The lncRNAs Gas5, MALAT1 and SNHG8 as diagnostic biomarkers for epithelial malignant pleural mesothelioma in Egyptian patients

Our plain-English summary of The lncRNAs Gas5, MALAT1 and SNHG8 as diagnostic biomarkers for epithelial malignant pleural mesothelioma in Egyptian patients, by D.M. Elkahwagy, C.J. Kiriacos, M.E. Sobeih, et al (Scientific Reports, 2024).

The study

• Authors: D.M. Elkahwagy, C.J. Kiriacos, M.E. Sobeih, O.M.R. Khorshid, M. Mansour
• Journal: Scientific Reports
• Published: 2024;14(1):4823
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Long noncoding RNAs have been shown to be involved in a myriad of physiological and pathological pathways. To date, malignant pleural mesothelioma (MPM) is considered an extremely aggressive cancer. One reason for this is the late diagnosis of the disease, which can occur within 30-40 years of asbestos exposure. There is an immense need for the development of new, sensitive, inexpensive and easy methods for the early detection of this disease other than invasive methods such as biopsy. The aim of this study was to determine the expression of circulating lncRNAs in mesothelioma patient plasma to identify potential biomarkers. Ten previously identified lncRNAs that were shown to be aberrantly expressed in mesothelioma tissues were selected as candidates for subsequent validation. The expression of the ten selected candidate lncRNAs was verified via quantitative PCR (qPCR) in human plasma samples from mesothelioma patients versus healthy controls. The expression levels of circulating GAS5, SNHG8 and MALAT1 were significantly greater in plasma samples from patients than in those from controls. The ROC analysis of both MALAT1 and SNHG8 revealed 88.89% sensitivity and 66.67% specificity. The sensitivity of these markers was greater than that of GAS5 (sensitivity 72.22% and specificity 66.67%). The regression model for GAS5 was statistically significant, while that for SNHG8 and MALAT1 was not significant due to the small sample size. The area under the curve (AUC) of the three ROC curves was acceptable and significant: 0.7519 for GAS5, 0.7352 for SNHG8 and 0.7185 for MALAT1. This finding confirmed their ability to be used as markers. The three lncRNAs were not affected by age, sex or smoking status. The three lncRNAs showed great potential as independent predictive diagnostic biomarkers. Although the prediction model for MALAT1 did not significantly differ, MALAT1 was significantly expressed in patients more than in controls (p = 0.0266), and the recorded sensitivity and specificity were greater than those of GAS5.

© 2024. The Author(s).

In plain English

This Egyptian study compared plasma from 18 newly diagnosed, untreated patients with epithelioid malignant pleural mesothelioma at Cairo's National Cancer Institute with plasma from 15 healthy controls. It tested whether ten long noncoding RNAs (lncRNAs), picked from earlier research, could serve as diagnostic markers. The article did not report participants' asbestos exposure. Only three lncRNAs, GAS5, SNHG8 and MALAT1, were detected in all samples. Levels of all three were higher in patients than controls (p values 0.013, 0.021 and 0.032). Areas under the curve for telling patients from controls were 0.7519 for GAS5 (95% confidence interval 0.586 to 0.917), 0.735 for SNHG8 (0.540 to 0.930) and 0.719 for MALAT1 (0.528 to 0.909). Sensitivity was 72.22% for GAS5 and 88.89% for the other two, with 66.67% specificity for each. The authors reported that levels were not affected by age, sex or smoking. The article was inconsistent about which logistic regression results were significant. The authors concluded that the three showed potential for distinguishing patients from controls but need validation in a larger sample, and that their use for early detection remains to be explored.

