Cargando…

Identification of Potential Biomarkers for Cancer Cachexia and Anti-Fn14 Therapy

SIMPLE SUMMARY: Cancer cachexia is an underestimated condition with huge impact on survival and quality of life for many cancer patients. Currently, there is no reliable diagnosis for this condition, particularly for cancer cachexia at an early stage. The aim of our study is to develop potential bio...

Descripción completa

Detalles Bibliográficos
Autores principales: Cao, Zhipeng, Burvenich, Ingrid J., Zhao, Kening, Senko, Clare, Glab, Jason, Fogliaro, Renee, Liu, Zhanqi, Jose, Irvin, Puthalakath, Hamsa, Hoogenraad, Nick J., Osellame, Laura D., Scott, Andrew M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9688504/
https://www.ncbi.nlm.nih.gov/pubmed/36428623
http://dx.doi.org/10.3390/cancers14225533
_version_ 1784836285195616256
author Cao, Zhipeng
Burvenich, Ingrid J.
Zhao, Kening
Senko, Clare
Glab, Jason
Fogliaro, Renee
Liu, Zhanqi
Jose, Irvin
Puthalakath, Hamsa
Hoogenraad, Nick J.
Osellame, Laura D.
Scott, Andrew M.
author_facet Cao, Zhipeng
Burvenich, Ingrid J.
Zhao, Kening
Senko, Clare
Glab, Jason
Fogliaro, Renee
Liu, Zhanqi
Jose, Irvin
Puthalakath, Hamsa
Hoogenraad, Nick J.
Osellame, Laura D.
Scott, Andrew M.
author_sort Cao, Zhipeng
collection PubMed
description SIMPLE SUMMARY: Cancer cachexia is an underestimated condition with huge impact on survival and quality of life for many cancer patients. Currently, there is no reliable diagnosis for this condition, particularly for cancer cachexia at an early stage. The aim of our study is to develop potential biomarkers that can be used not only for diagnosing cancer cachexia but also evaluating potential anti-cachexia therapy such as anti-Fn14 mAb treatment. We identified several circulating biomarkers for cancer cachexia and confirmed that LCN2 is a promising biomarker for cancer cachexia in humans. These biomarkers could accelerate both diagnosis and clinical trials for cancer cachexia. ABSTRACT: Background: Developing therapies for cancer cachexia has not been successful to date, in part due to the challenges of achieving robust quantitative measures as a readout of patient treatment. Hence, identifying biomarkers to assess the outcomes of treatments for cancer cachexia is of great interest and important for accelerating future clinical trials. Methods: We established a novel xenograft model for cancer cachexia with a cachectic human PC3* cell line, which was responsive to anti-Fn14 mAb treatment. Using RNA-seq and secretomic analysis, genes differentially expressed in cachectic and non-cachectic tumors were identified and validated by digital droplet PCR (ddPCR). Correlation analysis was performed to investigate their impact on survival in cancer patients. Results: A total of 46 genes were highly expressed in cachectic PC3* tumors, which were downregulated by anti-Fn14 mAb treatment. High expression of the top 10 candidates was correlated with low survival and high cachexia risk in different cancer types. Elevated levels of LCN2 were observed in serum samples from cachectic patients compared with non-cachectic cancer patients. Conclusion: The top 10 candidates identified in this study are candidates as potential biomarkers for cancer cachexia. The diagnostic value of LCN2 in detecting cancer cachexia is confirmed in patient samples.
format Online
Article
Text
id pubmed-9688504
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-96885042022-11-25 Identification of Potential Biomarkers for Cancer Cachexia and Anti-Fn14 Therapy Cao, Zhipeng Burvenich, Ingrid J. Zhao, Kening Senko, Clare Glab, Jason Fogliaro, Renee Liu, Zhanqi Jose, Irvin Puthalakath, Hamsa Hoogenraad, Nick J. Osellame, Laura D. Scott, Andrew M. Cancers (Basel) Article SIMPLE SUMMARY: Cancer cachexia is an underestimated condition with huge impact on survival and quality of life for many cancer patients. Currently, there is no reliable diagnosis for this condition, particularly for cancer cachexia at an early