Reg IV is a serum biomarker for gastric cancer patients and predicts response to 5-fluorouracil-based chemotherapy
Reg IV is a serum biomarker for gastric cancer patients and predicts response to 5-fluorouracil-based chemotherapy
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DOI：
10.1038/sj.onc.1210215
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发表时间：
2007-06-01
期刊：
影响因子：
8
通讯作者：
Yasui, W.
中科院分区：
文献类型：
--
作者：
Mitani, Y.;Oue, N.;Yasui, W.
再生基因家族成员 4 (Reg IV) 是一种分泌蛋白，在多种癌症中过度表达，包括胃癌 (GC)。在本研究中，我们通过酶联免疫吸附测定测量了 GC 患者血清中的 Reg IV 水平。我们还检测了强制Reg IV表达对5-氟尿嘧啶(5-FU)细胞凋亡敏感性的影响。 Reg IV 的强制表达抑制 5-FU 诱导的细胞凋亡。 Bcl-2 和二氢嘧啶脱氢酶的诱导参与细胞凋亡的抑制。在接受低剂量 5-FU 和顺铂联合化疗的 36 名 GC 患者中，所有 14 名 Reg IV 阳性患者均未表现出任何变化或疾病进展。健康个体的血清 Reg IV 浓度平均值 +/- s.e (0.52 +/- 0.05 ng/ml) 与慢性活动性胃炎患者 (0.36 +/- 0.09 ng/ml) 相似。然而，术前 GC 患者的血清 Reg IV 浓度是显着的。即使在 I 期，也明显升高 (1.96 +/- 0.17 ng/ml)。血清 Reg IV 的诊断敏感性 (36.1%) 优于血清癌胚抗原 (11.5%) 或碳水化合物抗原 19-9 (13.1%)。这些结果表明，Reg IV 的表达是预测 GC 患者对基于 5-FU 的化疗耐药的标志物。 Serum Reg IV 代表了 GC 的一种新型生物标志物。
Regenerating gene family, member 4 (Reg IV), a secreted protein, is overexpressed in several cancers, including gastric cancer (GC). In the present study, we measured Reg IV levels in sera from patients with GC by enzyme-linked immunosorbent assay. We also examined the effect of forced Reg IV expression on the apoptotic susceptibility to 5-fluorouracil(5-FU). Forced expression of Reg IV inhibited 5-FU-induced apoptosis. Induction of Bcl-2 and dihydropyrimidine dehydrogenase was involved in inhibition of apoptosis. Among 36 GC patients treated with a combination chemotherapy of low-dose 5-FU and cisplatin, all 14 Reg IV-positive patients showed no change or disease progression. The serum Reg IV concentration was similar between healthy individuals mean +/- s.e., (0.52 +/- 0.05 ng/ml) and patients with chronic-active gastritis (0.36 +/- 0.09 ng/ml). However, the serum Reg IV concentration in presurgical GC patients was signifi. cantly elevated (1.96 +/- 0.17 ng/ml), even at stage I. The diagnostic sensitivity of serum Reg IV (36.1%) was superior to that of serum carcinoembryonic antigen (11.5%) or carbohydrate antigen 19-9 (13.1%). These results indicate that expression of Reg IV is a marker for prediction of resistance to 5-FU-based chemotherapy in patients with GC. Serum Reg IV represents a novel biomarker for GC.