Pleural Homocysteine for Malignant Pleural Effusion: A Prospective and Double-blind Diagnostic Test Accuracy Study

Overview

Journal Thorac Cancer

Specialties Oncology
Pulmonary Medicine

Date 2022 Jul 11

PMID 35817406

Authors

Xi-Shan Cao

Wen Zhao

Xu-Hui Wen

Yu-Ling Han

Li Yan

Ting-Wang Jiang

Jin-Hong Huang

Hong Chen

Wen-Qi Zheng

Zhi-De Hu

Affiliations

Soon will be listed here.

Abstract

Objective: To assess the accuracy of pleural fluid homocysteine for discriminating malignant pleural effusion (MPE) and benign pleural effusion (BPE).

Methods: A total of 194 patients from two cohorts (Hohhot and Changshu) with undiagnosed pleural effusion were prospectively enrolled. Their pleural homocysteine was measured, and its diagnostic accuracy and net benefit for MPE were analyzed by receiver operating characteristic (ROC) curve analysis and decision curve analysis, respectively.

Results: In the Hohhot cohort (n = 136) and the Changshu cohort (n = 58), MPE patients had significantly higher homocysteine levels than BPE patients. The areas under the ROC curves of homocysteine for the diagnosis of MPE were 0.61 (p = 0.027) and 0.59 (p = 0.247), respectively. The decision curves of homocysteine were close to the reference line in both the Hohhot cohort and the Changshu cohort.

Conclusion: The diagnostic accuracy of pleural fluid homocysteine for MPE was low.

Citing Articles

Diagnostic Utility of Pleural C-Reactive Protein and Procalcitonin for Parapneumonic Pleural Effusion: A Head-to-Head Comparison Study.

Yang Q, Cha S, Niu Y, Wen J, Yan L, Hai L Infect Drug Resist. 2025; 18:919-927.

PMID: 39990779 PMC: 11844198. DOI: 10.2147/IDR.S493610.

Pleural pro-gastrin releasing peptide is a potential diagnostic marker for malignant pleural effusion induced by small-cell lung cancer.

Wang Y, Yang Q, Hai L, Zhou F, Zhang L, Wang Y J Thorac Dis. 2024; 16(7):4440-4446.

PMID: 39144330 PMC: 11320258. DOI: 10.21037/jtd-24-278.

Pleural carbohydrate antigen 50 and malignant pleural effusion: a prospective, double-blind diagnostic accuracy test.

Cha S, Niu Y, Wen J, Yan C, Yang Q, Zhu H Transl Lung Cancer Res. 2024; 13(5):1061-1068.

PMID: 38854948 PMC: 11157376. DOI: 10.21037/tlcr-24-68.

Value of human epididymis secretory protein 4 in differentiating malignant from benign pleural effusion: an analysis of two cohorts.

Yang Q, Niu Y, Wen J, Yang D, Han Y, Wen X Ther Adv Respir Dis. 2023; 17:17534666231216566.

PMID: 38084849 PMC: 10722922. DOI: 10.1177/17534666231216566.

Long-term stability of pleural fluid carcinoembryonic antigen and its effect on the diagnostic accuracy for malignant pleural effusion.

Yang D, Niu Y, Wen J, Wen X, Wang Y, Yan L Thorac Cancer. 2023; 14(21):2077-2084.

PMID: 37314828 PMC: 10363804. DOI: 10.1111/1759-7714.14996.

References

He T, Jin X, Koh Y, Zhang Q, Zhang C, Liu F . The association of homocysteine, folate, vitamin B12, and vitamin B6 with fracture incidence in older adults: a systematic review and meta-analysis. Ann Transl Med. 2021; 9(14):1143. PMC: 8350623. DOI: 10.21037/atm-21-2514. View

Zhang M, Yan L, Lippi G, Hu Z . Pleural biomarkers in diagnostics of malignant pleural effusion: a narrative review. Transl Lung Cancer Res. 2021; 10(3):1557-1570. PMC: 8044497. DOI: 10.21037/tlcr-20-1111. View

Kassirian S, Hinton S, Cuninghame S, Chaudhary R, Iansavitchene A, Amjadi K . Diagnostic sensitivity of pleural fluid cytology in malignant pleural effusions: systematic review and meta-analysis. Thorax. 2022; 78(1):32-40. DOI: 10.1136/thoraxjnl-2021-217959. View

