Background/Objectives: Gastric and lung adenocarcinomas are among the most common adenocarcinomas worldwide. Our research aimed to validate methylation biomarkers that differentiate gastric and lung adenocarcinomas from hepatocellular carcinoma, cholangiocarcinoma, colorectal carcinoma, pancreatic adenocarcinoma and paired healthy tissues.Methods: The study analyzed 178 formalin-fixed, paraffin-embedded tissue samples, including 14 gastric adenocarcinomas, 15 lung adenocarcinomas, 15 hepatocellular carcinomas, 15 cholangiocarcinomas, 15 colorectal carcinomas, 15 pancreatic adenocarcinomas and their paired healthy tissues. Methylation status was determined experimentally by methylation-sensitive high resolution melting. The diagnostic panels were validated on bioinformatics datasets from The Cancer Genome Atlas and Gene Expression Omnibus, comprising 1981 and 773 samples, respectively. Sensitivity, specificity, diagnostic accuracy and predictive values for each cancer type were calculated for the experimental, Gene Expression Omnibus and The Cancer Genome Atlas datasets.Results: The gastric cancer-specific panel showed a sensitivity of 78.6–83.9%, a specificity of 86.6–94.6% and a diagnostic accuracy of 89.9–96.1% to differentiate between all tumors, and a sensitivity of 78.6–83.9%, a specificity of 89.2–96.4% and a diagnostic accuracy of 88–96.1% to differentiate between all tumors and healthy tissues. The lung adenocarcinoma-specific panel showed a sensitivity of 61.1–93.3%, a specificity of 70.3–90.8% and a diagnostic accuracy of 74.2–90.6% to differentiate between all tumors, and a sensitivity of 61.1–93.3%, a specificity of 77.9–93.4% and a diagnostic accuracy of 79.2% to 93.1% to differentiate between all tumors and healthy tissues.Conclusions: This study demonstrates the potential of using diagnostic methylation panels to differentiate gastric and lung adenocarcinomas from other common adenocarcinomas and paired healthy tissues.
背景/目的:胃腺癌与肺腺癌是全球范围内最常见的腺癌类型。本研究旨在验证能够区分胃腺癌、肺腺癌与肝细胞癌、胆管癌、结直肠癌、胰腺腺癌及其配对健康组织的甲基化生物标志物。 方法:研究分析了178例福尔马林固定石蜡包埋组织样本,包括14例胃腺癌、15例肺腺癌、15例肝细胞癌、15例胆管癌、15例结直肠癌、15例胰腺腺癌及其配对健康组织。通过甲基化敏感高分辨率熔解曲线实验测定甲基化状态。诊断组合在癌症基因组图谱和基因表达综合数据库的生物信息学数据集(分别包含1981例和773例样本)中得到验证。针对实验数据集、基因表达综合数据库及癌症基因组图谱数据集,分别计算了各癌症类型的敏感性、特异性、诊断准确率及预测值。 结果:胃癌特异性诊断组合在区分所有肿瘤时表现出78.6–83.9%的敏感性、86.6–94.6%的特异性及89.9–96.1%的诊断准确率;在区分所有肿瘤与健康组织时表现出78.6–83.9%的敏感性、89.2–96.4%的特异性及88–96.1%的诊断准确率。肺腺癌特异性诊断组合在区分所有肿瘤时表现出61.1–93.3%的敏感性、70.3–90.8%的特异性及74.2–90.6%的诊断准确率;在区分所有肿瘤与健康组织时表现出61.1–93.3%的敏感性、77.9–93.4%的特异性及79.2%至93.1%的诊断准确率。 结论:本研究证实了利用诊断性甲基化组合区分胃腺癌、肺腺癌与其他常见腺癌及配对健康组织的潜在应用价值。