文章：

高M2型肿瘤相关巨噬细胞浸润及STAT3/NF-κB信号通路作为宫颈癌肿瘤进展与死亡的预测因子

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

原文发布日期：9 July 2024

DOI: 10.3390/cancers16142496

类型: Article

开放获取: 是

英文摘要：

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 (allp< 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.

摘要翻译： 

引言：肿瘤微环境在宫颈癌的进展、侵袭和转移过程中起着至关重要的作用。肿瘤相关巨噬细胞是宫颈癌肿瘤微环境的重要组成部分，但其与宫颈癌进展的相关性研究仍存在争议。本研究旨在探讨宫颈癌患者中TAM浸润、STAT3/NF-κB信号通路与总生存期之间的关系。方法：在一项回顾性研究中，从数据库中筛选出691例经FIGO分期系统确诊且未接受术前治疗的宫颈癌患者。采用组织芯片技术和免疫组化方法评估TAM浸润对肿瘤进展生物标志物的影响。此外，通过Kaplan-Meier法和多变量Cox回归模型分析这些生物标志物表达水平及临床病理参数对无复发生存期和总生存期的影响。结果：高密度的间质CD163+204+TAMs通过STAT3和NF-κB通路与E-钙黏蛋白、波形蛋白、MMP9、VEGFα、Bcl-2、Ki-67、CD25、MIF、FOXP3和IL-17的表达显著相关（所有p<0.0001）。同时，TNM IV期分期升高与STAT3/NF-κB通路（p<0.0001）、CD25（p<0.001）、VEGFα（p<0.001）、MIF（p<0.0001）及Ki-67（p<0.0001）呈强相关。另一方面，SNAIL（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具有显著影响。结论：M2型TAM通过STAT3/NF-κB通路对宫颈癌进展产生重要影响，这种影响反映在临床病理特征的严重程度上，成为预后不良的重要因素。

原文链接：

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