Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, No.38 Guangji Rd., Banshanqiao District, Hangzhou, 310022, People's Republic of China.
Dig Dis Sci. 2013 Feb;58(2):414-22. doi: 10.1007/s10620-012-2381-3. Epub 2012 Sep 26.
RegIV, a member of the Regenerating (REG) gene family, may be a marker for the prediction of resistance to 5-fluorouracil (5-FU)-based chemotherapy. However, the relationship between the intrinsic drug resistance of gastric cancer (GC) cells to 5-FU used alone (single FU) or in multidrug therapeutic regimens (5-FU combinations) and RegIV expression has not been investigated.
The patient cohort comprised 45 patients with primary GC. The chemoresistance of GC cells to therapeutic regimens consisting of single 5-FU or FU combinations was investigated using the ATP-tumor chemosensitivity assay. The level of RegIV mRNA transcripts was determined by real-time reverse transcriptase-PCR. RegIV expression was evaluated as a novel predictive biomarker for the intrinsic drug resistance of primary GC cells to single 5-FU or 5-FU combinations.
Upregulation of RegIV mRNA transcripts was observed in 36 of the 45 tumor specimens and was positively correlated with the invasive depth of the tumor cells (p = 0.000), the clinical stages (p = 0.000) and the in vitro intrinsic drug resistance of primary GC cells to 5-FU (p = 0.000) or 5-FU combinations.
RegIV mRNA transcript level was strongly associated with the intrinsic resistance of GC cells to single 5-FU or 5-FU combinations, suggesting that RegIV may play an important role in the intrinsic resistance of GC cells to 5-FU and that targeted therapy against the RegIV gene could be applied to overcome 5-FU resistance in the treatment of GC.
RegIV 是再生（REG）基因家族的成员，可能是预测对基于 5-氟尿嘧啶（5-FU）的化疗耐药的标志物。然而，胃癌（GC）细胞对单独使用 5-FU（单 FU）或多药治疗方案（5-FU 联合）的内在药物耐药性与 RegIV 表达之间的关系尚未得到研究。
患者队列包括 45 名原发性 GC 患者。使用 ATP-肿瘤化疗敏感性测定法研究 GC 细胞对包含单 5-FU 或 FU 联合的治疗方案的化疗耐药性。通过实时逆转录-PCR 测定 RegIV mRNA 转录物的水平。RegIV 表达被评估为原发性 GC 细胞对单 5-FU 或 5-FU 联合的内在药物耐药性的新型预测生物标志物。
在 45 个肿瘤标本中观察到 RegIV mRNA 转录物的上调，并且与肿瘤细胞的浸润深度呈正相关（p = 0.000），与临床分期呈正相关（p = 0.000），与原发性 GC 细胞对 5-FU（p = 0.000）或 5-FU 联合的内在药物耐药性呈正相关。
RegIV mRNA 转录物水平与 GC 细胞对单 5-FU 或 5-FU 联合的内在耐药性密切相关，表明 RegIV 可能在 GC 细胞对 5-FU 的内在耐药性中发挥重要作用，针对 RegIV 基因的靶向治疗可能应用于克服 GC 治疗中的 5-FU 耐药性。
