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Original research
Combined detection of SHOX2 and PTGER4 methylation with serum marker CYFRA21-1 for improved diagnosis of malignant pleural mesothelioma
  1. Nana Zhang1,
  2. Yongmeng Li1,
  3. Zuyu Sun1,
  4. Yujie Dong1,
  5. Lijuan Zhou1,
  6. Chen Zhang1,
  7. Zichen Liu1,
  8. Qiuyi Zhang1,
  9. Kun Li1,
  10. Fudong Xu1,
  11. Li Zhang1,
  12. Bin She2,
  13. Xiaosha Ren2,
  14. Nanying Che1
  1. 1Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis & Thoracic Tumor Research Institute, Tongzhou District, Beijing, China
  2. 2Shanghai Methyldia Technology Co, Shanghai, China
  1. Correspondence to Dr Nanying Che, Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beiguandajie 9#, Tongzhou Dist, Beijing 101149, China; cheny0448{at}163.com

Abstract

Aims To investigate the performance of a combined biomarker approach using the methylation status of the short stature homeobox 2 (SHOX2) and prostaglandin E2 receptor EP4 (PTGER4) genes, along with the serum levels of CYFRA21-1, for differential diganosis of malignant pleural mesothelioma (MPM) from benign reactive mesothelial hyperplasia (RMH).

Methods We analysed 48 MPM tissue or pleural effusion cell block specimens and 42 cases with RMH. Real-time quantitative methylation-specific PCR was used to examine the methylation status of SHOX2, PTGER4, ras association domain family 1 isoform A, septin 9 gene and homeobox gene A9 genes. Additionally, we employed electrochemiluminescence immunoassay to measure nine serum tumour markers commonly used in pan-cancer screening tests.

Results The receiver operating curve indicated that SHOX2, PTGER4 gene methylation and serum biomarker CYFRA21-1 exhibited good diagnostic performance in identifying MPM, with area under curves (AUCs) of 0.761, 0.904 and 0.847, respectively. The combination of SHOX2, PTGER4 methylation and CYFRA21-1 yielded an AUC value of 0.972. The diagnostic sensitivity and specificity of this panel in differentiating MPM from RMH were 91.3% (42/46) and 97.6% (41/42), respectively. Both tissue and cell block specimens can be used in the diagnostic process. Furthermore, elevated CYFRA21-1 levels were associated with poor prognosis (p<0.05). Hypermethylation level of PTGER4 may indicate an unfavourable prognosis of MPM, but the difference was not statistically significant.

Conclusions The combined detection of SHOX2 and PTGER4 methylation alongside serum CYFRA21-1 level significantly enhances the diagnosis of MPM. Additionally, CYFRA21-1 can serve as a prognostic indicator for MPM.

  • Biomarkers, Tumor
  • Diagnostic Techniques and Procedures
  • Pathology, Molecular

Data availability statement

Data are available upon reasonable request.

https://doi.org/10.1136/jcp-2024-209592

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    Data availability statement

    Data are available upon reasonable request.

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    Footnotes

    • Handling editor Vikram Deshpande.

    • NZ, YL and ZS contributed equally.

    • Contributors NC and NZ conceived and directed the study. NZ, YL, ZS, CZ, FX, LZhou, ZL, QZ, LZhang and KL performed the experiments. YD performed the histological examination of diseases. NZ, YL, ZS, XR and BS contributed to data analyses. NZ, YL, ZS and NC drafted the manuscript. NC is the guarantor. All authors read and approved the final manuscript.

    • Funding This work was supported by grants from the National Natural Science Foundation of China (82072381), Beijing Municipal Administration of Hospitals Incubating Program (PX2022065), Beijing Municipal Science and Technology Project (Z181100001918027, Z191100006619079) and Tongzhou High-level Technique Talents Program (YHLD2018006).

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.