Zhang Nana, Li Yongmeng, Sun Zuyu, Dong Yujie, Zhou Lijuan, Zhang Chen, Liu Zichen, Zhang Qiuyi, Li Kun, Xu Fudong, Zhang Li, She Bin, Ren Xiaosha, Che Nanying
Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis & Thoracic Tumor Research Institute, Tongzhou District, Beijing, China.
Shanghai Methyldia Technology Co, Shanghai, China.
J Clin Pathol. 2024 Jul 26. doi: 10.1136/jcp-2024-209592.
To investigate the performance of a combined biomarker approach using the methylation status of the short stature homeobox 2 () and prostaglandin E2 receptor EP4 () genes, along with the serum levels of CYFRA21-1, for differential diganosis of malignant pleural mesothelioma (MPM) from benign reactive mesothelial hyperplasia (RMH).
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 , , 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.
The receiver operating curve indicated that , 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 , 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 may indicate an unfavourable prognosis of MPM, but the difference was not statistically significant.
The combined detection of and methylation alongside serum CYFRA21-1 level significantly enhances the diagnosis of MPM. Additionally, CYFRA21-1 can serve as a prognostic indicator for MPM.
研究联合生物标志物方法的性能，该方法利用矮小同源框2（ SHOX2 ）和前列腺素E2受体EP4 （ PTGER4 ）基因的甲基化状态，以及细胞角蛋白19片段（CYFRA21-1）的血清水平，用于鉴别诊断恶性胸膜间皮瘤（MPM）与良性反应性间皮增生（RMH）。
我们分析了48例MPM组织或胸腔积液细胞块标本以及42例RMH病例。采用实时定量甲基化特异性PCR检测SHOX2、PTGER4、RAS关联结构域家族1异构体A（RASSF1A）、 Septin 9基因和同源框基因A9 （HOXA9）基因的甲基化状态。此外，我们采用电化学发光免疫分析法检测泛癌筛查试验中常用的9种血清肿瘤标志物。
受试者工作特征曲线表明，SHOX2、PTGER4基因甲基化和血清生物标志物CYFRA21-1在识别MPM方面具有良好的诊断性能，曲线下面积（AUC）分别为0.761、0.904和0.847。SHOX2、PTGER4甲基化与CYFRA21-1联合检测的AUC值为0.972。该检测组合在区分MPM与RMH中的诊断敏感性和特异性分别为91.3%（42/46）和97.6%（41/42）。组织和细胞块标本均可用于诊断过程。此外，CYFRA21-1水平升高与预后不良相关（p<0.05）。PTGER4的高甲基化水平可能表明MPM预后不良，但差异无统计学意义。
联合检测SHOX2和PTGER4甲基化以及血清CYFRA21-1水平可显著提高MPM的诊断率。此外，CYFRA21-1可作为MPM的预后指标。
