in normal pancreatic ductal cells, similar to those observed in tissue sections from patients with PAAD. Aberrant methylation of the CpG site cg19767205 and micro-RNA (miRNA) hsa-miR-124-1 may be important reasons for the high PCDH1 expression in PAAD. Up-regulated PCDH1 promotes pancreatic cancer cell metastasis. The RNA levels of PCDH1 were significantly down-regulated following flutamide treatment. Flutamide reduced the percentage of PCDH1 RNA level in PAAD cells Panc-0813 to < 50%. In addition, the PCDH1 protein was significantly down-regulated after Panc-0813 cells were incubated with 20 µM flutamide and proves to be a potential therapeutic intervention for PAAD. CONCLUSION: PCDH1 is a key prognostic biomarker and promoter of PAAD metastasis. Additionally, flutamide may serve as a novel compound that down-regulates PCDH1 expression as a potential treatment for combating PAAD progression and metastasis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-11474-1. BioMed Central 2023-11-13 /pmc/articles/PMC10642060/ /pubmed/37957639 http://dx.doi.org/10.1186/s12885-023-11474-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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
Du, Xingyi
Yi, Xiaoyu
Zou, Xiaocui
Chen, Yuan
Tai, Yanhong
Ren, Xuhong
He, Xinhua
PCDH1, a poor prognostic biomarker and potential target for pancreatic adenocarcinoma metastatic therapy
title PCDH1, a poor prognostic biomarker and potential target for pancreatic adenocarcinoma metastatic therapy
title_full PCDH1, a poor prognostic biomarker and potential target for pancreatic adenocarcinoma metastatic therapy
title_fullStr PCDH1, a poor prognostic biomarker and potential target for pancreatic adenocarcinoma metastatic therapy
title_full_unstemmed PCDH1, a poor prognostic biomarker and potential target for pancreatic adenocarcinoma metastatic therapy
title_short PCDH1, a poor prognostic biomarker and potential target for pancreatic adenocarcinoma metastatic therapy
title_sort pcdh1, a poor prognostic biomarker and potential target for pancreatic adenocarcinoma metastatic therapy
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10642060/
https://www.ncbi.nlm.nih.gov/pubmed/37957639
http://dx.doi.org/10.1186/s12885-023-11474-1
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