背景:肿瘤微环境(TME)在进展中起着至关重要的作用,入侵,和宫颈癌转移(CC)。肿瘤相关巨噬细胞(TAM)是CCTME的重要组成部分,但是关于它们与CC进展的相关性的研究仍然存在争议。本研究旨在探讨TAM浸润之间的关系,STAT3/NF-κB信号通路,CC患者的总生存期(OS)。
方法:在一项回顾性研究中,从数据库中选择691例CC患者,这些患者接受了由FIGO分期系统评分的CC的明确组织病理学诊断,并且没有接受术前治疗。使用组织微阵列(TMA)和免疫组织化学评估TAM浸润对肿瘤进展生物标志物的影响。此外,还使用Kaplan-Meier和多变量Cox回归方法分析了这些生物标志物的表达和临床-病理参数对无复发(RF)和OS的影响.
结果:高基质CD163+204+TAMs密度和通过STAT3和NF-κB途径与E-cadherin的表达有关,Vimentin,MMP9,VEGFα,Bcl-2,Ki-67,CD25,MIF,FOXP3和IL-17(所有p<0.0001)。此外,升高的TNM分期IV与STAT3和NF-κB通路有很强的相关性(p<0.0001),CD25(p<0.001),VEGFα(p<0.001),MIF(p<0.0001),和Ki-67(p<0.0001)。另一方面,SNAIL的表达对总生存期和复发生存期有很大影响(HR=1.52),E-cadherin(HR=1.78),Ki-67(HR=1.44)。
结论:M2-TAM和通过STAT3/NF-κB通路对CC肿瘤进展有很强的影响,这反映了临床病理结果的严重程度,成为预后不良的重要因素。
BACKGROUND: 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).
CONCLUSIONS: 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.