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- Title
Establishment and validation of a plasma oncofetal chondroitin sulfated proteoglycan for pan-cancer detection.
- Authors
Zhang, Pei-Fen; Wu, Zi-Yi; Zhang, Wen-Bin; He, Yong-Qiao; Chen, Kexin; Wang, Tong-Min; Li, Haixin; Zheng, Hong; Li, Dan-Hua; Yang, Da-Wei; Zhou, Ting; Deng, Chang-Mi; Liao, Ying; Xue, Wen-Qiong; Cao, Lian-Jing; Li, Xi-Zhao; Zhang, Jiang-Bo; Dong, Si-Qi; Wang, Fang; Zheng, Mei-Qi
- Abstract
Various biomarkers targeting cell-free DNA (cfDNA) and circulating proteins have been tested for pan-cancer detection. Oncofetal chondroitin sulfate (ofCS), which distinctively modifies proteoglycans (PGs) of most cancer cells and binds specifically to the recombinant Plasmodium falciparum VAR2CSA proteins (rVAR2), is explored for its potential as a plasma biomarker in pan-cancer detection. To quantitate the plasma ofCS/ofCSPGs, we optimized an ELISA using different capture/detection pairs (rVAR2/anti-CD44, -SDC1, and -CSPG4) in a case-control study with six cancer types. We show that the plasma levels of ofCS/ofCSPGs are significantly higher in cancer patients (P values, 1.2 × 10−2 to 4.4 × 10−10). Validation studies are performed with two independent cohorts covering 11 malignant tumors. The individuals in the top decile of ofCS-CD44 have more than 27-fold cancer risk (OR = 27.8, 95%CI = 18.8–41.4, P = 2.72 × 10−62) compared with the lowest 20%. Moreover, the elevated plasma ofCS-CD44 could be detected at the early stage of pan-cancer with strong dose-dependent odds risk prediction. Developing multi-cancer early detection (MCED) tests based on cfDNA or protein markers holds great promise for effective cancer screening. Here, the authors show a sensitive, non-invasive pan-cancer detection method that concurrently detects the oncofetal chondroitin sulfate (ofCS) glycans and its protein backbone in plasma.
- Subjects
CIRCULATING tumor DNA; CHONDROITIN sulfates; CHONDROITIN; CHONDROITIN sulfate proteoglycan; PROTEOGLYCANS; CELL-free DNA; BLOOD proteins; GLYCANS
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-36374-7