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: Diagnostic biomarker study comparing plasma from mesothelioma patients with plasma from healthy controls, measured by quantitative PCR
• Who was studied: 18 newly diagnosed, untreated patients with epithelioid malignant pleural mesothelioma from the National Cancer Institute (Cairo), recruited April 2022 to January 2023, and 15 healthy controls with no history of malignancy, drawn from outpatient clinics or patients' relatives. Mean age was 61.78 in patients and 63.87 in controls. 12 of 18 patients and 10 of 15 controls were male.
• Exposure: No asbestos exposure data for participants were reported. The study measured plasma levels of ten candidate lncRNAs (GAS5, MALAT1, PCAT6, PVT1, H19, ZFAS1, SNHG8, CASC2, POT1-AS1 and LINC00689).
• Main results:
  • Only GAS5, SNHG8 and MALAT1 were detected in the plasma of all patients and controls. The other seven lncRNAs were not stably expressed or not detectable.
  • GAS5 levels differed significantly between patients and controls (p = 0.013, 95% confidence interval 0.3718 to 2.918).
  • SNHG8 and MALAT1 levels differed significantly between patients and controls (p = 0.021 and p = 0.032, respectively).
  • Relative quantification (RQ) values were: MALAT1, 7.16 in patients and 2.04 in controls; GAS5, 3.44 in patients and 1.80 in controls; SNHG8, 3.07 in patients and 2.21 in controls.
  • GAS5 in distinguishing patients from controls: AUC 0.7519 (p = 0.014, 95% CI 0.586 to 0.917), sensitivity 72.22%, specificity 66.67%.
  • SNHG8 in distinguishing patients from controls: AUC 0.735 (p = 0.022, 95% CI 0.540 to 0.930), sensitivity 88.89%, specificity 66.67%.
  • MALAT1 in distinguishing patients from controls: AUC 0.719 (p = 0.033, 95% CI 0.528 to 0.909), sensitivity 88.89%, specificity 66.67%.
  • Levels of the three lncRNAs were not affected by age, sex or smoking status.
  • In univariate logistic regression, the odds ratio was 1.61 for GAS5 and 1.13 for MALAT1.
  • According to the Results section, SNHG8 was not statistically significant in logistic regression (odds ratio 1.81). The authors attributed this to variability between patients and reported that excluding one outlier gave significance (data not shown).
• The authors' conclusion: The authors concluded that GAS5, SNHG8 and MALAT1 showed dysregulation and potential for discriminating between patients and controls. They added that results need validation in a larger sample and that use for early detection remains to be explored.
• Limitations the authors state:
  • The results need to be validated in a larger sample.
  • Combinations of lncRNAs were tested, but the results were not significant because of the limited sample size (data not shown).
  • Patients were recently diagnosed but at late stages of tumor development. Prediagnostic samples were not used.
  • For MALAT1, a larger sample including other covariates that may influence its expression is needed.
  • The extraction kit may not have captured all forms of circulating lncRNA, which may explain why seven lncRNAs were not detected.

Topics

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

Medical terms in this study, explained in our Lexicon: Biomarker, Pleural Mesothelioma, Asbestos Exposure, Biopsy, Mesothelioma.

Related studies

• Long non coding RNAs (lncRNAs) are dysregulated in Malignant Pleural Mesothelioma (MPM) — C.M. Wright, M.B. Kirschner, et al. (2013)
• Clinical significance of serum DRAM1 mRNA, ARSA mRNA, hsa-miR-2053 and lncRNA-RP1-86D1.3 axis expression in malignant pleural mesothelioma — M. Matboli, A.E. Shafei, et al. (2019)
• GAS5 long non-coding RNA in malignant pleural mesothelioma — A. Renganathan, J. Kresoja-Rakic, et al. (2014)
• Usage of personal protective devices among Egyptian industrial workers — A.A. Kamal, G.M. Sayed, et al. (1988)
• Evaluation of simian virus-40 as a biological prognostic factor in Egyptian patients with malignant pleural mesothelioma — A.R. Zekri, A.A. Bahnassy, et al. (2007)
• BAP1 gene mutations in Egyptian patients with advanced sporadic malignant pleural mesothelioma (MPM): relation with clinical outcomes and survival — A.A. Bahnasy, R.S. El-Din, et al. (2018)

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