CXCR4 在肺癌发生中的表达：基于早期非小细胞肺癌患者 CXCR4 表达评估生存结局的性别特异性差异。

CXCR4 expression in lung carcinogenesis: Evaluating gender-specific differences in survival outcomes based on CXCR4 expression in early stage non-small cell lung cancer patients.

机构信息

Tom Baker Cancer Centre, Calgary, Alberta, Canada.

Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

出版信息

PLoS One. 2021 Jan 28;16(1):e0241240. doi: 10.1371/journal.pone.0241240. eCollection 2021.

DOI:10.1371/journal.pone.0241240

PMID:33507926

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7842928/

Abstract

INTRODUCTION

Evidence suggests that the expression of certain cytokine receptors increases with lung cancer evolution. Overexpression of the cytokine receptor CXCR4 is associated with poor outcomes in stage IV non-small cell lung cancer (NSCLC), with shorter survival in females with high CXCR4 expression. This study quantifies CXCR4 expression in early stage disease and evaluates its association with gender-specific recurrence-free (RFS) and overall survival (OS) in resected stage I-III NSCLC patients.

METHODS

Patient characteristics and clinical outcomes were obtained from the Glans-Look Lung Cancer (G-LLC) database for early stage NSCLC patients diagnosed between 2003-2006 at the Tom Baker Cancer Centre (TBCC). CXCR4 expression was quantified on tissue microarrays (TMA). Median RFS and OS were evaluated by gender using Kaplan-Meier analyses. CXCR4 expression and outcome data were analyzed using Cox proportional hazards (PH) and multi-state models (MSM).

RESULTS

176 stage I-III NSCLC patients were identified. CXCR4 expression was lower in early stage NSCLC patients, with a mean CXCR4 expression of 1729 (SD 1083) compared to 2640 (SD 1541) in stage IV patients. On Kaplan-Meier, median RFS by gender was similar (male 52.8 months vs. female 54.5 months) as was median OS (male 80.9 months vs. female 89.0 months), and there was no significant difference in RFS (p = 0.60) or OS (p = 0.30) by gender and CXCR4 groups over follow-up. By multivariable analysis, CXCR4 expression was not prognostic for RFS (Hazard Ratio (HR) = 1.00, p = 0.73) or OS (HR = 1.00, p = 0.44), and no gender difference was observed.

CONCLUSIONS

CXCR4 expression increases with stage progression in NSCLC but is not prognostic in early stage NSCLC patients of either gender. Mechanisms by which CXCR4 expression increases during lung carcinogenesis warrant further exploration and testing in clinical trials.

摘要

简介

有证据表明，某些细胞因子受体的表达随着肺癌的发展而增加。细胞因子受体 CXCR4 的过度表达与 IV 期非小细胞肺癌（NSCLC）的不良预后相关，高 CXCR4 表达的女性患者的生存期更短。本研究定量检测了早期疾病中的 CXCR4 表达，并评估了其与接受手术治疗的 I-III 期 NSCLC 患者的性别特异性无复发生存（RFS）和总生存（OS）的相关性。

方法

从 2003 年至 2006 年在汤姆贝克癌症中心（TBCC）诊断的早期 NSCLC 患者的 Glans-Look 肺癌（G-LLC）数据库中获取患者特征和临床结局数据。使用组织微阵列（TMA）定量检测 CXCR4 表达。通过 Kaplan-Meier 分析按性别评估中位 RFS 和 OS。使用 Cox 比例风险（PH）和多状态模型（MSM）分析 CXCR4 表达和结局数据。

结果

确定了 176 例 I-III 期 NSCLC 患者。早期 NSCLC 患者的 CXCR4 表达较低，平均 CXCR4 表达为 1729（SD 1083），而 IV 期患者为 2640（SD 1541）。在 Kaplan-Meier 分析中，男性和女性的中位 RFS 相似（男性为 52.8 个月，女性为 54.5 个月），中位 OS 也相似（男性为 80.9 个月，女性为 89.0 个月），且在随访期间，RFS（p = 0.60）或 OS（p = 0.30）在性别和 CXCR4 组之间均无显著差异。多变量分析显示，CXCR4 表达与 RFS 无关（风险比（HR）= 1.00，p = 0.73）或 OS 无关（HR = 1.00，p = 0.44），且未观察到性别差异。