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肺转移性癌的血浆代谢组学研究

Plasm Metabolomics Study in Pulmonary Metastatic Carcinoma.

作者信息

Liu Zixu, Wang Ling, Du Minjun, Liang Yicheng, Liang Mei, Li Zhili, Gao Yushun

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, Beijing, China.

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

出版信息

J Oncol. 2022 Aug 21;2022:9460019. doi: 10.1155/2022/9460019. eCollection 2022.

Abstract

BACKGROUND

The lung is one of the most common metastatic sites of malignant tumors. Early detection of pulmonary metastatic carcinoma can effectively reduce relative cancer mortality. Human metabolomics is a qualitative and quantitative study of low-molecular metabolites in the body. By studying the plasm metabolomics of patients with pulmonary metastatic carcinoma or other lung diseases, we can find the difference in plasm levels of low-molecular metabolites among them. These metabolites have the potential to become biomarkers of lung metastases.

METHODS

Patients with pulmonary nodules admitted to our department from February 1, 2019, to May 31, 2019, were collected. According to the postoperative pathological results, they were divided into three groups: pulmonary metastatic carcinoma (PMC), benign pulmonary nodules (BPN), and primary lung cancer (PLC). Moreover, healthy people who underwent physical examination were enrolled as the healthy population group (HPG) during the same period. On the one hand, to study lung metastases screening in healthy people, PMC was compared with HPG. The multivariate statistical analysis method was used to find the significant low-molecular metabolites between the two groups, and their discriminating ability was verified by the ROC curve. On the other hand, from the perspective of differential diagnosis of lung metastases, three groups with different pulmonary lesions (PMC, BPN, and PLC) were compared as a whole, and then the other two groups were compared with PMC, respectively. The main low-molecular metabolites were selected, and their discriminating ability was verified.

RESULTS

In terms of lung metastases screening for healthy people, four significant low-molecular metabolites were found by comparison of PMC and HPG. They were O-arachidonoyl ethanolamine, adrenoyl ethanolamide, tricin 7-diglucuronoside, and p-coumaroyl vitisin A. In terms of the differential diagnosis of pulmonary nodules, the significant low-molecular metabolites selected by the comparison of the three groups as a whole were anabasine, octanoylcarnitine, 2-methoxyestrone, retinol, decanoylcarnitine, calcitroic acid, glycogen, and austalide L. For the comparison of PMC and BPN, L-tyrosine, indoleacrylic acid, and lysoPC (16 : 0) were selected, while L-octanoylcarnitine, retinol, and decanoylcarnitine were selected for the comparison of PMC and PLC. Their AUCs of ROC are all greater than 0.80. It indicates that these substances have a strong ability to differentiate between pulmonary metastatic carcinoma and other pulmonary nodule lesions.

CONCLUSION

Through the research of plasm metabolomics, it is possible to effectively detect the changes in some low-molecular metabolites among primary lung cancer, pulmonary metastatic carcinoma, and benign pulmonary nodule patients and healthy people. These significant metabolites have the potential to be biomarkers for screening and differential diagnosis of lung metastases.

摘要

背景

肺是恶性肿瘤最常见的转移部位之一。早期发现肺转移性癌可有效降低癌症相对死亡率。人类代谢组学是对体内低分子代谢物进行定性和定量研究。通过研究肺转移性癌患者或其他肺部疾病患者的血浆代谢组学,我们可以发现他们之间低分子代谢物血浆水平的差异。这些代谢物有可能成为肺转移的生物标志物。

方法

收集2019年2月1日至2019年5月31日入住我科的肺结节患者。根据术后病理结果,将他们分为三组:肺转移性癌(PMC)、良性肺结节(BPN)和原发性肺癌(PLC)。此外,将同期接受体检的健康人纳入健康人群组(HPG)。一方面,为研究健康人群中的肺转移筛查,将PMC与HPG进行比较。采用多元统计分析方法找出两组之间显著的低分子代谢物,并通过ROC曲线验证其鉴别能力。另一方面,从肺转移的鉴别诊断角度,将具有不同肺部病变的三组(PMC、BPN和PLC)作为一个整体进行比较,然后分别将另外两组与PMC进行比较。选择主要的低分子代谢物,并验证其鉴别能力。

结果

在健康人群的肺转移筛查方面,通过比较PMC和HPG发现了四种显著的低分子代谢物。它们是O-花生四烯酰乙醇胺、肾上腺酰乙醇酰胺、小麦黄素7-二葡萄糖醛酸苷和对香豆酰葡萄素A。在肺结节的鉴别诊断方面,三组整体比较选择的显著低分子代谢物是新烟草碱、辛酰肉碱、2-甲氧基雌酮、视黄醇、癸酰肉碱、骨化三醇、糖原和奥司他韦L。在PMC和BPN的比较中,选择了L-酪氨酸、吲哚丙烯酸和溶血磷脂酰胆碱(16∶0),而在PMC和PLC的比较中选择了L-辛酰肉碱、视黄醇和癸酰肉碱。它们的ROC曲线下面积(AUC)均大于0.80。这表明这些物质具有很强的区分肺转移性癌和其他肺结节病变的能力。

结论

通过血浆代谢组学研究,有可能有效检测原发性肺癌、肺转移性癌、良性肺结节患者及健康人之间一些低分子代谢物的变化。这些显著的代谢物有可能成为肺转移筛查和鉴别诊断的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34d3/9420632/e1c354a0b794/JO2022-9460019.001.jpg

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