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High M2-TAM Infiltration and STAT3/NF-κB Signaling Pathway as a Predictive Factor for Tumor Progression and Death in Cervical Cancer.
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.
Affiliation
  • Lira GA; Cancer and Inflammation Research Laboratory, Department of Morphology, Federal University of Rio Grande do Norte Natal, Natal 59072-970, RN, Brazil.
  • de Azevedo FM; Postgraduate Program in Health Science, Federal University of Rio Grande do Norte, Natal 59072-970, RN, Brazil.
  • Lins IGDS; Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
  • Marques IL; League Against Cancer from Rio Grande do Norte, Advanced Oncology Center, Natal 59075-740, RN, Brazil.
  • Lira GA; Pathology Department, Federal University of Rio Grande do Norte, Natal 59012-570, RN, Brazil.
  • Eich C; League Against Cancer from Rio Grande do Norte, Advanced Oncology Center, Natal 59075-740, RN, Brazil.
  • de Araujo Junior RF; Postgraduate Program in Health Science, Federal University of Rio Grande do Norte, Natal 59072-970, RN, Brazil.
Cancers (Basel) ; 16(14)2024 Jul 09.
Article in En | MEDLINE | ID: mdl-39061137
ABSTRACT

INTRODUCTION:

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.

METHODS:

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.

RESULTS:

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 p < 0.0001). In addition, elevated TNM staging IV had a strong association correlation with STAT3 and NF-κB pathways (p < 0.0001), CD25 (p < 0.001), VEGFα (p < 0.001), MIF (p < 0.0001), and Ki-67 (p < 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).

CONCLUSION:

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.
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Cancers (Basel) Year: 2024 Document type: Article Affiliation country: Brazil Country of publication: Switzerland

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Cancers (Basel) Year: 2024 Document type: Article Affiliation country: Brazil Country of publication: Switzerland