Porcel J, Esquerda A, Vives M, Bielsa S . Etiology of pleural effusions: analysis of more than 3,000 consecutive thoracenteses. Arch Bronconeumol. 2013; 50(5):161-5. DOI: 10.1016/j.arbres.2013.11.007. View

Light R . Clinical practice. Pleural effusion. N Engl J Med. 2002; 346(25):1971-7. DOI: 10.1056/NEJMcp010731. View

Yang Y, Liu Y, Shi H . Diagnostic Accuracy of Combinations of Tumor Markers for Malignant Pleural Effusion: An Updated Meta-Analysis. Respiration. 2017; 94(1):62-69. DOI: 10.1159/000468545. View

Santotoribio J, Canavate-Solano C, La Torre A, Valle-Vazquez L, Arce-Matute F, Cuadros-Munoz J . Homocysteine: new tumor marker in pleural fluid. Tumour Biol. 2015; 36(10):7941-5. DOI: 10.1007/s13277-015-3517-9. View

Schernhammer E, Wolpin B, Rifai N, Cochrane B, Manson J, Ma J . Plasma folate, vitamin B6, vitamin B12, and homocysteine and pancreatic cancer risk in four large cohorts. Cancer Res. 2007; 67(11):5553-60. DOI: 10.1158/0008-5472.CAN-06-4463. View

Schlattmann P . Statistics in diagnostic medicine. Clin Chem Lab Med. 2022; 60(6):801-807. DOI: 10.1515/cclm-2022-0225. View

10.

Han L, Huang X, Wang J, Lin H, Zhang Q, Gu Y . Optimization of an enzyme-coupling method by spectrophotometer for serum adenosine deaminase: As a candidate reference method. Anal Biochem. 2019; 587:113462. DOI: 10.1016/j.ab.2019.113462. View

11.

Jakubowski H . Homocysteine Modification in Protein Structure/Function and Human Disease. Physiol Rev. 2018; 99(1):555-604. DOI: 10.1152/physrev.00003.2018. View

12.

Creaney J, Lee Y . Diagnoses (Not Diagnosis) of Pleural Effusion. Time to Consider Concurrent Etiologies. Ann Am Thorac Soc. 2016; 13(7):1003-4. DOI: 10.1513/AnnalsATS.201604-320ED. View

13.

Cao X, Zhao W, Wen X, Han Y, Yan L, Jiang T . Pleural homocysteine for malignant pleural effusion: A prospective and double-blind diagnostic test accuracy study. Thorac Cancer. 2022; 13(16):2355-2361. PMC: 9376178. DOI: 10.1111/1759-7714.14570. View

14.

Laulu S, Rawlins M, Pfeiffer C, Zhang M, Roberts W . Performance characteristics of six homocysteine assays. Am J Clin Pathol. 2008; 130(6):969-75. DOI: 10.1309/AJCP64BJIPNPSQDJ. View

15.

Bossuyt P, Reitsma J, Bruns D, Gatsonis C, Glasziou P, Irwig L . STARD 2015: An Updated List of Essential Items for Reporting Diagnostic Accuracy Studies. Clin Chem. 2015; 61(12):1446-52. DOI: 10.1373/clinchem.2015.246280. View

16.

Mocellin S, Briarava M, Pilati P . Vitamin B6 and Cancer Risk: A Field Synopsis and Meta-Analysis. J Natl Cancer Inst. 2017; 109(3):1-9. DOI: 10.1093/jnci/djw230. View

17.

Hasan T, Arora R, Bansal A, Bhattacharya R, Sharma G, Singh L . Disturbed homocysteine metabolism is associated with cancer. Exp Mol Med. 2019; 51(2):1-13. PMC: 6389897. DOI: 10.1038/s12276-019-0216-4. View

18.

Bintcliffe O, Hooper C, Rider I, Finn R, Morley A, Zahan-Evans N . Unilateral Pleural Effusions with More Than One Apparent Etiology. A Prospective Observational Study. Ann Am Thorac Soc. 2016; 13(7):1050-6. DOI: 10.1513/AnnalsATS.201601-082OC. View

19.

Haltmayer M, Mueller T, Gegenhuber A, Poelz W . Comparison of the automated AxSYM and ADVIA centaur immunoassays for homocysteine determination. Clin Lab. 2004; 50(3-4):175-80. View

20.

Wei D, Mao Q . Vitamin B6, vitamin B12 and methionine and risk of pancreatic cancer: a meta-analysis. Nutr J. 2020; 19(1):111. PMC: 7534168. DOI: 10.1186/s12937-020-00628-7. View