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CD47、CD68和CD163表达水平在局部晚期和寡转移鼻咽癌中的预后意义及其与混合淋巴细胞反应(MLR)和巨噬细胞吞噬率(MAR)的关系

The Prognostic Significance of CD47, CD68, and CD163 Expression Levels and Their Relationship with MLR and MAR in Locally Advanced and Oligometastatic Nasopharyngeal Carcinoma.

作者信息

Aydin Asim Armagan, Yuceer Ramazan Oguz, Yildirim Senay, Unlu Ahmet, Kayikcioglu Erkan, Kocer Murat

机构信息

Department of Clinical Oncology, Health Sciences University Antalya Education and Research Hospital, Antalya 07100, Turkey.

Department of Pathology, Cumhuriyet University School of Medicine, Sivas 58140, Turkey.

出版信息

Diagnostics (Basel). 2024 Nov 24;14(23):2648. doi: 10.3390/diagnostics14232648.

Abstract

BACKGROUND

This study aimed to assess the prognostic and predictive implications of CD47, CD68, and CD163, biomarkers of tumor-associated macrophages (TAMs), on the treatment efficacy and clinical outcomes of nasopharyngeal carcinoma (NPC). Additionally, the prognostic value of TAM-related indices, such as the monocyte-to-lymphocyte ratio (MLR) and monocyte-to-albumin ratio (MAR), was evaluated.

METHODS

A retrospective cohort of 54 patients with locally advanced or oligometastatic NPC treated with concurrent chemoradiotherapy (CCRT), with or without induction chemotherapy, was analyzed. Patients were categorized based on the cumulative expression scores for CD47, CD68, and CD163: negative/low (0-3 points) and high (4-6 points). MLR and MAR were also stratified as low MLR (<0.545) vs. high MLR (≥0.545) and low MAR (<16.145) vs. high MAR (≥16.145). The primary endpoint was overall survival (OS).

RESULTS

High CD47, CD68, and CD163 expression levels were correlated with advanced clinical stage, reduced CCRT response, and elevated MLR and MAR. These TAM biomarkers were linearly correlated with each other and with established risk factors such as advanced age and elevated EBV-DNA levels. Kaplan-Meier analysis revealed that patients with low TAM expression had significantly longer OS and progression-free survival (PFS) than those with high TAM expression. Multivariate analysis identified high CD163, MLR, and MAR levels as independent adverse prognostic factors for OS. Elevated MLR is an independent risk factor for both OS and PFS in patients with NPC.

CONCLUSIONS

CD47, CD68, and CD163 are significant prognostic markers in NPC, with higher levels being associated with poorer OS and PFS. Elevated MLR and MAR values also predict worse outcomes, underscoring their value as prognostic tools. CD163 and MLR are particularly strong predictors, highlighting the crucial role of TAMs in NPC management and suggesting that CD163 is a potential therapeutic target within the immune checkpoint pathway.

摘要

背景

本研究旨在评估肿瘤相关巨噬细胞(TAM)的生物标志物CD47、CD68和CD163对鼻咽癌(NPC)治疗疗效和临床结局的预后及预测意义。此外,还评估了TAM相关指标,如单核细胞与淋巴细胞比值(MLR)和单核细胞与白蛋白比值(MAR)的预后价值。

方法

对54例接受同步放化疗(CCRT)(有或无诱导化疗)的局部晚期或寡转移NPC患者进行回顾性队列分析。根据CD47、CD68和CD163的累积表达评分将患者分为阴性/低(0 - 3分)和高(4 - 6分)两组。MLR和MAR也分别分为低MLR(<0.545)与高MLR(≥0.545)以及低MAR(<16.145)与高MAR(≥16.145)。主要终点为总生存期(OS)。

结果

CD47、CD68和CD163的高表达水平与晚期临床分期、CCRT反应降低以及MLR和MAR升高相关。这些TAM生物标志物彼此之间以及与年龄增长和EBV - DNA水平升高等既定危险因素呈线性相关。Kaplan - Meier分析显示,TAM低表达患者的OS和无进展生存期(PFS)明显长于TAM高表达患者。多因素分析确定CD163、MLR和MAR水平高是OS的独立不良预后因素。MLR升高是NPC患者OS和PFS的独立危险因素。

结论

CD47、CD68和CD163是NPC的重要预后标志物,水平越高与OS和PFS越差相关。MLR和MAR值升高也预示着更差的结局,凸显了它们作为预后工具的价值。CD163和MLR是特别强的预测指标,突出了TAM在NPC管理中的关键作用,并表明CD163是免疫检查点途径中的一个潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9a8/11639945/55bdcc2a8584/diagnostics-14-02648-g001.jpg

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