Platelet-derived growth factor receptor- gene expression relates to recurrence in colorectal cancer
Platelet-derived growth factor receptor- gene expression relates to recurrence in colorectal cancer
复制标题
DOI：
10.3892/or.2018.6290
复制
发表时间：
2018-05-01
期刊：
影响因子：
4.2
通讯作者：
Mori, Masaki
中科院分区：
文献类型：
--
作者：
Fujino, Shiki;Miyoshi, Norikatsu;Mori, Masaki
血小板衍生生长因子受体-(PDGFR-)在上皮性肿瘤中主要由基质细胞表达。PDGFR-α的高表达与多种肿瘤的预后不良有关，但其在结直肠癌(CRC)中的意义尚不清楚。本研究旨在阐明PDGFR-对结直肠癌患者预后的影响。这项研究包括194名接受结直肠癌手术的患者。采用实时定量逆转录聚合酶链式反应和免疫组织化学方法检测PDGFR的表达水平，并与各种临床参数进行相关性分析。通过在结直肠癌细胞系和特异性PDGFR抑制剂crenolanib中的基因敲除实验评价其生物学意义。PDGFR-mRNA和蛋白表达水平呈正相关。根据单变量和多变量分析，PDGFR低表达与根治性手术切除后的无瘤生存率显著高于PDGFR高表达。在两个细胞系中对PDGFR基因敲除的评估表明，小干扰RNA(SiRNA)抑制导致细胞生长和侵袭显著减少。PDGFR抑制剂在体外以剂量依赖的方式抑制结直肠癌细胞的增殖。结论：PDGFR表达是结直肠癌患者复发的危险因素，PDGFR抑制剂可能是治疗结直肠癌的有效药物。
Platelet-derived growth factor receptor- (PDGFR-) in epithelial tumors is mainly expressed by stromal cells. High expression of PDGFR- has been related to poor prognosis in several cancers, however its significance in colorectal cancer (CRC) remains unknown. The present study aimed to clarify the prognostic impact of PDGFR- in CRC patients. The study included 194 patients who underwent surgery for CRC. PDGFR- expression was examined by real-time reverse transcription-polymerase chain reaction and immunohistochemistry and the expression levels were correlated with various clinical parameters. The biological significance was evaluated by knockdown experiments in CRC cell lines and the specific PDGFR inhibitor, crenolanib. PDGFR- mRNA and protein expression levels were positively correlated with each other. Low PDGFR- expression was associated with significantly better disease-free survival after curative surgical resection, than high PDGFR- expression, according to univariate and multivariate analyses. The assessment of PDGFR- knockdown in two cell lines revealed that small interfering RNA (siRNA) inhibition resulted in statistically significant reductions in cell growth and invasion. PDGFR inhibitor suppressed CRC cell proliferation in vitro in a dose-dependent manner. In conclusion, PDGFR- expression was a risk factor for recurrence in patients with CRC and PDGFR inhibitor may be a useful therapeutic agent for CRC.