Journal Article

Circulating Thrombospondin‐4‐Positive Fibroblasts Might be a Useful Marker for Diagnosis of Gastric Cancer

Fukui, Yasuhiro, Kasashima, Hiroaki, Sugimoto, Atsushi, Canfeng, Fan, Aoyama, Rika, Sakuma, Takashi, Kawabata, Kyoka, Sano, Tomoya, Kuroda, Kenji, Yamamoto, Yurie, Nishikubo, Hinano, Yashiro, Masakazu, Imanishi, Daiki, Tsujio, Gen, Sera, Tomohiro, Maruo, Koji, Maeda, Kiyoshi

2026

Overview

Background Cancer‐associated fibroblasts (CAFs) have been reported to be tumor‐specific cells. We have recently reported that thrombospondin‐4 (THBS4) expression is exclusive to CAFs. This study aimed to clarify whether the identification of circulating CAFs (cir‐CAFs) by THBS4 is detectable in the blood of gastric cancer (GC) patients, and whether cir‐CAFs are useful for the screening test of GC. Materials and Methods CAFs and normal fibroblasts (NFs) were respectively established from 17 GC specimens. A total of 24 healthy volunteers and 77 GC patients were enrolled. Flow cytometric analysis was performed using anti‐THBS4 antibody. The sensitivity and specificity of THBS4‐positive cir‐CAFs for detection of GC were calculated. Results THBS4+ cells showed ovoid‐like cells and expressed THBS4. THBS4+ expression was significantly (p = 0.014) higher on CAFs than NFs. GC patients had a significantly (p = 0.0323) higher average number of THBS4‐positive cir‐CAFs than healthy volunteers: 212 cells versus 6.4 cells. The ROC curve indicated that 27 THBS4‐positive cells per 10,000 blood cells was an adequate cutoff for GC diagnosis. The sensitivity and specificity of cir‐CAFs were 76.6% and 100%, respectively. In contrast, the sensitivities of CEA and CA19‐9 were only 22.1% and 9.1%, respectively. The sensitivity of cir‐CAFs was high even for Stage I GC, at 73.5%, while the sensitivity of CEA and CA19‐9 was low at 14.7% and 0%, respectively. Conclusion THBS4‐positive cir‐CAFs are detectable in the blood of GC patients. The cir‐CAFs might be a useful tumor marker in a GC screening test, especially for early‐stage GC.

• Publisher: John Wiley & Sons, Inc,Wiley
• Subject: Adult / Aged / Biomarkers / Biomarkers, Tumor - blood / Biomarkers, Tumor - metabolism / Blood cells / Breast cancer / Cancer-Associated Fibroblasts - metabolism / Cancer-Associated Fibroblasts - pathology / cancer‐associated fibroblast / Case-Control Studies / Diagnosis / early gastric cancer / Endoscopy / Female / Fibroblasts / Fibroblasts - metabolism / Flow cytometry / Gastric cancer / Gastrointestinal surgery / Humans / Immunohistochemistry / Male / Medical prognosis / Middle Aged / Neoplasm Staging / Patients / ROC Curve / Stomach Neoplasms - blood / Stomach Neoplasms - diagnosis / Stomach Neoplasms - pathology / Thrombospondin / Thrombospondins - blood / Thrombospondins - metabolism / Thrombospondin‐4 / tumor marker / Tumor markers / Tumors