ITIH3 Is a Potential Biomarker for Early Detection of Gastric Cancer

Gastric cancer has one of the highest morbidities and mortalities worldwide. Early detection is key measure to improve the outcome of gastric cancer patients. In our efforts to identify potential markers for gastric cancer detection, we coupled xenotransplantation mouse model with a plasma proteomic approach. MKN45 gastric cancer cells were subcutaneously injected into nude mice and plasma samples from mice bearing different sizes of tumors were collected and subjected to iTRAQ and mass spectrometry analysis. ITIH3 protein was found to be more highly expressed in plasma of tumor bearing mice compared to control. Subsequent screening of ITIH3 expression in 167 clinical plasma samples, including 83 cancer-free subjects and 84 gastric cancer patients, revealed higher ITIH3 level in the plasma of gastric cancer patients. A receiver operating characteristics (ROC) curve estimated a maximal sensitivity of 96% at 66% specificity for ITIH3 in gastric cancer detection. In addition, plasma from early stage gastric cancer patient has significantly (p < 0.001) higher level of ITIH3 compared to that from noncancer subject. Our data suggest that ITIH3 may be a useful biomarker for early detection of gastric cancer.胃癌是全球发病率与死亡率最高的肿瘤类型之一，早期筛查是改善胃癌患者预后的关键举措。为筛选胃癌检测的潜在生物标志物，本研究将异种移植小鼠模型（xenotransplantation mouse model）与血浆蛋白质组学方法相结合：将MKN45胃癌细胞皮下接种至裸鼠体内，收集携带不同体积肿瘤的小鼠血浆样本，采用iTRAQ与质谱分析法进行检测。研究发现，与对照组相比，荷瘤小鼠血浆中ITIH3蛋白的表达水平显著升高。随后对167份临床血浆样本（含83名健康对照者与84名胃癌患者）的ITIH3表达水平进行检测，结果显示胃癌患者血浆中的ITIH3水平显著升高。受试者工作特征（ROC）曲线分析表明，ITIH3用于胃癌检测时，在特异性为66%的前提下，最大灵敏度可达96%。此外，早期胃癌患者的血浆ITIH3水平较健康对照者显著升高（p < 0.001）。本研究结果提示，ITIH3或可成为胃癌早期检测的有效生物标志物。