Impact of TNF-α Gene Polymorphisms on Pancreatic and Non-Small Cell Lung Cancer-Induced Cachexia in Adult Egyptian Patients: A Focus on Pathogenic Trajectories

BackgroundCachexia is a frequent syndrome in pancreatic and non-small cell lung (NSCL) cancer patients. The storm of cancer-induced inflammatory cytokines, in particular TNF-α, is a crucial pathogenic mechanism. Among the molecular alterations accused of cancer-induced cachexia, TNF-α 308 G/A (rs180...

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Autores principales:	Rana Yehia, Mona Schaalan, Dalaal M. Abdallah, Amr S. Saad, Neven Sarhan, Samira Saleh
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	pancreatic and NSCL cancer cachexia single-nucleotide polymorphism TNF-α gene miR-155 SOCS1 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/7ed54086acbd41d3b31cb39c272256d0
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spelling	oai:doaj.org-article:7ed54086acbd41d3b31cb39c272256d02021-11-30T14:23:56ZImpact of TNF-α Gene Polymorphisms on Pancreatic and Non-Small Cell Lung Cancer-Induced Cachexia in Adult Egyptian Patients: A Focus on Pathogenic Trajectories2234-943X10.3389/fonc.2021.783231https://doaj.org/article/7ed54086acbd41d3b31cb39c272256d02021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.783231/fullhttps://doaj.org/toc/2234-943XBackgroundCachexia is a frequent syndrome in pancreatic and non-small cell lung (NSCL) cancer patients. The storm of cancer-induced inflammatory cytokines, in particular TNF-α, is a crucial pathogenic mechanism. Among the molecular alterations accused of cancer-induced cachexia, TNF-α 308 G/A (rs1800629) and −1031T/C (rs1799964) are single-nucleotide polymorphisms (SNPs) within the gene encoding this pro-inflammatory cytokine. Recent studies have demonstrated the crucial role of non-coding microRNAs (miRNAs) in pathogenesis of different diseases including cachexia. Moreover, the mechanistic cytokine signaling pathway of miR-155, as a TNF-α regulator, supports the involvement of SOCS1, TAB2, and Foxp3, which are direct targets of TNF-α gene.AimA case–control study (NCT04131478) was conducted primarily to determine the incidence of TNF-α 308 G/A (rs1800629) and −1031T/C (rs1799964) gene polymorphisms in adult Egyptian patients with local/advanced or metastatic pancreatic or NSCL cancer and investigate both as cachexia risk factors. The association of gene polymorphism with cachexia severity and the expression of miR-155 in cachectic patients were analyzed. A mechanistic investigation of the cytokine signaling pathway, involving SOCS1, TAB2, and Foxp3, was also performed.ResultsIn both pancreatic and NSCL cancer cohorts, the mutant TNF-α variant of 308 G/A was positively associated with cachexia; on the contrary, that of 1031T/C was negatively associated with cachexia in the NSCL cancer patients. MiR-155 was higher in cachexia and in alignment with its severity in the cachectic group as compared with the non-cachectic group in both the pancreatic and NSCL cancer patients. Though TAB2 did not change to any significant extent in cachectic patients, the levels of SOCS1 and Foxp3 were significantly lower in the cachectic group as compared with the non-cachectic group.ConclusionCarriers of the A allele 308 G/A gene and high miR-155 are at greater risk of cachexia in both the pancreatic and NSCL cancer patients; however, the mutant variant of 1031T/C gene is protective against cachexia in the NSCL cancer patients. Finally, high levels of miR-155 in the cachectic group lead to negative feedback inhibition of both SOCS1 and Foxp3 in both the pancreatic and NSCL cancer patients.Rana YehiaMona SchaalanDalaal M. AbdallahAmr S. SaadNeven SarhanSamira SalehFrontiers Media S.A.articlepancreatic and NSCL cancercachexiasingle-nucleotide polymorphismTNF-α genemiR-155SOCS1Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	pancreatic and NSCL cancer cachexia single-nucleotide polymorphism TNF-α gene miR-155 SOCS1 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	pancreatic and NSCL cancer cachexia single-nucleotide polymorphism TNF-α gene miR-155 SOCS1 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Rana Yehia Mona Schaalan Dalaal M. Abdallah Amr S. Saad Neven Sarhan Samira Saleh Impact of TNF-α Gene Polymorphisms on Pancreatic and Non-Small Cell Lung Cancer-Induced Cachexia in Adult Egyptian Patients: A Focus on Pathogenic Trajectories
