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Enhanced RegIV Expression Predicts the Intrinsic 5-Fluorouracil (5-FU) Resistance in Advanced Gastric Cancer

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Abstract

Aim

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.

Methods

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.

Results

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.

Conclusion

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.

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Acknowledgments

This research was partly supported by a grant from the Science and Technology General Project of Zhejiang Province (No. 2009C33143) and a grant from the Science and Technology Plan Projects of Zhejiang Provincial Medicine and Health (2009B029).

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Correspondence to Zhi-Qiang Ling.

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Ying, LS., Yu, JL., Lu, XX. et al. Enhanced RegIV Expression Predicts the Intrinsic 5-Fluorouracil (5-FU) Resistance in Advanced Gastric Cancer. Dig Dis Sci 58, 414–422 (2013). https://doi.org/10.1007/s10620-012-2381-3

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  • DOI: https://doi.org/10.1007/s10620-012-2381-3

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