Yokose Takahiro, Kabe Yasuaki, Matsuda Atsushi, Kitago Minoru, Matsuda Sachiko, Hirai Miwa, Nakagawa Tomomi, Masugi Yohei, Hishiki Takako, Nakamura Yuki, Shinoda Masahiro, Yagi Hiroshi, Abe Yuta, Oshima Go, Hori Shutaro, Nakano Yutaka, Honda Kazufumi, Kashiro Ayumi, Morizane Chigusa, Nara Satoshi, Kikuchi Shojiro, Shibahara Takahiko, Itonaga Makoto, Ono Masayuki, Minegishi Naoko, Koshiba Seizo, Yamamoto Masayuki, Kuno Atsushi, Handa Hiroshi, Sakamoto Michiie, Suematsu Makoto, Kitagawa Yuko
Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan.
Department of Biochemistry, Keio University School of Medicine, Tokyo 160-8582, Japan.
Cancers (Basel). 2020 Aug 31;12(9):2469. doi: 10.3390/cancers12092469.
Pancreatic cancer (PC) is among the most lethal malignancies due to an often delayed and difficult initial diagnosis. Therefore, the development of a novel, early stage, diagnostic PC marker in liquid biopsies is of great significance. In this study, we analyzed the differential glycomic profiling of extracellular vesicles (EVs) derived from serum (two cohorts including 117 PC patients and 98 normal controls) using lectin microarray. The glyco-candidates of PC-specific EVs were quantified using a high-sensitive exosome-counting system, ExoCounter. An absolute quantification system for altered glycan-containing EVs elevated in PC serum was established. EVs recognized by -glycan-binding lectins ABA or ACA were identified as candidate markers by lectin microarray. Quantitative analyses using ExoCounter revealed that the ABA- or ACA-positive EVs were significantly increased in the culture of PC cell lines or in the serum of PC patients including carbohydrate antigen 19-9 negative patients with high area under curve values. The elevated numbers of EVs in PC serum returned to normal levels after pancreatectomy. Histological examination confirmed that the tumors stained with ABA/ACA. These specific EVs with -glycans recognized by ABA/ACA are elevated in PC sera and can act as potential biomarkers in a liquid biopsy for PC patients screening.
胰腺癌（PC）是最致命的恶性肿瘤之一，因为其初始诊断往往延迟且困难。因此，在液体活检中开发一种新型的早期诊断PC标志物具有重要意义。在本研究中，我们使用凝集素微阵列分析了来自血清的细胞外囊泡（EVs）（两个队列，包括117例PC患者和98例正常对照）的差异糖组学谱。使用高灵敏度外泌体计数系统ExoCounter对PC特异性EVs的糖候选物进行定量。建立了一种用于定量PC血清中升高的含聚糖EVs的绝对定量系统。通过凝集素微阵列将被β-聚糖结合凝集素ABA或ACA识别的EVs鉴定为候选标志物。使用ExoCounter进行的定量分析表明，在PC细胞系培养物或PC患者血清中，包括曲线下面积值高的糖类抗原19-9阴性患者，ABA或ACA阳性EVs显著增加。胰腺切除术后，PC血清中升高的EVs数量恢复到正常水平。组织学检查证实肿瘤被ABA/ACA染色。这些被ABA/ACA识别的带有β-聚糖的特异性EVs在PC血清中升高，可作为液体活检中PC患者筛查的潜在生物标志物。
