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MicroRNA Based Liquid Biopsy: The Experience of the Plasma miRNA Signature Classifier MSC for Lung Cancer Screening
Published on: October 26, 2017
Mediation of association between benzo[a]pyrene exposure and lung cancer risk by plasma microRNAs: A Chinese
Yang Xiao1, Chenliang Liu1, Ye Fu1
1Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Abstract:
Epidemiologic studies have reported the positive relationship of benzo[a]pyrene (BaP) exposure with the risk of lung cancer. However, the mechanisms underlying the relationship is still unclear. Plasma microRNA (miRNA) is a typical epigenetic biomarker that was linked to environment exposure and lung cancer development. We aimed to reveal the mediation effect of plasma miRNAs on BaP-related lung cancer. We designed a lung cancer case-control study including 136 lung cancer patients and 136 controls, and measured the adducts of benzo[a]pyrene diol epoxide-albumin (BPDE-Alb) and sequenced miRNA profiles in plasma. The relationships between BPDE-Alb adducts, normalized miRNA levels and the risk of lung cancer were assessed by linear regression models. The mediation effects of miRNAs on BaP-related lung cancer were investigated. A total of 190 plasma miRNAs were significantly related to lung cancer status at Bonferroni adjusted P < 0.05, among which 57 miRNAs showed different levels with |fold change| > 2 between plasma samples before and after tumor resection surgery at Bonferroni adjusted P < 0.05. Especially, among the 57 lung cancer-associated miRNAs, BPDE-Alb adducts were significantly related to miR-17-3p, miR-20a-3p, miR-135a-5p, miR-374a-5p, miR-374b-5p, miR-423-5p and miR-664a-5p, which could in turn mediate a separate 42.2%, 33.0%, 57.5%, 36.4%, 48.8%, 32.5% and 38.2% of the relationship of BPDE-Alb adducts with the risk of lung cancer. Our results provide non-invasion biomarker candidates for lung cancer, and highlight miRNAs dysregulation as a potential intermediate mechanism by which BaP exposure lead to lung tumorigenesis.
Insights
Benzo[a]pyrene (BaP) exposure increases lung cancer risk. Plasma microRNAs (miRNAs) may mediate this link, offering potential non-invasive biomarkers for early lung cancer detection and understanding BaP
Area of Science:
- Environmental Health
- Molecular Biology
- Cancer Research
Background:
- Epidemiologic studies link benzo[a]pyrene (BaP) exposure to increased lung cancer risk.
- The precise mechanisms connecting BaP exposure to lung tumorigenesis remain unclear.
- Plasma microRNAs (miRNAs) are emerging epigenetic biomarkers associated with environmental exposures and cancer development.
Purpose of the Study:
- To investigate the mediating role of plasma microRNAs (miRNAs) in the relationship between BaP exposure and lung cancer.
- To identify potential non-invasive miRNA biomarkers for BaP-related lung cancer.
Main Methods:
- A lung cancer case-control study involving 136 patients and 136 controls.
- Measurement of benzo[a]pyrene diol epoxide-albumin (BPDE-Alb) adducts as a biomarker of BaP exposure.
- Sequencing of plasma miRNA profiles and assessment of relationships using linear regression models and mediation analysis.
Main Results:
- 190 plasma miRNAs were significantly associated with lung cancer status.
- 57 miRNAs showed differential expression levels before and after tumor resection.
- Specific miRNAs (e.g., miR-17-3p, miR-135a-5p) were linked to BPDE-Alb adducts and mediated a significant portion of the BaP-lung cancer relationship (e.g., 42.2% and 57.5%, respectively).
Conclusions:
- Plasma miRNAs may act as intermediate mechanisms in BaP-induced lung tumorigenesis.
- Dysregulation of specific miRNAs is highlighted as a potential pathway linking BaP exposure to lung cancer.
- Identified miRNAs represent promising non-invasive biomarker candidates for lung cancer risk assessment.
