Liang Chaonan, Liu Nan, Zhang Qin, Deng Mingming, Ma Jiangwei, Lu Jingwen, Yin Yan, Wang Jian, Miao Yuan, She Bin, Li Qingchang, Hou Gang
Department of Cardio-Pulmonary Function, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, Henan, China.
Department of Pulmonary and Critical Care Medicine, The First Hospital of China Medical University, Shenyang, China.
Front Oncol. 2022 Sep 13;12:967079. doi: 10.3389/fonc.2022.967079. eCollection 2022.
Cytology remains the gold standard for the detection of malignant cells in pleural effusion. However, its sensitivity is limited. The aim of this study was to establish a novel panel of cancer-specific methylated genes for the differential diagnosis of malignant pleural effusion (MPE).
A cohort of 100 cancer patients (68 lung cancer, 32 other malignant tumors) and 48 patients with benign disease presenting with pleural effusion was prospectively enrolled. Pleural effusion was evaluated by means of cytopathological investigation and DNA methylation of SHOX2, RASSF1A, SEPTIN9 and HOXA9 in the cellular fraction. DNA methylation in bisulfite-converted DNA was determined using quantitative methylation-specific real-time PCR (MS-PCR). Cytopathological and DNA methylation results were evaluated with regard to the final clinical diagnosis.
The LungMe SHOX2 and RASSF1A Assay (Tellgen Corporation, China) has been reported to be highly sensitive and specific for lung cancer using bronchial aspirates. As expected, LungMe detected metastases of lung cancer (sensitivity: 76.5%) as well as metastases of other malignant tumors (sensitivity: 68.8%). OncoMe, a novel combination of SHOX2, RASSF1A, SEPTIN9 and HOXA9 methylation, led to an additional 11% increase in the detection rate of MPE, resulting in a sensitivity of 85% and a specificity of 96%. Overall, OncoMe showed a higher positive detection rate in SCLC (100%), LUAC (87%), OC (100%), BC (92.9%), GC (80.0%), and MESO (80%) than in LUSC (50%). Cytopathological analyses only detected 23 positive samples, which were all positively measured by both LungMe and OncoMe.
OncoMe has potential for use as a biomarker for the detection of MPE, even not limited to lung cancer.
细胞学检查仍是检测胸腔积液中恶性细胞的金标准。然而，其敏感性有限。本研究的目的是建立一组新的癌症特异性甲基化基因，用于鉴别诊断恶性胸腔积液（MPE）。
前瞻性纳入了100例癌症患者（68例肺癌，32例其他恶性肿瘤）和48例有胸腔积液的良性疾病患者。通过细胞病理学检查以及细胞成分中SHOX2、RASSF1A、SEPTIN9和HOXA9的DNA甲基化对胸腔积液进行评估。使用定量甲基化特异性实时PCR（MS-PCR）测定亚硫酸氢盐转化DNA中的DNA甲基化。根据最终临床诊断评估细胞病理学和DNA甲基化结果。
据报道，LungMe SHOX2和RASSF1A检测法（中国泰吉华公司）使用支气管吸出物对肺癌具有高度敏感性和特异性。不出所料，LungMe检测到肺癌转移（敏感性：76.5%）以及其他恶性肿瘤转移（敏感性：68.8%）。OncoMe是SHOX2、RASSF1A、SEPTIN9和HOXA9甲基化的新组合，使MPE的检测率额外提高了11%，敏感性达到85%，特异性达到96%。总体而言，OncoMe在小细胞肺癌（SCLC，100%）、肺腺癌（LUAC，87%）、卵巢癌（OC，100%）、乳腺癌（BC，92.9%）、胃癌（GC，80.0%）和间皮瘤（MESO，80%）中的阳性检测率高于肺鳞癌（LUSC，50%）。细胞病理学分析仅检测到23个阳性样本，LungMe和OncoMe均对其检测为阳性。
OncoMe有潜力用作检测MPE的生物标志物，甚至不限于肺癌。
