Sudo Tomoya, Takahashi Yusuke, Sawada Genta, Uchi Ryutaro, Mimori Koshi, Akagi Yoshito
Department of Surgery, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.
Department of Surgery and Molecular Oncology, Medical Institute of Bioregulation, Kyushu University, Beppu, Oita 847-0838, Japan.
Oncol Lett. 2017 Jul;14(1):801-809. doi: 10.3892/ol.2017.6257. Epub 2017 May 26.
Integrin-associated protein (CD47) is ubiquitously expressed on the surface of cells and functions as an identifier of self. In blood cancer, tumor cells expressing CD47 evade phagocytosis by macrophages, leading to a poor patient prognosis. However, the status of CD47 expression in solid tumors, particularly in gastric cancer, is not well understood. The purpose of the present study was to examine the level of CD47 in the primary tumor, peripheral blood (PB) and bone marrow (BM) of patients with gastric cancer, and to determine its effect. Reverse transcription-quantitative polymerase chain reaction analysis was performed to determine the level of CD47 mRNA expression in primary tumor, PB and BM samples collected from 168 patients with gastric cancer. Cell sorting was performed to investigate CD47 protein expression in PB and BM fractions, and to identify the source of CD47 expression. In primary tumors, the expression of CD47 was not associated with any clinicopathological factors or prognosis. By contrast, in PB, the low CD47 expression group demonstrated a significantly increased tumor size, and frequency of lymphatic invasion and lymph node metastasis, compared with the high CD47 expression group. In addition, the clinical tumor stage of the low CD47 expression group was significantly increased compared with that of the high CD47 expression group. Conversely, in PB, the high CD47 expression group had a significantly higher frequency of lymphatic invasion and lymph node metastasis compared with the low CD47 expression group. The lymphocyte fraction exhibited the highest CD47 expression compared with the other fractions in PB and BM samples. Low expression of CD47 was associated with the advancement of gastric cancer, in contrast to other cancers, and it may be associated with a decrease in lymphocytes during later stages. These results indicate that CD47 expression in the PB and BM may serve as a marker to analyze the immunological function of patients with gastric cancer; however, the significance of CD47 in gastric cancer requires further study.
整合素相关蛋白(CD47)在细胞表面普遍表达,起到自身识别的作用。在血癌中,表达CD47的肿瘤细胞可逃避巨噬细胞的吞噬作用,导致患者预后不良。然而,实体瘤尤其是胃癌中CD47的表达状况尚不清楚。本研究旨在检测胃癌患者原发肿瘤、外周血(PB)和骨髓(BM)中CD47的水平,并确定其作用。采用逆转录定量聚合酶链反应分析,以确定从168例胃癌患者采集的原发肿瘤、PB和BM样本中CD47 mRNA的表达水平。进行细胞分选以研究PB和BM组分中CD47蛋白的表达,并确定CD47表达的来源。在原发肿瘤中,CD47的表达与任何临床病理因素或预后均无关。相比之下,在PB中,与高CD47表达组相比,低CD47表达组的肿瘤大小、淋巴浸润和淋巴结转移频率显著增加。此外,低CD47表达组的临床肿瘤分期与高CD47表达组相比显著增加。相反,在PB中,高CD47表达组的淋巴浸润和淋巴结转移频率显著高于低CD47表达组。与PB和BM样本中的其他组分相比,淋巴细胞组分的CD47表达最高。与其他癌症不同,CD47低表达与胃癌进展相关,可能与晚期淋巴细胞减少有关。这些结果表明,PB和BM中的CD47表达可能作为分析胃癌患者免疫功能的标志物;然而,CD47在胃癌中的意义仍需进一步研究。