Perturbation of miR-146b and relevant inflammatory elements in esophageal carcinoma patients supports an immune downregulatory mechanism.
Blood
Esophageal cancer
Inflammation
MiR-146b
MicroRNA
Journal
Pathology, research and practice
ISSN: 1618-0631
Titre abrégé: Pathol Res Pract
Pays: Germany
ID NLM: 7806109
Informations de publication
Date de publication:
Sep 2021
Sep 2021
Historique:
received:
31
03
2021
revised:
10
07
2021
accepted:
17
07
2021
pubmed:
27
7
2021
medline:
1
2
2022
entrez:
26
7
2021
Statut:
ppublish
Résumé
Esophageal Cancer is known as one of the deadliest cancers worldwide with the squamous cell carcinoma (ESCC) being the predominant subtype. There is a growing body of evidence linking the dysregulated microRNA (miRNA) pathway of immune cells to the progression of several tumors. In a previous study, we investigated molecular alterations pertaining to miR-146a and some components of NF-kB signaling pathway and proposed a possible immune downregulatory mechanism in peripheral blood mononuclear cells (PBMCs) of ESCC patients. Here, we further scrutinized other components of this pathway by evaluating PBMC levels of miR-146b, TLR4, IL10, and TNFA. Gene expressions were quantified using RT-qPCR assays. To prevent the vulnerability of results to the expression instability of reference genes, nine additional transcripts were quantified, and stable reference genes for normalizing qPCR data were identified using the NormFinder and the geNorm algorithms. The efficiency-corrected normalized relative quantity values were used to compare gene expressions among study groups. The PBMC expression of miR-146b and TNFA was downregulated in ESCC patients as compared to healthy subjects. While the level of TLR4 was not different among the study groups, the PBMC level of IL10 was upregulated in ESCC patients. Logistic regression analyses coupled with the ROC curve and cross-validation analysis suggested that PBMC expression may serve as potential candidate biomarker for discriminating ESCC patients from healthy subjects. The present findings, in line with our previous report, propose a particular gene expression pattern in PBMCs of ESCC patients, providing evidence in support of an immune downregulatory mechanism.
Sections du résumé
BACKGROUND
BACKGROUND
Esophageal Cancer is known as one of the deadliest cancers worldwide with the squamous cell carcinoma (ESCC) being the predominant subtype. There is a growing body of evidence linking the dysregulated microRNA (miRNA) pathway of immune cells to the progression of several tumors. In a previous study, we investigated molecular alterations pertaining to miR-146a and some components of NF-kB signaling pathway and proposed a possible immune downregulatory mechanism in peripheral blood mononuclear cells (PBMCs) of ESCC patients. Here, we further scrutinized other components of this pathway by evaluating PBMC levels of miR-146b, TLR4, IL10, and TNFA.
METHODS
METHODS
Gene expressions were quantified using RT-qPCR assays. To prevent the vulnerability of results to the expression instability of reference genes, nine additional transcripts were quantified, and stable reference genes for normalizing qPCR data were identified using the NormFinder and the geNorm algorithms. The efficiency-corrected normalized relative quantity values were used to compare gene expressions among study groups.
RESULTS
RESULTS
The PBMC expression of miR-146b and TNFA was downregulated in ESCC patients as compared to healthy subjects. While the level of TLR4 was not different among the study groups, the PBMC level of IL10 was upregulated in ESCC patients. Logistic regression analyses coupled with the ROC curve and cross-validation analysis suggested that PBMC expression may serve as potential candidate biomarker for discriminating ESCC patients from healthy subjects.
CONCLUSION
CONCLUSIONS
The present findings, in line with our previous report, propose a particular gene expression pattern in PBMCs of ESCC patients, providing evidence in support of an immune downregulatory mechanism.
Identifiants
pubmed: 34311393
pii: S0344-0338(21)00221-1
doi: 10.1016/j.prp.2021.153560
pii:
doi:
Substances chimiques
MIRN146 microRNA, human
0
MicroRNAs
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
153560Informations de copyright
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