Sera from Patients with Malignant Pleural Mesothelioma Tested Positive for IgG Antibodies against SV40 Large T Antigen: The Viral Oncoprotein

Our plain-English summary of Sera from Patients with Malignant Pleural Mesothelioma Tested Positive for IgG Antibodies against SV40 Large T Antigen: The Viral Oncoprotein, by E. Mazzoni, I. Bononi, J.C. Rotondo, et al (Journal of Oncology, 2022).

The study

• Authors: E. Mazzoni, I. Bononi, J.C. Rotondo, C. Mazziotta, R. Libener, R. Guaschino, R. Gafà, G. Lanza, F. Martini, M. Tognon
• Journal: Journal of Oncology
• Published: 2022;2022:7249912
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM), a fatal tumor, is mainly linked to the asbestos exposure. It has been reported that together with the inhalation of asbestos fibers, other factors are involved in the MPM onset, including simian virus 40 (SV40). SV40, a polyomavirus with oncogenic potential, induces (i) in vitro the mesenchymal cell transformation, whereas (ii) in vivo the MPM onset in experimental animals. The association between MPM and SV40 in humans remains to be elucidated. Sera (n = 415) from MPM-affected patients (MPM cohort 1; n = 152) and healthy subjects (HSs, n = 263) were investigated for their immunoglobulin G (IgG) against simian virus 40 large tumor antigen (Tag), which is the transforming protein. Sera were investigated with an indirect enzyme-linked immunosorbent assay (ELISA) using two synthetic peptides from SV40 Tag protein. SV40 Tag protein was evaluated by immunohistochemical (IHC) staining on MPM samples (MPM cohort 2; n = 20). Formalin-fixed and paraffin-embedded (FFPE) samples were obtained from MPM patients unrelated to MPM serum donors. The proportion of sera, from MPM patients, showing antibodies against SV40 Tag (34%) was significantly higher compared to HSs (20%) (odds ratio 2.049, CI 95% 1.32-3.224; p=0.0026). Immunohistochemical staining (IHS) assays showed SV40 Tag expression in 8/20, 40% of MPM specimens. These results indicate that SV40 is linked to a large fraction of MPM. It is worth noting that the prevalence of SV40 Tag antibodies detected in sera from cohort 1 of MPM patients is similar to the prevalence of SV40 Tag found to be expressed in FFPE tissues from MPM cohort 2.

Copyright © 2022 Elisa Mazzoni et al.

In plain English

This cross-sectional study from Italy looked for signs of simian virus 40 (SV40), a polyomavirus, in people with malignant pleural mesothelioma. The authors tested stored blood serum from 152 mesothelioma patients and 263 healthy subjects. They looked for IgG antibodies against the virus's large T antigen, using a lab test (indirect ELISA) built on two short synthetic pieces of that protein, called A and D. A serum counted as positive only if it reacted to both. Positive sera were found in 34% (51/152) of the patients and 20% (52/263) of the healthy subjects (odds ratio 2.049, 95% CI 1.32 to 3.22). Separately, archived tumor tissue from 20 other mesothelioma patients was stained for the viral protein, and 8 of the 20 (40%) tested positive. The article did not report the participants' asbestos exposure. The authors noted that the serum donors and the tissue donors were different people. The authors concluded that the findings indicate an association between SV40 and mesothelioma but are not proof that SV40 causes the tumor.

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: Cross-sectional (observational) study comparing serum antibodies in mesothelioma patients and healthy subjects, plus immunohistochemical staining of archived tumor tissue from a separate group of mesothelioma patients
• Who was studied: Sera from 152 malignant pleural mesothelioma patients (age range 37–89, mean 68, 68% male) and 263 healthy subjects (age range 49–100, mean 68, 62% male). The healthy subjects attended Sant'Anna Hospital, Ferrara, Italy, for routine blood tests. Sera were collected in 2010 and 2019. In addition, 20 archived formalin-fixed, paraffin-embedded mesothelioma specimens came from patients unrelated to the serum donors.
• Exposure: Serum IgG antibodies against SV40 large T antigen, measured with two synthetic peptides (Tag A and Tag D), and SV40 large T antigen protein in tumor tissue. Asbestos exposure of the participants was not measured or reported.
• Main results:
  • Sera reacting to peptide A: 41% (62/152) of mesothelioma patients vs 25% (67/263) of healthy subjects
  • Sera reacting to peptide D: 37% (57/152) of mesothelioma patients vs 24% (64/263) of healthy subjects
  • Sera reacting to both peptides (the study's definition of positive): 34% (51/152) of mesothelioma patients vs 20% (52/263) of healthy subjects
  • The difference between patients and healthy subjects was reported as statistically significant: odds ratio 2.049, 95% CI 1.32–3.22 (given as 1.32–3.224 elsewhere in the article), p = 0.0026
  • Average antibody signal (optical density, peptides A + D) was higher in mesothelioma patients (0.30, 95% CI 0.26–0.34) than in healthy subjects (0.18, 95% CI 0.17–0.19), p less than 0.0001
  • In archived tumor tissue from 20 separate mesothelioma patients, 8 of 20 (40%) stained positive for SV40 large T antigen. 10 were negative and 1 was not assessable.
• The authors' conclusion: The authors concluded that the antibody and tissue findings indicate an association between SV40 and malignant pleural mesothelioma, but do not prove that SV40 causes the tumor. They speculated that asbestos-exposed people infected with SV40 may be more prone to developing mesothelioma.
• Limitations the authors state:
  • The serum group and the tissue group were different people. Because sera were collected anonymously, the authors could not stain tumor tissue from the same patients whose blood was tested.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, SV40, Asbestos Exposure, Odds Ratio, Immunohistochemistry.

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