Establishment and validation of a plasma oncofetal chondroitin sulfated proteoglycan for pan-cancer detection

Pei-Fen Zhang, Zi-Yi Wu, Wen-Bin Zhang, Yong-Qiao He, Kexin Chen, Tong-Min Wang, Haixin Li, Hong Zheng, Dan-Hua Li, Da-Wei Yang, Ting Zhou, Chang-Mi Deng, Ying Liao, Wen-Qiong Xue, Lian-Jing Cao, Xi-Zhao Li, Jiang-Bo Zhang, Si-Qi Dong, Fang Wang, Mei-Qi Zheng, Wen-Li Zhang, Jianbing Mu () and Wei-Hua Jia ()
Additional contact information
Pei-Fen Zhang: Sun Yat-sen University Cancer Center
Zi-Yi Wu: Sun Yat-sen University Cancer Center
Wen-Bin Zhang: Sun Yat-sen University Cancer Center
Yong-Qiao He: Sun Yat-sen University Cancer Center
Kexin Chen: Tianjin Medical University Cancer Institute and Hospital
Tong-Min Wang: Sun Yat-sen University Cancer Center
Haixin Li: Tianjin Medical University Cancer Institute and Hospital
Hong Zheng: Tianjin Medical University Cancer Institute and Hospital
Dan-Hua Li: Sun Yat-sen University Cancer Center
Da-Wei Yang: Sun Yat-sen University Cancer Center
Ting Zhou: Sun Yat-sen University Cancer Center
Chang-Mi Deng: Sun Yat-sen University Cancer Center
Ying Liao: Sun Yat-sen University Cancer Center
Wen-Qiong Xue: Sun Yat-sen University Cancer Center
Lian-Jing Cao: Sun Yat-sen University Cancer Center
Xi-Zhao Li: Sun Yat-sen University Cancer Center
Jiang-Bo Zhang: Sun Yat-sen University Cancer Center
Si-Qi Dong: Sun Yat-sen University Cancer Center
Fang Wang: Sun Yat-sen University Cancer Center
Mei-Qi Zheng: Sun Yat-sen University Cancer Center
Wen-Li Zhang: Sun Yat-sen University Cancer Center
Jianbing Mu: National Institutes of Health
Wei-Hua Jia: Sun Yat-sen University Cancer Center

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-36374-7

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