description	BackgroundCachexia is a frequent syndrome in pancreatic and non-small cell lung (NSCL) cancer patients. The storm of cancer-induced inflammatory cytokines, in particular TNF-α, is a crucial pathogenic mechanism. Among the molecular alterations accused of cancer-induced cachexia, TNF-α 308 G/A (rs1800629) and −1031T/C (rs1799964) are single-nucleotide polymorphisms (SNPs) within the gene encoding this pro-inflammatory cytokine. Recent studies have demonstrated the crucial role of non-coding microRNAs (miRNAs) in pathogenesis of different diseases including cachexia. Moreover, the mechanistic cytokine signaling pathway of miR-155, as a TNF-α regulator, supports the involvement of SOCS1, TAB2, and Foxp3, which are direct targets of TNF-α gene.AimA case–control study (NCT04131478) was conducted primarily to determine the incidence of TNF-α 308 G/A (rs1800629) and −1031T/C (rs1799964) gene polymorphisms in adult Egyptian patients with local/advanced or metastatic pancreatic or NSCL cancer and investigate both as cachexia risk factors. The association of gene polymorphism with cachexia severity and the expression of miR-155 in cachectic patients were analyzed. A mechanistic investigation of the cytokine signaling pathway, involving SOCS1, TAB2, and Foxp3, was also performed.ResultsIn both pancreatic and NSCL cancer cohorts, the mutant TNF-α variant of 308 G/A was positively associated with cachexia; on the contrary, that of 1031T/C was negatively associated with cachexia in the NSCL cancer patients. MiR-155 was higher in cachexia and in alignment with its severity in the cachectic group as compared with the non-cachectic group in both the pancreatic and NSCL cancer patients. Though TAB2 did not change to any significant extent in cachectic patients, the levels of SOCS1 and Foxp3 were significantly lower in the cachectic group as compared with the non-cachectic group.ConclusionCarriers of the A allele 308 G/A gene and high miR-155 are at greater risk of cachexia in both the pancreatic and NSCL cancer patients; however, the mutant variant of 1031T/C gene is protective against cachexia in the NSCL cancer patients. Finally, high levels of miR-155 in the cachectic group lead to negative feedback inhibition of both SOCS1 and Foxp3 in both the pancreatic and NSCL cancer patients.
format	article
author	Rana Yehia Mona Schaalan Dalaal M. Abdallah Amr S. Saad Neven Sarhan Samira Saleh
author_facet	Rana Yehia Mona Schaalan Dalaal M. Abdallah Amr S. Saad Neven Sarhan Samira Saleh
author_sort	Rana Yehia
title	Impact of TNF-α Gene Polymorphisms on Pancreatic and Non-Small Cell Lung Cancer-Induced Cachexia in Adult Egyptian Patients: A Focus on Pathogenic Trajectories
title_short	Impact of TNF-α Gene Polymorphisms on Pancreatic and Non-Small Cell Lung Cancer-Induced Cachexia in Adult Egyptian Patients: A Focus on Pathogenic Trajectories
title_full	Impact of TNF-α Gene Polymorphisms on Pancreatic and Non-Small Cell Lung Cancer-Induced Cachexia in Adult Egyptian Patients: A Focus on Pathogenic Trajectories
title_fullStr	Impact of TNF-α Gene Polymorphisms on Pancreatic and Non-Small Cell Lung Cancer-Induced Cachexia in Adult Egyptian Patients: A Focus on Pathogenic Trajectories
title_full_unstemmed	Impact of TNF-α Gene Polymorphisms on Pancreatic and Non-Small Cell Lung Cancer-Induced Cachexia in Adult Egyptian Patients: A Focus on Pathogenic Trajectories
title_sort	impact of tnf-α gene polymorphisms on pancreatic and non-small cell lung cancer-induced cachexia in adult egyptian patients: a focus on pathogenic trajectories
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/7ed54086acbd41d3b31cb39c272256d0
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Impact of TNF-α Gene Polymorphisms on Pancreatic and Non-Small Cell Lung Cancer-Induced Cachexia in Adult Egyptian Patients: A Focus on Pathogenic Trajectories

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