An analysis of succinate dehydrogenase B in pleural mesothelioma

Our plain-English summary of An analysis of succinate dehydrogenase B in pleural mesothelioma, by C.J. Jennings, S.J. Marciniak, G. Pinton, et al (Discover Oncology, 2026).

The study

• Authors: C.J. Jennings, S.J. Marciniak, G. Pinton, D.M. Rassl, L. Moro, K.J. O'Byrne, R.C. Rintoul, S.P. Finn, L. Mutti, W. Thomas, S.G. Gray
• Journal: Discover Oncology
• Published: 2026;17(1)
• Read it: PubMed · Publisher · Free full text

Abstract

Aim: To investigate the expression of succinate dehydrogenase B and its potential as a therapeutic target in pleural mesothelioma (PM).

Methods: The expression of succinate dehydrogenase B was examined in cell lines using PCR. The expression of succinate dehydrogenase B mRNA was subsequently examined in a series of fresh-frozen primary patient samples using reverse transcription polymerase chain reaction. The expression of succinate dehydrogenase B protein was examined by immunohistochemistry on a pleural mesothelioma tissue microarray derived from Formalin-Fixed and Paraffin-Embedded specimens to determine if succinate dehydrogenase B expression correlated with survival benefit. Using a resazurin-based assay we examined whether targeting the mitochondrial complex II (containing succinate dehydrogenase B) with a chemical inhibitor could have effects on cell proliferation.

Results: Total ribonucleic acid was isolated from a panel of mesothelial-derived cell lines (both cancerous and non-cancerous), and expression of succinate dehydrogenase B messenger RNA was assessed by RT-PCR and found to be ubiquitously expressed. Total Ribonucleic acid was isolated from a panel of fresh-frozen surgical specimens, and succinate dehydrogenase B was significantly overexpressed in mesothelioma at the messenger RNA level. Immunohistochemical staining and analysis of a mesothelioma tissue microarray showed that expression did not correlate with any survival benefit, confirmed by in silico analyses of other datasets. However, links between DNA methylation at individual residues of the succinate dehydrogenase B gene and overall survival were identified, along with correlations to immune cell infiltrates. Targeting the mitochondrial complex II with oxaloacetic acid did not show any significant potential for higher efficacy in cell lines derived from malignant tumors compared to those derived from normal mesothelial cells.

Conclusions: Our results demonstrate that succinate dehydrogenase B is overexpressed in PM but may not be a suitable candidate for therapeutic targeting in this disease.

© 2026. The Author(s).

In plain English

This laboratory study looked at succinate dehydrogenase B (SDHB), part of the energy-producing machinery inside cells, in pleural mesothelioma. It did not measure anyone's asbestos exposure. SDHB messenger RNA was found in every cell line tested, including normal mesothelial cell lines. SDHB was significantly higher in 17 mesothelioma tumors than in 5 benign samples (p = 0.0029). When tumors were split by type, the increase was significant only in the biphasic type. In a public dataset of 87 mesotheliomas, overexpression was rare. Among 61 patients whose tissue could be scored, SDHB protein level was not significantly linked to overall survival. In public data, higher methylation (a chemical tag on DNA) at three sites near the SDHB gene was linked to better survival. In lab tests, oxaloacetic acid affected the growth of two mesothelioma cell lines at lower concentrations than one normal cell line. The article's abstract says SDHB may not suit targeting by therapy. Its final conclusion calls it potentially a target needing further study. The authors noted their sample was small and that cell lines differ from normal tissue.

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 study: SDHB RNA measured in cell lines and surgical tissue, SDHB protein stained in a tissue microarray with survival analysis, analyses of public datasets, and a drug test on cell lines
• Who was studied: Surgical samples from Glenfield Hospital, Leicester, UK (5 benign lesions, 17 pleural mesotheliomas: 7 epithelioid, 4 sarcomatoid, 6 biphasic). Also a tissue microarray of 135 mesothelioma cases diagnosed at Papworth Hospital, Cambridge, 2005 to 2010, of which 61 could be scored. Also normal mesothelial and mesothelioma cell lines and the public TCGA-MESO dataset
• Exposure: Asbestos exposure was not studied. The tested treatment was oxaloacetic acid, an inhibitor of mitochondrial complex II, applied to cell lines for 72 hours
• Main results:
  • SDHB mRNA was detected in all cell lines tested, normal and malignant
  • SDHB mRNA was significantly higher in mesothelioma tumor samples (n = 17) than in benign pleura (n = 5), p = 0.0029
  • By histological subtype, significant overexpression was seen only in biphasic tumors
  • In the TCGA-MESO dataset (n = 87 pleural mesotheliomas), SDHB overexpression was rare
  • In the tissue microarray (61 scorable patients), SDHB protein was not significantly associated with overall survival. Median survival was 221.5 days for patients with a staining score of 3 or lower and 493 days for a score of 4 or higher, a difference that was not significant
  • In the TCGA-MESO dataset, SDHB mRNA was significantly higher in patients with a TP53 mutation
  • In the TCGA-MESO dataset, methylation at three CpG sites near the SDHB gene was associated with better overall survival
  • Oxaloacetic acid significantly affected proliferation at lower concentrations in mesothelioma cell lines (REN and NCI-H226) than in the normal mesothelial cell line (LP9). This is as reported in the results; the abstract states the opposite
• The authors' conclusion: In the final section, the authors concluded that SDHB is overexpressed and potentially a target for therapy in pleural mesothelioma, with further studies needed. The abstract instead concludes that SDHB may not be a suitable therapeutic target
• Limitations the authors state:
  • Much of the data comes from the TCGA-MESO dataset, which cannot be validated and lacks normal pleura data
  • SDHB is expressed in all cell lines, including normal ones, but not in normal pleural tissue, so the cell-line drug and methylation results need caution
  • Too few samples to compare histological subtypes
  • Only 61 of 135 tissue microarray cases could be scored
  • Complex II inhibitors are not readily available and may have limited clinical activity

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Immunohistochemistry, Mesothelioma, Overall Survival, Mesothelial Cells.

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