stage. The aim of our study is to develop potential biomarkers that can be used not only for diagnosing cancer cachexia but also evaluating potential anti-cachexia therapy such as anti-Fn14 mAb treatment. We identified several circulating biomarkers for cancer cachexia and confirmed that LCN2 is a promising biomarker for cancer cachexia in humans. These biomarkers could accelerate both diagnosis and clinical trials for cancer cachexia. ABSTRACT: Background: Developing therapies for cancer cachexia has not been successful to date, in part due to the challenges of achieving robust quantitative measures as a readout of patient treatment. Hence, identifying biomarkers to assess the outcomes of treatments for cancer cachexia is of great interest and important for accelerating future clinical trials. Methods: We established a novel xenograft model for cancer cachexia with a cachectic human PC3* cell line, which was responsive to anti-Fn14 mAb treatment. Using RNA-seq and secretomic analysis, genes differentially expressed in cachectic and non-cachectic tumors were identified and validated by digital droplet PCR (ddPCR). Correlation analysis was performed to investigate their impact on survival in cancer patients. Results: A total of 46 genes were highly expressed in cachectic PC3* tumors, which were downregulated by anti-Fn14 mAb treatment. High expression of the top 10 candidates was correlated with low survival and high cachexia risk in different cancer types. Elevated levels of LCN2 were observed in serum samples from cachectic patients compared with non-cachectic cancer patients. Conclusion: The top 10 candidates identified in this study are candidates as potential biomarkers for cancer cachexia. The diagnostic value of LCN2 in detecting cancer cachexia is confirmed in patient samples. MDPI 2022-11-10 /pmc/articles/PMC9688504/ /pubmed/36428623 http://dx.doi.org/10.3390/cancers14225533 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
Cao, Zhipeng
Burvenich, Ingrid J.
Zhao, Kening
Senko, Clare
Glab, Jason
Fogliaro, Renee
Liu, Zhanqi
Jose, Irvin
Puthalakath, Hamsa
Hoogenraad, Nick J.
Osellame, Laura D.
Scott, Andrew M.
Identification of Potential Biomarkers for Cancer Cachexia and Anti-Fn14 Therapy
title Identification of Potential Biomarkers for Cancer Cachexia and Anti-Fn14 Therapy
title_full Identification of Potential Biomarkers for Cancer Cachexia and Anti-Fn14 Therapy
title_fullStr Identification of Potential Biomarkers for Cancer Cachexia and Anti-Fn14 Therapy
title_full_unstemmed Identification of Potential Biomarkers for Cancer Cachexia and Anti-Fn14 Therapy
title_short Identification of Potential Biomarkers for Cancer Cachexia and Anti-Fn14 Therapy
title_sort identification of potential biomarkers for cancer cachexia and anti-fn14 therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9688504/
https://www.ncbi.nlm.nih.gov/pubmed/36428623
http://dx.doi.org/10.3390/cancers14225533
work_keys_str_mv AT caozhipeng identificationofpotentialbiomarkersforcancercachexiaandantifn14therapy
AT burvenichingridj identificationofpotentialbiomarkersforcancercachexiaandantifn14therapy
AT zhaokening identificationofpotentialbiomarkersforcancercachexiaandantifn14therapy
AT senkoclare identificationofpotentialbiomarkersforcancercachexiaandantifn14therapy
AT glabjason identificationofpotentialbiomarkersforcancercachexiaandantifn14therapy
AT fogliarorenee identificationofpotentialbiomarkersforcancercachexiaandantifn14therapy
AT liuzhanqi identificationofpotentialbiomarkersforcancercachexiaandantifn14therapy
AT joseirvin identificationofpotentialbiomarkersforcancercachexiaandantifn14therapy
AT puthalakathhamsa identificationofpotentialbiomarkersforcancercachexiaandantifn14therapy
AT hoogenraadnickj identificationofpotentialbiomarkersforcancercachexiaandantifn14therapy
AT osellamelaurad identificationofpotentialbiomarkersforcancercachexiaandantifn14therapy
AT scottandrewm identificationofpotentialbiomarkersforcancercachexiaandantifn14therapy