触珠蛋白对化疗药物吉西他滨血液学毒性的预测

Prediction of haptoglobin on hematologic toxicities of gemcitabine

目的晚期胰腺癌的标准治疗是吉西他滨单药治疗，然而严重的中性粒细胞和血小板减少有时可以威胁患者生命。本研究的目的是寻找一种新方法以预测吉西他滨引起的血液学毒性。方法利用量化质谱（MS）比较使用吉西他滨化疗2个周期发生严重血液学毒性的20例患者（3～4级的中性粒细胞减少或2—4级血小板减少等）和20例没有发生血液学毒性患者（0级）的蛋白组学。结果在60，888肽中757肽峰密度明显不同（P〈0．01），差异有统计学意义（P=0．00003）的质谱高峰来源于触珠蛋白。结论尽管触珠蛋白和血液学毒性之间的确切机制还需要进一步证实，但该研究对接受吉西他滨治疗的患者有较高的实用价值。

Objective Gemcitabine monotherapy is the current standard for patients with ad- vanced pancreatic cancer, but the occurrence of severe neutropenia and thrombocytopenia can sometimes be life threatening. This study aimed to discover a new diagnostic method for predicting the hematologic toxicities of gemcitabine. Methods Using quantitative mass spectrometry （ MS）, we compared the baseline plasma proteomes of 20 patients who had developed severe hematologic adverse events （ grade 3 to 4 neutropenia and/or grade 2 to 4 thrombocytopenia） within the first two cycles of gemcitabine with those of 20 patients who had not （ grade 0）. Results Seven hundred and fifty - seven peptide peaks were iden- tified, whose intensities were significantly different （ P 〈 0.01 ） among a total of 60,888. The MS peak with the highest statistical significance （ P = 0. 00003 ） was derived from haptoglobin by tandem MS. Conclusions Although the precise mechanism responsible for the correlation of haptoglobin with the future onset of hematologic toxicities remains to be clarified, our prediction model seems to have high practical utility for tailoring the treatment of patients receiving gemcitabine.