ATG5 as biomarker for early detection of malignant mesothelioma

Our plain-English summary of ATG5 as biomarker for early detection of malignant mesothelioma, by M. Tomasetti, F. Monaco, O. Strogovets, et al (BMC Research Notes, 2023).

The study

• Authors: M. Tomasetti, F. Monaco, O. Strogovets, L. Volpini, M. Valentino, M. Amati, J. Neuzil, L. Santarelli
• Journal: BMC Research Notes
• Published: 2023;16(1):61
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objectives: Malignant pleural mesothelioma (MPM) is an aggressive disease with grim prognosis due to lack of effective treatment options. Disease prediction in association with early diagnosis may both contribute to improved MPM survival. Inflammation and autophagy are two processes associated with asbestos-induced transformation. We evaluated the level of two autophagic factors ATG5 and HMGB1, microRNAs (miRNAs) such as miR-126 and miR-222, and the specific biomarker of MPM, soluble mesothelin related proteins (Mesothelin) in asbestos-exposed individuals, MPM patients, and healthy subjects. The performance of these markers in detecting MPM was investigated in pre-diagnostic samples of asbestos-subjects who developed MPM during the follow-up and compared for the three groups.

Results: The ATG5 best distinguished the asbestos-exposed subjects with and without MPM, while miR-126 and Mesothelin were found as a significant prognostic biomarker for MPM. ATG5 has been identified as an asbestos-related biomarker that can help to detect MPM with high sensitivity and specificity in pre-diagnostic samples for up to two years before diagnosis. To utilize this approach practically, higher number of cases has to be tested in order to give the combination of the two markers sufficient statistical power. Performance of the biomarkers should be confirmed by testing their combination in an independent cohort with pre-diagnostic samples.

© 2023. The Author(s).

In plain English

This Italian study measured five blood markers (ATG5, HMGB1, miR-126, miR-222 and mesothelin) as possible early signs of malignant pleural mesothelioma (MPM). The authors used 641 asbestos-exposed people recruited and periodically monitored in Ancona between November 2005 and January 2019. Seven of them developed MPM. Their blood, taken a median of 22 months before diagnosis, was compared with that of 33 other exposed people, 32 MPM patients and 16 healthy, never-exposed people. ATG5 and HMGB1 did not differ among controls, exposed people and MPM patients. Pre-diagnosis samples had higher ATG5 than exposed people and controls, and higher miR-222 than exposed people, MPM patients and controls. For separating pre-diagnosis samples from exposed people, ATG5 had an area under the curve of 0.809 (95% CI 0.65–0.97) and mesothelin 0.759 (95% CI 0.60–0.92). In epithelioid MPM patients, low miR-126 and high mesothelin were linked with significantly worse survival. The authors concluded that ATG5 can help detect MPM up to two years before diagnosis. They noted that the small number of cases limits statistical power and that confirmation in an independent cohort is needed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Biomarker study using stored blood samples from a monitored cohort of asbestos-exposed people. Pre-diagnosis samples from those who later developed MPM were compared with samples from other exposed people, MPM patients and unexposed healthy controls.
• Who was studied: Ancona, Italy. Out of 641 asbestos-exposed people recruited and monitored between November 2005 and January 2019, the study used 7 who developed MPM (pre-diagnosis samples taken a median of 22 months before diagnosis) and 33 other asbestos-exposed people. These were compared with 32 MPM patients (accepted 2008–2019) and 16 healthy controls never exposed to asbestos. Total 88; 92% male.
• Exposure: Asbestos exposure, estimated for each exposed person with a 'fiber-year' metric. The article does not name fiber types.
• Main results:
  • Serum ATG5 and HMGB1 did not differ among healthy controls, asbestos-exposed subjects and MPM patients.
  • MPM patients had low levels of miR-126 compared with asbestos-exposed subjects and controls.
  • Pre-diagnosis serum from asbestos-exposed subjects who later developed MPM had high ATG5 compared with asbestos-exposed and control subjects.
  • Pre-diagnosis samples had high miR-222 compared with the asbestos-exposed, MPM and control groups.
  • In separating pre-diagnosis samples from asbestos-exposed subjects, ATG5 had an AUC of 0.809 (95% CI, 0.65–0.97) and mesothelin an AUC of 0.759 (95% CI, 0.60–0.92).
  • High levels of ATG5, miR-222 and mesothelin were associated with benign asbestos-related diseases such as asbestosis and/or pleural plaques.
  • Among patients with epithelioid MPM, those with low miR-126 and high mesothelin levels had significantly worse overall survival.
• The authors' conclusion: The authors concluded that ATG5 is an asbestos-related biomarker that can help detect MPM with high sensitivity and specificity in pre-diagnostic samples up to two years before diagnosis.
• Limitations the authors state:
  • The number of cases was small. More cases must be tested to give the combination of markers sufficient statistical power.
  • The biomarker performance must be confirmed in an independent cohort.
  • Factors other than early MPM might affect ATG5 and miR-222 levels.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Biomarker, Mesothelioma, Pleural Mesothelioma, Prognosis, Inflammation, High Mobility Group Box 1 (HMGB1), Mesothelin.

Related studies

• Circulating epigenetic biomarkers in lung malignancies: From early diagnosis to therapy — M. Tomasetti, M. Amati, et al. (2017)
• Association of MiR-126 with soluble mesothelin-related peptides, a marker for malignant mesothelioma — L. Santarelli, E. Strafella, et al. (2011)
• Profiling tumor-associated markers for early detection of malignant mesothelioma: an epidemiologic study — M. Amati, M. Tomasetti, et al. (2008)
• Are circulating microRNAs suitable for the early detection of malignant mesothelioma? Results from a nested case-control study — D.G. Weber, A. Brik, et al. (2019)
• miR-1254 and miR-574-5p: serum-based microRNA biomarkers for early-stage non-small cell lung cancer — K.M. Foss, C. Sima, et al. (2011)
• Four-miRNA Signature to Identify Asbestos-Related Lung Malignancies — L. Santarelli, S. Gaetani, et al. (2019)

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