High M2-TAM Infiltration and STAT3/NF-κB Signaling Pathway as a Predictive Factor for Tumor Progression and Death in Cervical Cancer

High M2-TAM Infiltration and STAT3/NF-κB Signaling Pathway as a Predictive Factor for Tumor Progression and Death in Cervical Cancer

The tumor microenvironment (TME) plays a crucial role in the progression, invasion, and metastasis of cervical carcinoma (CC). Tumor-associated macrophages (TAMs) are significant components of the CC TME, but studies on their correlation with CC progression are still controversial. This study aimed...

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Bibliographic Details
Published in:Cancers Vol. 16; no. 14; p. 2496
Main Authors: Lira, George Alexandre, de Azevedo, Fábio Medeiros, Lins, Ingrid Gabrielle Dos Santos, Marques, Isabelle de Lima, Lira, Giovanna Afonso, Eich, Christina, de Araujo Junior, Raimundo Fernandes
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 09-07-2024
Subjects:
Age
Bcl-2 protein
Biomarkers
Brain cancer
Cancer
CD163 antigen
CD25 antigen
Cervical cancer
Cervical carcinoma
Development and progression
E-cadherin
Foxp3 protein
Gelatinase B
Immunohistochemistry
Infiltration
Lymphatic system
Macrophages
Medical prognosis
Metastases
Metastasis
NF-κB protein
Oncology, Experimental
Patients
Regression analysis
Signal transduction
Software
Stat3 protein
Statistical analysis
Tumor microenvironment
Tumors
Vimentin
Brazil
United States > US
recurrence
overall survival
M2-TAM
tumor progression
cervical cancer
STAT3
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Summary:The tumor microenvironment (TME) plays a crucial role in the progression, invasion, and metastasis of cervical carcinoma (CC). Tumor-associated macrophages (TAMs) are significant components of the CC TME, but studies on their correlation with CC progression are still controversial. This study aimed to investigate the relationship between TAM infiltration, the STAT3/NF-κB signaling pathway, and Overall Survival (OS) in CC patients. In a retrospective study, 691 CC patients who had received a definitive histopathologic diagnosis of CC scored by the FIGO staging system and not undergone preoperative treatment were selected from a database. The effect of TAM infiltration on tumor progression biomarkers using Tissue Microarray (TMA) and immunohistochemistry was evaluated. Furthermore, the impact of the expression of these biomarkers and clinical-pathological parameters on recurrence-free (RF) and OS using Kaplan-Meier and multivariable Cox regression methods was also analyzed. High stromal CD163 + 204 + TAMs density and via STAT3 and NF-κB pathways was relevant to the expression of E-cadherin, Vimentin, MMP9, VEGFα, Bcl-2, Ki-67, CD25, MIF, FOXP3, and IL-17 (all < 0.0001). In addition, elevated TNM staging IV had a strong association correlation with STAT3 and NF-κB pathways ( < 0.0001), CD25 ( < 0.001), VEGFα ( < 0.001), MIF ( < 0.0001), and Ki-67 ( < 0.0001). On the other hand, overall and recurrence survival was shown to be strongly influenced by the expression of SNAIL (HR = 1.52), E-cadherin (HR = 1.78), and Ki-67 (HR = 1.44). M2-TAM and via STAT3/NF-κB pathways had a strong effect on CC tumor progression which reverberated in the severity of clinicopathological findings, becoming an important factor of poor prognosis.
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ISSN:2072-6694
2072-6694
DOI:10.3390/cancers16142496