LOX family and ZFPM2 as novel diagnostic biomarkers for malignant pleural mesothelioma

Our plain-English summary of LOX family and ZFPM2 as novel diagnostic biomarkers for malignant pleural mesothelioma, by M.K. Kim, H.W. Kim, M. Jang, et al (Biomarker Research, 2020).

The study

• Authors: M.K. Kim, H.W. Kim, M. Jang, S.S. Oh, S.J. Yong, Y. Jeong, S.H. Jung, J.W. Choi
• Journal: Biomarker Research
• Published: 2020;8:1
• Cited by: 26 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer that develops in the pleural and outer layer of tissues surrounding the lungs. MPM is primarily caused by occupational exposure to asbestos and results in a poor prognosis. Effective therapeutics as well as early diagnostics for the MPM are still lacking. To identify potential diagnostic biomarkers for MPM, we performed bioinformatics analysis of public database.

Methods: Utilizing databases from Cancer Cell Line Encyclopedia (CCLE) and Gene Expression Omnibus (GEO), we identified several potential candidates that could act as MPM biomarkers. We carried out additional molecular analyses of these potential markers using MPM patient tissue samples via quantitative polymerase chain reaction.

Results: We identified Lysyl oxidase (LOX), Lysyl oxidase homologs 1&2 (LOXL1& LOXL2) Zinc Finger Protein, FOG Family Member 2 (ZFPM2) as potential diagnostic biomarkers for MPM. In this study, we found that the LOX family and ZFPM2 showed comparable diagnostic ability to Fibulin-3 or mesothelin (MSLN) and would be better potential biomarkers than Sulfatase 1 (SULF1), Thrombospondin 2 (THBS2) and Cadherin 11 (CDH11).

Conclusions: LOX family and ZPFM2 were identified as novel MPM diagnostic biomarkers which could strengthen MPM clinical diagnostic capabilities.

© The Author(s). 2020.

In plain English

This laboratory study from Yonsei University Wonju College of Medicine in Korea looked for genes that might help diagnose malignant pleural mesothelioma (MPM). It did not examine asbestos exposure. Using a public database, the authors compared 14 MPM and 32 lung adenocarcinoma cell lines and listed 50 genes more active in the MPM lines. They then checked candidate genes in a public dataset of 9 normal and 40 MPM tissue samples. Seven genes (LOX, LOXL1, LOXL2, ZFPM2, SULF1, THBS2 and CDH11) were significantly more active in MPM tissue. The authors reported high sensitivity and specificity for the LOX family and ZFPM2, and judged the LOX family's diagnostic power comparable to or greater than that of the known marker Fibulin-3. Finally, they measured LOX, LOXL1, LOXL2 and ZFPM2 by qPCR and reported significantly higher levels in MPM than in non-cancer samples. The figure for this test describes tissue from one non-cancer patient and one MPM patient, though the methods refer to patients in the plural. The authors concluded these four genes could be combined with previously proposed markers to strengthen MPM diagnosis.

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: Laboratory biomarker study: bioinformatic analysis of public gene-expression databases (CCLE and GEO), followed by quantitative PCR testing of patient samples, which the authors call a case-control study
• Who was studied: Database part: 14 malignant pleural mesothelioma and 32 lung adenocarcinoma cell lines (CCLE), and a public dataset of 9 normal and 40 MPM tissue samples (GEO, GSE2549). Patient part: samples collected under the ethics approval of Yonsei University Wonju College of Medicine, Republic of Korea. The Figure 3 legend describes mesothelium tissue from one non-cancer patient and one MPM patient. The methods and results instead refer to non-cancer and MPM patients in the plural and describe the samples as bronchioalveolar lavage fluid or pleural effusion. No dates are given.
• Exposure: Not studied. The article compares gene activity in malignant pleural mesothelioma with normal tissue, lung adenocarcinoma and non-cancer samples. It reports no asbestos exposure data for the cell lines or patients.
• Main results:
  • Comparing 14 MPM cell lines with 32 lung adenocarcinoma cell lines, the authors identified a signature of 50 genes with higher activity in the MPM cell lines.
  • In the public tissue dataset (9 normal, 40 MPM), the known markers Fibulin-3, MSLN (mesothelin) and CALB2 were significantly more active in MPM tissue than in normal tissue.
  • In the same tissue dataset, LOX, LOXL1, LOXL2, ZFPM2, SULF1, THBS2 and CDH11 were significantly more active in MPM tissue than in normal samples.
  • In the authors' ROC analysis of the tissue dataset, the LOX family and ZFPM2 showed high sensitivity and specificity. The authors judged the LOX family's diagnostic power comparable to or greater than that of Fibulin-3. No numerical values appear in the text.
  • In qPCR testing, LOX, LOXL1, LOXL2 and ZFPM2 were reported as significantly higher in MPM than in non-cancer samples. The figure legend describes tissue from one non-cancer patient and one MPM patient.
• The authors' conclusion: The authors concluded that the four candidates (LOX, LOXL1, LOXL2, ZFPM2) could be combined with previously proposed biomarkers to strengthen the diagnostic power for MPM patients.

Topics

Medical terms in this study, explained in our Lexicon: Biomarker, Pleural Mesothelioma, Occupational Exposure, Prognosis, Fibulin-3, Mesothelin.

Related studies

• The "don't eat me" signal CD47 is a novel diagnostic biomarker and potential therapeutic target for diffuse malignant mesothelioma — C.M. Schürch, S. Forster, et al. (2017)
• Can novel adipokines, asprosin and meteorin-like, be biomarkers for malignant mesothelioma? — N. Kocaman, G. Artaş (2020)
• Biomarkers for Malignant Pleural Mesothelioma-A Novel View on Inflammation — M. Vogl, A. Rosenmayr, et al. (2021)
• Early Contrast Enhancement: A novel magnetic resonance imaging biomarker of pleural malignancy — S. Tsim, C.A. Humphreys, et al. (2018)
• A Novel Panel of Serum Biomarkers for MPM Diagnosis — A. Bonotti, R. Foddis, et al. (2017)
• Exploration of identifying novel serum biomarkers for malignant mesothelioma using iTRAQ combined with 2D-LC-MS/MS — H. Xia, L. Feng, et al. (2021)

Browse more research in Biomarker Research, or return to medical research.