Li Shu-Qin, Yu Yang, Zhang Yan, Sun Yan-Ping, Li Xin-Xing, Su Ning
School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China.
School of Pharmacy, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 197 Ruijin Road (No.2), Shanghai, 200025, China.
J Cancer. 2020 Mar 25;11(12):3580-3587. doi: 10.7150/jca.36355. eCollection 2020.
Formyl peptide receptor 1 (FPR1) belongs to G protein-coupled receptors expressed mainly in phagocytic leukocytes. The gene encoding FPR1 is highly polymorphic and related to inflammation. In this study, we investigated the single nucleotide polymorphisms (SNPs) of Fpr1 in human colorectal cancer (CRC), and analyzed the association of Fpr1 SNPs with clinicopathological parameters and some specific diagnostic markers of CRC. Although the allele and genotype frequencies of Fpr1 SNPs in CRC tissues were not significantly different from that in whole blood cells derived from healthy Chinese subjects. Significant associations were observed between genotypes of c.289C>A and distant metastasis (P=0.001), and between genotypes of c.306T>C and tumor size (P=0.016). Genotypes of c.546C>A was closer to tumor size and lymphatic invasion (P=0.012 and P=0.043, respectively). Meanwhile, genotypes of c.1037C>A was related with tumor location and differentiation (P=0.000 and P=0.005, respectively). Besides, genotypes of c.576T>C>G was related with pathological type (P=0.000). Furthermore, several Fpr1 SNP positions including c.289 (C>A) and c.576 (G>C>T) were related to the expression of P53 (P=0.004 and P=0.008, respectively), and similar results were observed between other Fpr1 SNP positions and CEA, HER2 and Ki-67 (P<0.05). Our data demonstrate that Fpr1 SNPs may play the important role in the progression and metastasis of CRC.
甲酰肽受体1(FPR1)属于主要在吞噬性白细胞中表达的G蛋白偶联受体。编码FPR1的基因具有高度多态性且与炎症相关。在本研究中,我们调查了人类结直肠癌(CRC)中Fpr1的单核苷酸多态性(SNP),并分析了Fpr1 SNP与CRC临床病理参数及一些特定诊断标志物的相关性。尽管CRC组织中Fpr1 SNP的等位基因和基因型频率与来自健康中国受试者的全血细胞中的频率无显著差异。但观察到c.289C>A基因型与远处转移之间存在显著关联(P = 0.001),c.306T>C基因型与肿瘤大小之间存在显著关联(P = 0.016)。c.546C>A基因型与肿瘤大小和淋巴浸润更相关(分别为P = 0.012和P = 0.043)。同时,c.1037C>A基因型与肿瘤位置和分化相关(分别为P = 0.000和P = 0.005)。此外,c.576T>C>G基因型与病理类型相关(P = 0.000)。此外,包括c.289(C>A)和c.576(G>C>T)在内的几个Fpr1 SNP位点与P53的表达相关(分别为P = 0.004和P = 0.008),在其他Fpr1 SNP位点与癌胚抗原(CEA)、人表皮生长因子受体2(HER2)和Ki-67之间也观察到类似结果(P<0.05)。我们的数据表明,Fpr1 SNP可能在CRC的进展和转移中起重要作用。