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成纤维细胞生长因子受体4第388位密码子的单核苷酸多态性与高级别软组织肉瘤的预后相关。

Single nucleotide polymorphism in fibroblast growth factor receptor 4 at codon 388 is associated with prognosis in high-grade soft tissue sarcoma.

作者信息

Morimoto Yuki, Ozaki Toshifumi, Ouchida Mamoru, Umehara Norifumi, Ohata Norihide, Yoshida Aki, Shimizu Kenji, Inoue Hajime

机构信息

Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.

出版信息

Cancer. 2003 Nov 15;98(10):2245-50. doi: 10.1002/cncr.11778.

DOI:10.1002/cncr.11778
PMID:14601095
Abstract

BACKGROUND

A recent study revealed that single nucleotide polymorphism (SNP) at codon 388 (Gly or Arg) of fibroblast growth factor receptor 4 (FGFR4) was associated with prognosis in patients with carcinoma of the breast and colorectal carcinoma. The purpose of the current study was to investigate the correlation between codon 388 SNP and clinical prognosis in patients with sarcoma of the bone and soft tissues.

METHODS

Tumor samples were obtained from 143 patients with high-grade bone and soft tissue sarcomas at Okayama University Hospital between 1986-2002, and from 102 healthy volunteers. SNP of codon 388 was detected by sequencing and fragment length of polymerase chain reaction products digested by restriction enzyme. The chi-square test was used to compare genotype distribution and the Kaplan-Meier method was used for survival analysis.

RESULTS

With regard to FGFR4 genotypes in the 143 patients studied, 54 (37.8%) were Gly/Gly, 72 (50.3%) were Gly/Arg, and 17 (11.9%) were Arg/Arg, findings that were not significantly different from those of controls (P = 0.97). With regard to cumulative overall and metastasis-free survival, patients with the Gly/Gly genotype were found to have a better prognosis (P = 0.085 and P = 0.27, respectively). FGFR4 SNP was found to be correlated significantly with overall and metastasis-free survival in patients with soft tissue sarcomas (P = 0.029 and P = 0.045, respectively), but not in those patients with bone sarcomas (P = 0.88 and P = 0.75, respectively).

CONCLUSIONS

In the current study, the authors found a significant correlation between FGFR4 SNP and prognosis in patients with soft tissue sarcoma, although the samples were comprised of various histologic types. This SNP might be used to improve the prediction of clinical prognosis and lead to new treatment strategies in patients with soft tissue sarcomas.

摘要

背景

最近一项研究显示,成纤维细胞生长因子受体4(FGFR4)第388密码子(甘氨酸或精氨酸)处的单核苷酸多态性(SNP)与乳腺癌和结直肠癌患者的预后相关。本研究的目的是调查第388密码子SNP与骨和软组织肉瘤患者临床预后之间的相关性。

方法

1986年至2002年间,从冈山大学医院的143例高级别骨和软组织肉瘤患者以及102名健康志愿者中获取肿瘤样本。通过测序检测第388密码子的SNP,并使用限制性内切酶消化聚合酶链反应产物的片段长度。采用卡方检验比较基因型分布,采用Kaplan-Meier法进行生存分析。

结果

在143例研究患者中,FGFR4基因型方面,54例(37.8%)为甘氨酸/甘氨酸型,72例(50.3%)为甘氨酸/精氨酸型,17例(11.9%)为精氨酸/精氨酸型,这些结果与对照组无显著差异(P = 0.97)。在累积总生存率和无转移生存率方面,发现甘氨酸/甘氨酸基因型患者预后较好(分别为P = 0.085和P = 0.27)。发现FGFR4 SNP与软组织肉瘤患者的总生存率和无转移生存率显著相关(分别为P = 0.029和P = 0.045),但与骨肉瘤患者无关(分别为P = 0.88和P = 0.75)。

结论

在本研究中,作者发现FGFR4 SNP与软组织肉瘤患者的预后显著相关,尽管样本包含多种组织学类型。该SNP可能用于改善软组织肉瘤患者临床预后的预测,并带来新的治疗策略。

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