UNASSIGNED: Variations of GPIHBP1 messenger RNA (mRNA) levels were first analysed using The Cancer Genome Atlas (TCGA) database. Protein levels of GPIHBP1 in cancer nest cells, stromal cells or surrounding normal tissues from 68 patients with CRC were checked by immunohistochemistry. Infiltration of immune cells such as macrophages, myeloid-derived suppressor cells (MDSCs), CD8+ and CD56+ cells was parallelly stained in the same tissues. Ectopic GPIHBP1 expressed colonic tumour cells were transplanted into the back of mice. Tumour growth and immune cell infiltrations were also observed.
UNASSIGNED: Compared with those in healthy tissues, GPIHBP1 mRNA and protein levels decreased in the patients with CRC at Dukes A-B stage but gradually increased in the patients at Dukes C-D stage. GPIHBP1 in foci or stroma was positively correlated with recruited macrophages or MDSCs and negatively correlated with recruited CD8+, CD56+ or granzyme+ cells. The mice injected with GPIHBP1 overexpression cells bore large tumours. Histological analysis confirmed the infiltration of many macrophages and MDSCs but less CD8+ T or CD56+ cells.
UNASSIGNED: The increased expression of GPIHBP1 is involved in the progression of CRC. High GPIHBP1 level of advanced CRC indicates efficient immune evasion in tumour microenvironment.
首先使用癌症基因组图谱(TCGA)数据库分析GPIHBP1信使RNA(mRNA)水平的变化。癌巢细胞中GPIHBP1的蛋白质水平,通过免疫组织化学检查68例CRC患者的基质细胞或周围正常组织。免疫细胞如巨噬细胞的浸润,骨髓来源的抑制细胞(MDSCs),CD8+和CD56+细胞在相同组织中平行染色。将异位表达GPIHBP1的结肠肿瘤细胞移植到小鼠背部。还观察到肿瘤生长和免疫细胞浸润。
■与健康组织相比,DukesA-B期CRC患者的GPIHBP1mRNA和蛋白水平下降,但DukesC-D期患者的GPIHBP1mRNA和蛋白水平逐渐升高。病灶或间质中的GPIHBP1与募集的巨噬细胞或MDSCs呈正相关,与募集的CD8+呈负相关,CD56+或粒酶+细胞。注射GPIHBP1过表达细胞的小鼠具有大的肿瘤。组织学分析证实了许多巨噬细胞和MDSC的浸润,但CD8+T或CD56+细胞较少。
■GPIHBP1的表达增加与CRC的进展有关。晚期CRC的高GPIHBP1水平表明肿瘤微环境中有效的免疫逃避。