1. Center for Reproduction and Health Development, Shenzhen Institutes of Advanced Technology, Chinese Academy of Science, Shenzhen, 518055, China.
2. Carson Cancer Center, Guangdong Key Laboratory for Genome Stability & Disease Prevention, Shenzhen University School of Medicine, Shenzhen, 518055, China.
3. College of Biological and Food Engineering, Huaihua University, "Double First-Class" Applied Characteristic Discipline of Bioengineering in Hunan High Educational Institution, Huaihua, 418000, China.
4. Department of Obstetrics and Gynaecology, the Sixth Affiliated Hospital of Shenzhen University School of Medicine, Shenzhen, 518052, China.
5. Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
6. Department of Oncology, Wuzhou People's Hospital, Wuzhou, 54300, China.
7. Department of Thoracic Surgery, the First Affiliated Hospital of Shenzhen University School of Medicine, Shenzhen, 518055, China.
8. School of Life Science, Heilongjiang University, Harbin, 150080, China.
9. College of Veterinary Medicine, Hunan Agricultural University, Changsha, 410128, China.
*These authors contributed equally to this work.
Rationale: Placental-like chondroitin sulfate A (pl-CSA) is known to be exclusively synthesized in multiple cancer tissues and associated with disease severity. Here, we aimed to assess whether pl-CSA is released into bio-fluids and can serve as a cancer biomarker.
Methods: A novel ELISA was developed to analyse pl-CSA content in bio-fluids using pl-CSA binding protein and an anti-pl-CSA antibody. Immunohistochemical staining of tissue chips was used as the gold standard control.
Results: The developed ELISA method was specific and sensitive (1.22 μg/ml). The pl-CSA content was significantly higher in lysates and supernatants of cancer cell lines than in those of normal cell lines, in plasma from mouse cancer models than in that from control mice, and in plasma from patients with oesophageal, cervical, ovarian, or lung cancer than in that from healthy controls. Similar to the tissue chip analysis, which showed a significant difference in pl-CSA positivity between cancer tissues and normal adjacent tissues, the plasma pl-CSA analysis had 100% sensitivity and specificity for differentiating oesophageal and lung cancer patients from healthy controls. Importantly, in oesophageal and lung cancer patients, the pl-CSA content was significantly higher in late-stage disease than in early-stage disease, and it dramatically decreased after surgical resection of the tumour.
Conclusion: These data indicate a direct link between plasma pl-CSA content and tumour presence, indicating that plasma pl-CSA may be a non-invasive biomarker with clinical applicability for the screening and surveillance of patients with multiple types of solid tumours.
Keywords: circulating pl-CSA, biomarker, cancer screening