Exhaled breath and urinary volatile organic compounds (VOCs) for cancer diagnoses - A systematic review and meta-analysis

Sep 21, 2026

Gradual advances in detecting and quantifying volatile organic compounds (VOCs) support their use in cancer diagnosis. This systematic review and meta-analysis evaluates the diagnostic potential of exhaled breath and urinary VOCs for cancer detection and examines metabolic pathways linked to tumor development. PubMed-based searches included controlled studies, with bivariate modeling for sensitivity and specificity and clinical likelihood estimation using Fagan’s nomogram. MetOrigin was used for pathway analysis across human and microbiota contexts.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Background

Materials and Methods

Results

Conclusions

Keywords

’Systematic review and/or Meta-analysis Exhaled breath and urinary volatile organic compounds (VOCs) for cancer diagnoses, and microbial-related VOC metabolic pathway analysis: a systematic review and meta-analysis Min Zhou, MMa , Qinghua Wang, BS Medb , Xinyi Lu, BS Meda , Ping Zhang, MMa , Rui Yang, MD, PhDb , Yu Chen, MMb,* , Jiazeng Xia, MD, PhDc,* , Daozhen Chen, MD, PhDa,b,* Background: The gradual evolution of the detection and quantiﬁcation of volatile organic compounds (VOCs) has been instrumental in cancer diagnosis. The primary objective of this study was to assess the diagnostic potential of exhaled breath and urinary VOCs in cancer detection. As VOCs are indicative of tumor and human metabolism, our work also sought to investigate the metabolic pathways linked to the development of cancerous tumors. Materials and Methods: An electronic search was performed in the PubMed database. Original studies on VOCs within exhaled breath and urine for cancer detection with a control group were included. A meta-analysis was conducted using a bivariate model to assess the sensitivity and speciﬁcity of the VOCs for cancer detection. Fagan ’s nomogram was designed to leverage the ﬁndings from our diagnostic analysis for the purpose of estimating the likelihood of cancer in patients. Ultimately, MetOrigin was employed to conduct an analysis of the metabolic pathways associated with VOCs in relation to both human and/or microbiota. Results: The pooled sensitivity, speciﬁcity and the area under the curve for cancer screening utilizing exhaled breath and urinary VOCs were determined to be 0 .89, 0 .88, and 0 .95, respectively. A pretest probability of 51% can be considered as the threshold for diagnosing cancers with VOCs. As the estimated pretest probability of cancer exceeds 51%, it becomes more appropriate to emphasize the ‘ruling in’approach. Conversely, when the estimated pretest probability of cancer falls below 51%, it is more suitable to emphasize the ‘ruling out ’ approach. A total of 14, 14, 6, and 7 microbiota-related VOCs were identiﬁed in relation to lung, colorectal, breast, and liver cancers, respectively. The enrichment analysis of volatile metabolites revealed a signiﬁcant enrichment of butanoate metabolism in the aforementioned tumor types. Conclusions: The analysis of exhaled breath and urinary VOCs showed promise for cancer screening. In addition, the enrichment analysis of volatile metabolites revealed a signiﬁcant enrichment of butanoate metabolism in four tumor types, namely lung, colorectum, breast and liver. These ﬁndings hold signiﬁcant implications for the prospective clinical application of multiomics correlation in disease management and the exploration of potential therapeutic targets. Keywords: cancer, diagnosis, electronic nose, microbiota, pathway analysis, volatile organic compounds aDepartment of Breast Surgery, The Afﬁliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi Maternity and Child Health Care Hospital, bResearch Institute for Reproductive Health and Genetic Diseases, Women ’s Hospital of Jiangnan University and cDepartment of General Surgery and Translational Medicine Center, The Afﬁliated Wuxi No. 2 People ’s Hospital of Nanjing Medical University, Jiangnan University Medical Center, Wuxi, People ’s Republic of China M.Z., Q.W., and X.L. contributed equally to this work. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. *Corresponding authors. Address: Department of Breast Surgery, The Afﬁliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi Maternity and Child Health Care Hospital, No. 48 Huaishu Rd, Wuxi, People’s Republic of China. fax: +[86 0510 82726068. E-mail: chendaozhen@163.com](86 0510 82726068. E-mail: chendaozhen@163.com) (D. Chen); Department of General Surgery and Translational Medicine Center, The Afﬁliated Wuxi No. 2

FAQs

What diagnostic data does the study evaluate for cancer detection?

The study assesses VOCs measured in exhaled breath and urine for cancer detection, using included controlled studies and meta-analytic methods.

How were diagnostic performance metrics analyzed in the review?

A bivariate model estimated sensitivity and specificity, and the area under the curve (AUC) was computed for cancer screening using exhaled breath and urinary VOCs.

What microbiota- and metabolism-related findings were reported?

Four cancer types showed enrichment of butanoate metabolism, and the review identified multiple microbiota-related VOCs associated with lung, colorectal, breast, and liver cancers.

Sep 21, 2026

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