Engaru Kosei General Hospital, Chome-1-5 Odorikita, Engaru, Mombetsu District, Hokkaido 099-0404, Japan.
Hirotsu Bio Science Inc., New Otani Garden Court 22F, 4-1 Kioi-cho, Chiyoda-ku, Tokyo, 102-0094, Japan.
Cancer Treat Res Commun. 2021;27:100370. doi: 10.1016/j.ctarc.2021.100370. Epub 2021 Apr 9.
Early cancer detection is critical for effective treatment. N-NOSE (Nematode-NOSE) is a simple, inexpensive, and highly sensitive cancer screening method based on the chemotaxis of the nematode Caenorhabditis elegans, which shows evasive action from the urine of healthy individuals while being attracted to the urine of cancer patients. Initially, N-NOSE relied on chemotaxis indexes obtained with 10-fold dilutions of urine samples. However, cancer tissue size and concentrations of cancer odors differ among cancer patients. In this study, we examined the accuracy improvement of N-NOSE method by using two types of dilutions, 10-fold and 100-fold. We have conducted N-NOSE tests with urine samples from 32 cancer patients (esophageal, gastric, colorectal, gallbladder, cholangiocarcinoma, breast, malignant lymphoma, and acute myeloid leukemia) along with 143 healthy subjects. Our data showed a significant difference in the N-NOSE at 10-fold dilution between the two groups (p < 0.0001), with an area under the ROC curve (AUC) of 0.9188 based on receiver operating characteristic (ROC) analysis. N-NOSE index at 100-fold dilutions was also significantly different between the two groups (p < 0.0001), with an AUC of 0.9032 based on ROC analysis. In this clinical study, we further improve N-NOSE with a combined method of two dilutions (10-fold and 100-fold) of urine samples, which results in a markedly improvement in cancer detection sensitivity of 87.5%. N-NOSE sensitivity improvement was significantly high even for early-stage cancer detection, which is in stark contrast with the sensitivity of detection using blood tumor markers (CEA, CA19-9 and CA15-3). These results strongly suggest that the N-NOSE test by this new combined method strikes a good balance between sensitivity and specificity.
早期癌症检测对于有效治疗至关重要。N-NOSE（线虫-鼻）是一种简单、廉价且高度敏感的癌症筛查方法，基于秀丽隐杆线虫的趋化性，它会避开健康个体的尿液，而被癌症患者的尿液吸引。最初，N-NOSE 依赖于用尿液样本进行 10 倍稀释获得的趋化指数。然而，癌症组织的大小和癌症气味的浓度在不同的癌症患者之间有所不同。在这项研究中，我们通过使用两种稀释度（10 倍和 100 倍）来检查 N-NOSE 方法的准确性提高情况。我们对 32 名癌症患者（食管癌、胃癌、结直肠癌、胆囊癌、胆管癌、乳腺癌、恶性淋巴瘤和急性髓系白血病）以及 143 名健康受试者的尿液样本进行了 N-NOSE 测试。我们的数据显示，两组在 10 倍稀释的 N-NOSE 之间存在显著差异（p<0.0001），基于接受者操作特征（ROC）分析，ROC 曲线下面积（AUC）为 0.9188。两组在 100 倍稀释的 N-NOSE 指数之间也存在显著差异（p<0.0001），基于 ROC 分析，AUC 为 0.9032。在这项临床研究中，我们进一步通过两种尿液样本稀释度（10 倍和 100 倍）的组合方法改进了 N-NOSE，从而使癌症检测的敏感性显著提高到 87.5%。即使是早期癌症的检测，N-NOSE 的敏感性提高也非常显著，与血液肿瘤标志物（CEA、CA19-9 和 CA15-3）的检测灵敏度形成鲜明对比。这些结果强烈表明，这种新的组合方法的 N-NOSE 测试在敏感性和特异性之间取得了很好的平衡。
