Non-invasive early detection of cancer four years before conventional diagnosis using a blood test.
Chen Xingdong,Gole Jeffrey,Gore Athurva,He Qiye,Lu Ming,Min Jun,Yuan Ziyu,Yang Xiaorong,Jiang Yanfeng,Zhang Tiejun,Suo Chen,Li Xiaojie,Cheng Lei,Zhang Zhenhua,Niu Hongyu,Li Zhe,Xie Zhen,Shi Han,Zhang Xiang,Fan Min,Wang Xiaofeng,Yang Yajun,Dang Justin,McConnell Catie,Zhang Juan,Wang Jiucun,Yu Shunzhang,Ye Weimin,Gao Yuan,Zhang Kun,Liu Rui,Jin Li
Early detection has the potential to reduce cancer mortality, but an effective screening test must demonstrate asymptomatic cancer detection years before conventional diagnosis in a longitudinal study. In the Taizhou Longitudinal Study (TZL), 123,115 healthy subjects provided plasma samples for long-term storage and were then monitored for cancer occurrence. Here we report the preliminary results of PanSeer, a noninvasive blood test based on circulating tumor DNA methylation, on TZL plasma samples from 605 asymptomatic individuals, 191 of whom were later diagnosed with stomach, esophageal, colorectal, lung or liver cancer within four years of blood draw. We also assay plasma samples from an additional 223 cancer patients, plus 200 primary tumor and normal tissues. We show that PanSeer detects five common types of cancer in 88% (95% CI: 80-93%) of post-diagnosis patients with a specificity of 96% (95% CI: 93-98%), We also demonstrate that PanSeer detects cancer in 95% (95% CI: 89-98%) of asymptomatic individuals who were later diagnosed, though future longitudinal studies are required to confirm this result. These results demonstrate that cancer can be non-invasively detected up to four years before current standard of care.
Purification of HCC-specific extracellular vesicles on nanosubstrates for early HCC detection by digital scoring.
Sun Na,Lee Yi-Te,Zhang Ryan Y,Kao Rueihung,Teng Pai-Chi,Yang Yingying,Yang Peng,Wang Jasmine J,Smalley Matthew,Chen Pin-Jung,Kim Minhyung,Chou Shih-Jie,Bao Lirong,Wang Jing,Zhang Xinyue,Qi Dongping,Palomique Juvelyn,Nissen Nicolas,Han Steven-Huy B,Sadeghi Saeed,Finn Richard S,Saab Sammy,Busuttil Ronald W,Markovic Daniela,Elashoff David,Yu Hsiao-Hua,Li Huiying,Heaney Anthony P,Posadas Edwin,You Sungyong,Yang Ju Dong,Pei Renjun,Agopian Vatche G,Tseng Hsian-Rong,Zhu Yazhen
We report a covalent chemistry-based hepatocellular carcinoma (HCC)-specific extracellular vesicle (EV) purification system for early detection of HCC by performing digital scoring on the purified EVs. Earlier detection of HCC creates more opportunities for curative therapeutic interventions. EVs are present in circulation at relatively early stages of disease, providing potential opportunities for HCC early detection. We develop an HCC EV purification system (i.e., EV Click Chips) by synergistically integrating covalent chemistry-mediated EV capture/release, multimarker antibody cocktails, nanostructured substrates, and microfluidic chaotic mixers. We then explore the translational potential of EV Click Chips using 158 plasma samples of HCC patients and control cohorts. The purified HCC EVs are subjected to reverse-transcription droplet digital PCR for quantification of 10 HCC-specific mRNA markers and computation of digital scoring. The HCC EV-derived molecular signatures exhibit great potential for noninvasive early detection of HCC from at-risk cirrhotic patients with an area under receiver operator characteristic curve of 0.93 (95% CI, 0.86 to 1.00; sensitivity = 94.4%, specificity = 88.5%).