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血浆 versican 和血浆外泌体 versican 作为非小细胞肺癌的潜在诊断标志物。

Plasma versican and plasma exosomal versican as potential diagnostic markers for non-small cell lung cancer.

机构信息

Department of Laboratory Medicine, Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, China.

Department of Laboratory Medicine, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou Normal University, Huzhou, 313003, China.

出版信息

Respir Res. 2023 May 31;24(1):140. doi: 10.1186/s12931-023-02423-4.

Abstract

BACKGROUND AND AIMS

This study aimed to investigate the expression of plasma versican and plasma exosomal versican in non-small cell lung cancer (NSCLC) and its correlation with clinicopathological features, and to evaluate its diagnostic performance in NSCLC and its predictive function for NSCLC incidence and metastasis risk.

MATERIALS AND METHODS

There were 110 instances of NSCLC, 42 cases of benign lung disease, and 55 healthy controls from September 2018 to October 2020 at Tongji Hospital Affiliated to Tongji University. Blood was collected and plasma was separated before surgery, and plasma exosomes were extracted by ExoQuick kit. Morphological and molecular phenotype identification of exosomes was performed by transmission electron microscopy, Nanosight particle tracking analysis, and western blotting. Plasma versican and plasma exosomal versican were detected in all subjects to assess their expression levels and diagnostic value in NSCLC. Clinicopathological data were collected to explore correlations between abnormal plasma versican and plasma exosomal versican expression and clinicopathological parameters. Receiver operating characteristic (ROC) curve was used to judge its diagnostic performance in NSCLC, and binary logistic regression analysis was used to predict the risk of NSCLC incidence and metastasis.

RESULTS

Plasma versican and plasma exosomal versican expression in NSCLC patients was significantly upregulated and was significantly higher in T3 + T4 patients compared with T1 + T2 patients (P < 0.05); the levels of plasma versican and plasma exosomal versican were positively correlated with lymph node metastasis, distant metastases (e.g., brain, bone), and mutation(e.g., EGFR,ALK)in NSCLC patients (all P < 0.05). Furthermore, ROC curve analysis showed that plasma versican and plasma exosomal versican had higher AUC values than NSE, CYFRA21-1, and SCC, and better diagnostic performance in NSCLC patients. However, the AUC and diagnostic performances of plasma versican and plasma exosomal versican in advanced-stage NSCLC patients were not shown to be significantly better than CEA. The results of binary logistic regression analysis showed that high levels of plasma exosomal versican had higher predictive value for lung cancer incidence, while high levels of plasma versican had higher predictive value for lung cancer metastasis.

CONCLUSION

Our findings showed that plasma versican and plasma exosomal versican might be potential diagnostic markers for NSCLC. High plasma exosomal versican expression can be used as a predictor of NSCLC risk and high plasma versican expression can be used as a predictor of NSCLC metastasis risk.

摘要

背景与目的

本研究旨在探讨非小细胞肺癌(NSCLC)患者血浆 versican 和血浆外泌体 versican 的表达及其与临床病理特征的相关性,并评估其在 NSCLC 中的诊断性能及其对 NSCLC 发病和转移风险的预测功能。

材料与方法

收集 2018 年 9 月至 2020 年 10 月同济大学附属同济医院 NSCLC 患者 110 例、良性肺部疾病患者 42 例和健康对照者 55 例,手术前采集血液并分离血浆,采用 ExoQuick 试剂盒提取血浆外泌体。通过透射电子显微镜、纳米粒子跟踪分析和 Western blot 对 exosomes 的形态和分子表型进行鉴定。检测所有受试者的血浆 versican 和血浆外泌体 versican,评估其在 NSCLC 中的表达水平及诊断价值。收集临床病理资料,探讨异常血浆 versican 和血浆外泌体 versican 表达与临床病理参数的相关性。采用受试者工作特征(ROC)曲线判断其在 NSCLC 中的诊断性能,采用二元逻辑回归分析预测 NSCLC 发病和转移风险。

结果

与 T1+T2 期患者相比,T3+T4 期 NSCLC 患者的血浆 versican 和血浆外泌体 versican 表达显著上调,且表达水平更高(P<0.05);血浆 versican 和血浆外泌体 versican 的水平与 NSCLC 患者的淋巴结转移、远处转移(如脑、骨)和突变(如 EGFR、ALK)呈正相关(均 P<0.05)。此外,ROC 曲线分析表明,血浆 versican 和血浆外泌体 versican 的 AUC 值均高于 NSE、CYFRA21-1 和 SCC,对 NSCLC 患者具有更好的诊断性能。然而,晚期 NSCLC 患者血浆 versican 和血浆外泌体 versican 的 AUC 值和诊断性能并未显示出明显优于 CEA。二元逻辑回归分析结果表明,高水平的血浆外泌体 versican 对肺癌发病具有更高的预测价值,而高水平的血浆 versican 对肺癌转移具有更高的预测价值。

结论

本研究结果表明,血浆 versican 和血浆外泌体 versican 可能是 NSCLC 的潜在诊断标志物。高血浆外泌体 versican 表达可作为 NSCLC 风险的预测指标,高血浆 versican 表达可作为 NSCLC 转移风险的预测指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3614/10230736/0b3b24fed094/12931_2023_2423_Fig1_HTML.jpg

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