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
Cancer and Inflammation Research Laboratory, Department of Morphology, Federal University of Rio Grande do Norte Natal, Natal 59072-970, RN, Brazil.
Postgraduate Program in Health Science, Federal University of Rio Grande do Norte, Natal 59072-970, RN, Brazil.
Cancers (Basel). 2024 Jul 9;16(14):2496. doi: 10.3390/cancers16142496.
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.
肿瘤微环境（TME）在宫颈癌（CC）的进展、侵袭和转移中起着关键作用。肿瘤相关巨噬细胞（TAM）是CC肿瘤微环境的重要组成部分，但关于它们与CC进展相关性的研究仍存在争议。本研究旨在探讨CC患者中TAM浸润、STAT3/NF-κB信号通路与总生存期（OS）之间的关系。
在一项回顾性研究中，从数据库中选取691例经FIGO分期系统确诊为CC且未接受术前治疗的患者。使用组织芯片（TMA）和免疫组化评估TAM浸润对肿瘤进展生物标志物的影响。此外，还采用Kaplan-Meier法和多变量Cox回归分析这些生物标志物的表达及临床病理参数对无复发生存期（RF）和总生存期的影响。
基质中CD163 + 204 + TAM高密度以及通过STAT3和NF-κB途径与E-钙黏蛋白、波形蛋白、基质金属蛋白酶9、血管内皮生长因子α、Bcl-2、Ki-67、CD25、巨噬细胞移动抑制因子、叉头框蛋白P3和白细胞介素-17的表达相关（均P < 0.0001）。此外，TNM分期IV期升高与STAT3和NF-κB途径（P < 0.0001）、CD25（P < 0.001）、血管内皮生长因子α（P < 0.001）、巨噬细胞移动抑制因子（P < 0.0001）和Ki-67（P < 0.0001）有很强的相关性。另一方面，SNAIL（风险比[HR]=1.52）、E-钙黏蛋白（HR = 1.78）和Ki-67（HR = 1.44）的表达对总生存期和无复发生存期有显著影响。
M2-TAM以及通过STAT3/NF-κB途径对CC肿瘤进展有显著影响，这在临床病理结果的严重程度中得到体现，成为预后不良的重要因素。
