Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Osaka, Japan.
Br J Cancer. 2013 Feb 5;108(2):395-401. doi: 10.1038/bjc.2012.572. Epub 2013 Jan 15.
The regenerating gene Iα (REG Iα) is involved in gastric carcinogenesis as an antiapoptotic factor. Therefore, we investigated whether REG Iα confers resistance to chemotherapeutic drugs in gastric cancer (GC) cells and whether REG Iα expression is useful for predicting the response to chemotherapy and outcome in patients with GC.
A total of 70 patients with unresectable stage IV GC received first-line chemotherapy with S-1 and cisplatin (S-1/CDDP). The expression of REG Iα was evaluated immunohistochemically using biopsy samples obtained before chemotherapy, and its relationship to clinicopathological parameters was analysed statistically. The effects of REG Iα gene induction on resistance to 5-FU or CDDP treatment were examined by cell survival assay and flow cytometry.
Of the 70 patients with unresectable stage IV GC, 19 (27%) were positive for REG Iα expression. The expression of REG Iα was independently predictive of poorer progression-free and overall survival in such patients (hazard ratio (HR) 2.46; P=0.002 and HR 1.89; P=0.037, respectively). The gene induction of REG Iα conferred resistance to cell death induced by 5-FU or CDDP in GC cells.
In patients with stage IV GC, REG Iα, which confers resistance to chemotherapeutic drugs in GC cells, is a potential biomarker for predicting resistance to S-1/CDDP treatment.
再生基因 Iα（REG Iα）作为一种抗细胞凋亡因子，参与胃癌的发生。因此，我们研究了 REG Iα 是否使胃癌（GC）细胞对化疗药物产生耐药性，以及 REG Iα 的表达是否有助于预测 GC 患者对化疗的反应和预后。
70 例不可切除的 IV 期 GC 患者接受 S-1 和顺铂（S-1/CDDP）一线化疗。采用免疫组织化学方法检测化疗前活检标本中 REG Iα 的表达，并对其与临床病理参数的关系进行统计学分析。通过细胞存活测定和流式细胞术检测 REG Iα 基因诱导对 5-FU 或 CDDP 治疗耐药的影响。
70 例不可切除的 IV 期 GC 患者中，有 19 例（27%）REG Iα 表达阳性。REG Iα 的表达独立预测此类患者无进展生存期和总生存期较差（风险比（HR）2.46；P=0.002 和 HR 1.89；P=0.037）。REG Iα 的基因诱导使 GC 细胞对 5-FU 或 CDDP 诱导的细胞死亡产生耐药性。
在 IV 期 GC 患者中，REG Iα 可使 GC 细胞对化疗药物产生耐药性，是预测 S-1/CDDP 治疗耐药的潜在生物标志物。
