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血浆代谢组学在多原发肺癌筛查和鉴别诊断中的研究。

Plasma metabolomics study in screening and differential diagnosis of multiple primary lung cancer.

机构信息

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College.

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Hebei Cancer Hospital, Langfang, People's Republic of China.

出版信息

Int J Surg. 2023 Mar 1;109(3):297-312. doi: 10.1097/JS9.0000000000000006.

Abstract

BACKGROUND

Multiple primary lung cancer (MPLC) is becoming increasingly common in clinical practice. Imaging examination is sometimes difficult to differentiate from intrapulmonary metastasis (IM) or single primary lung cancer (SPLC) before surgery. There is a lack of effective blood biomarkers as an auxiliary diagnostic method.

PARTICIPANTS AND METHODS

A total of 179 patients who were hospitalized and operated in our department from January to June 2019 were collected, and they were divided into SPLC with 136 patients, MPLC with 24 patients, and IM with 19 patients. In total, 96 healthy people without lung cancer were enrolled. Medical history, imaging, and pathology data were assembled from all participants. Plasma metabolomics analysis was performed by quadrupole time-of-flight tandem mass spectrometry, and data were analyzed using SPSS19.0/Simca 14.1/MetaboAnalyst5.0 software. Significant metabolites were selected by variable importance in projection, P value, and fold change. The area under the receiver operating characteristic curve was used to evaluate their diagnostic ability.

RESULTS

There were significant differences in plasma metabolite profiles between IM and MPLC. Seven metabolites were screened out. Two metabolites had higher levels in IM, and five metabolites had higher levels in MPLC. All had favorable discriminating capacity. Phosphatidyl ethanolamine (38:5) showed the highest sensitivity (0.95) and specificity (0.92). It was followed by l -histidine with sensitivity 0.92 and specificity 0.84. l -tyrosine can be used to identify SPLC and MPLC. The panel composed of related metabolites exhibited higher diagnostic ability. Eight principal metabolites caused remarkable differences between healthy people and MPLC, and five of them had area under the curves greater than 0.85, showing good discriminating power.

CONCLUSION

Through the study of plasma metabolomics, it was found that there were obvious differences in the metabolite profiles of MPLC, IM, SPLC, and the healthy population. Some discovered metabolites possessed excellent diagnostic competence with high sensitivity and specificity. They had the potential to act as biomarkers for the screening and differential diagnosis of MPLCs.

摘要

背景

多原发肺癌(MPLC)在临床实践中越来越常见。在手术前,影像学检查有时难以将其与肺内转移(IM)或单发原发性肺癌(SPLC)区分开来。目前缺乏有效的血液生物标志物作为辅助诊断方法。

参与者和方法

共收集 2019 年 1 月至 6 月在我科住院并接受手术的 179 例患者,其中 SPLC 患者 136 例,MPLC 患者 24 例,IM 患者 19 例。同时纳入 96 例无肺癌的健康人。收集所有参与者的病史、影像学和病理学资料。采用四极杆飞行时间串联质谱法进行血浆代谢组学分析,使用 SPSS19.0/Simca 14.1/MetaboAnalyst5.0 软件进行数据分析。采用变量重要性投影(VIP)值、P 值和倍数变化筛选有统计学意义的代谢物。采用受试者工作特征曲线下面积(AUC)评价其诊断效能。

结果

IM 与 MPLC 患者的血浆代谢物谱存在显著差异。筛选出 7 种差异代谢物。2 种代谢物在 IM 中水平较高,5 种代谢物在 MPLC 中水平较高,均具有良好的区分能力。其中,磷酸乙醇胺(38:5)的敏感性(0.95)和特异性(0.92)最高,其次是 l-组氨酸,敏感性为 0.92,特异性为 0.84。l-酪氨酸可用于鉴别 SPLC 和 MPLC。由相关代谢物组成的panel 具有更高的诊断效能。8 种主要代谢物导致健康人与 MPLC 之间的差异显著,其中 5 种代谢物的曲线下面积(AUC)大于 0.85,具有良好的区分能力。

结论

通过血浆代谢组学研究发现,MPLC、IM、SPLC 和健康人群的代谢物谱存在明显差异。部分发现的代谢物具有较高的敏感性和特异性,诊断效能良好,具有作为 MPLC 筛查和鉴别诊断生物标志物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b982/10389222/37a7461bc7ef/js9-109-297-g001.jpg

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