Cho Sang Hee, Hong Chang Soo, Kim Hee Nam, Shin Min Ho, Kim Ka Rham, Shim Hyun Jeong, Hwang Jun Eul, Bae Woo Kyun, Chung Ik Joo
Department of Hemato-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Korea.
Department of Preventive Medicine, Chonnam National Medical School, Gwangju, Korea.
Cancer Res Treat. 2017 Jul;49(3):766-777. doi: 10.4143/crt.2016.457. Epub 2016 Nov 9.
Fibroblast growth factor receptor 4 () plays an important role in cancer progression during tumor proliferation, invasion, and metastasis. This study evaluated the prognostic role of polymorphism in patients with resected colon cancer, including the underlying mechanism.
polymorphism was characterized in patientswho received curative resection for stage III colon cancer. -dependent signal pathways involving cell proliferation, invasion, and migration according to genotypes were also evaluated in transfected colon cancer cell lines.
Among a total of 273 patients, the GG of showed significantly better overall survival than the AG or AA, regardless of adjuvant treatment. In the group of AG or AA, combination of folinic acid, fluorouracil, and oxaliplatin (FOLFOX) resulted in better survival than fluorouracil/leucovorin or no adjuvant chemotherapy. However, in GG, there was no difference among treatment regimens. Using multivariate analyses, the Arg388 carriers, together with age, N stage, poor differentiation, absence of a lymphocyte response, and no adjuvant chemotherapy, had a significantly worse OS than patients with the Gly388 allele. In transfected colon cancer cells, overexpression of Arg388 significantly increased cell proliferation and changes in epithelial to mesenchymal transition markers compared with cells overexpressing the Gly388 allele.
The Arg388 allele of may be a biomarker and a candidate target for adjuvant treatment of patients with resected colon cancer.
成纤维细胞生长因子受体4（）在肿瘤增殖、侵袭和转移过程中的癌症进展中起重要作用。本研究评估了多态性在接受结肠癌切除患者中的预后作用，包括其潜在机制。
对接受III期结肠癌根治性切除的患者进行多态性特征分析。还在转染的结肠癌细胞系中根据基因型评估了涉及细胞增殖、侵袭和迁移的依赖信号通路。
在总共273例患者中，无论辅助治疗如何，的GG基因型患者的总生存期明显优于AG或AA基因型患者。在AG或AA组中，亚叶酸、氟尿嘧啶和奥沙利铂联合方案（FOLFOX）的生存效果优于氟尿嘧啶/亚叶酸或无辅助化疗。然而，在GG组中，各治疗方案之间没有差异。通过多因素分析，与携带Gly388等位基因的患者相比，携带Arg388的患者以及年龄、N分期、低分化、无淋巴细胞反应和未接受辅助化疗的患者总生存期明显更差。在转染的结肠癌细胞中，与过表达Gly388等位基因的细胞相比，过表达Arg388显著增加细胞增殖并改变上皮-间质转化标志物。
的Arg388等位基因可能是接受结肠癌切除患者辅助治疗的生物标志物和候选靶点。
