Serum Extracellular Vesicles Double-positive for CD9 and CD147 or for CD9 and CD63 Decrease After Surgical Resection in Patients With Colorectal Cancer: Potential Biomarkers of Residual Tumor.
Extracellular vesicles (EVs), including exosomes, are abundant in body fluids, and EV surface proteins can be profiled as potential minimally invasive biomarkers. CD147 (EMMPRIN/Basigin) is a tumor-associated surface glycoprotein implicated in cancer progression. CD9 and CD63 are tetraspanin membrane proteins widely used as EV markers. The present study aimed to evaluate the clinical significance of serum EV subsets double-positive for CD9 and CD63, or for CD9 and CD147 in patients with colorectal cancer (CRC) before and after tumor resection.
Sixteen patients with CRC were recruited, and paired pre- and postoperative serum samples were analyzed for CD9+ CD63+ EVs and CD9+ CD147+ EVs. Serum EVs were quantified using the ExoCounter system with antibody-conjugated beads. CD147 expression in resected tumor tissue was analyzed by immunohistochemistry.
CD9+ CD63+ EVs were significantly reduced in postoperative samples compared with preoperative samples (p=0.0151). CD9+ CD147+ EVs also showed a significant postoperative decrease (p=0.0186). CD147 immunostaining was positive in 13 out of 16 resected tumors (81.3%). In patients with CD147 negative tumors (n=3), serum CD9+ CD147+ EV levels were low at both pre- and postoperative time points and remained unchanged.
Serum CD9+ CD63+ and CD9+ CD147+ EV subsets decreased after CRC surgery, supporting their potential utility as minimally invasive liquid biopsy biomarkers of postoperative tumor burden. Future prospective clinical trials will determine whether these EV subsets are indeed biomarkers of postoperative residual tumor.
Sixteen patients with CRC were recruited, and paired pre- and postoperative serum samples were analyzed for CD9+ CD63+ EVs and CD9+ CD147+ EVs. Serum EVs were quantified using the ExoCounter system with antibody-conjugated beads. CD147 expression in resected tumor tissue was analyzed by immunohistochemistry.
CD9+ CD63+ EVs were significantly reduced in postoperative samples compared with preoperative samples (p=0.0151). CD9+ CD147+ EVs also showed a significant postoperative decrease (p=0.0186). CD147 immunostaining was positive in 13 out of 16 resected tumors (81.3%). In patients with CD147 negative tumors (n=3), serum CD9+ CD147+ EV levels were low at both pre- and postoperative time points and remained unchanged.
Serum CD9+ CD63+ and CD9+ CD147+ EV subsets decreased after CRC surgery, supporting their potential utility as minimally invasive liquid biopsy biomarkers of postoperative tumor burden. Future prospective clinical trials will determine whether these EV subsets are indeed biomarkers of postoperative residual tumor.
Authors
Adachi Adachi, Matsuda Matsuda, Inubushi Inubushi, Yasuda Yasuda, Ito Ito, Shirakami Shirakami, Tachibana Tachibana, Imai Imai, Kagiyama Kagiyama, Tsuneki Tsuneki, Ando Ando, Saito Saito, Sugita Sugita, Ikeda Ikeda, Koterazawa Koterazawa, Aoki Aoki, Harada Harada, Otowa Otowa, Urakawa Urakawa, Goto Goto, Hasegawa Hasegawa, Kanaji Kanaji, Yamashita Yamashita, Hoffman Hoffman, Kakeji Kakeji
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