Abstract
ObjectivePersonalized chemotherapy based on predictive biomarkers can maximize efficacy. However, tumor tissue obtained at the time of initial diagnosis will not reflect genetic alterations observed at the time of disease progression. We have examined whether plasma mRNA levels can be a surrogate for tumor levels in predicting chemosensitivity.MethodsIn 150 gastric cancer patients, mRNA levels of BRCA1 and TS were assessed in plasma and paired tumor tissue. The Mann-Whitney U-test was used to compare mRNA expression levels between tumor samples exhibiting in vitro sensitivity or resistance to docetaxel and pemetrexed. All statistical tests were two-sided.ResultsThere were significant correlations between plasma and tumor mRNA levels of BRCA1 (rho = 0.696, P < 0.001) and TS (rho = 0.620, P < 0.001). BRCA1 levels in plasma (docetaxel-sensitive: 1.25; docetaxel-resistant: 0.50, P < 0.001) and tumor (docetaxel-sensitive: 8.81; docetaxel-resistant: 4.88, P < 0.001) were positively associated with docetaxel sensitivity. TS levels in plasma (pemetrexed-sensitive: 0.90; pemetrexed-resistant: 1.82, P < 0.001) and tumor (pemetrexed-sensitive: 6.56; pemetrexed-resistant: 16.69, P < 0.001) were negatively associated with pemetrexed sensitivity.ConclusionsPlasma mRNA expression levels mirror those in the tumor and may have a promising role as potential predictive biomarkers for chemotherapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-014-0355-2) contains supplementary material, which is available to authorized users.
Highlights
The standard first-line chemotherapy regimen for locally advanced or metastatic gastric cancer is cisplatin or oxaliplatin combined with other drugs, including docetaxel and pemetrexed [1,2]
We have previously observed that Breast cancer susceptibility gene 1 (BRCA1) mRNA levels in effusions were negatively associated with platinum sensitivity but positively associated with docetaxel sensitivity in gastric cancer patients [5]
The mRNA expression levels were stable after room temperature or ice incubation for 30 min, 1h, 1.5 h and 2 h (Additional file 1: Figure S2, available online)
Summary
The standard first-line chemotherapy regimen for locally advanced or metastatic gastric cancer is cisplatin or oxaliplatin combined with other drugs, including docetaxel and pemetrexed [1,2]. Personalized chemotherapy based on the mRNA expression of predictive biomarkers could help to Breast cancer susceptibility gene 1 (BRCA1), an essential component in multiple DNA damage repair pathways and pathways involved in cellular responses to microtubule damage, is considered to be a differential modulator of survival with cisplatin and taxanes. Tumor with high expression of BRCA1 is 800-to-more than 1000-fold sensitive to docetaxel, but 10-1000-fold resistant to cisplatin [4]. We have previously observed that BRCA1 mRNA levels in effusions were negatively associated with platinum sensitivity but positively associated with docetaxel sensitivity in gastric cancer patients [5].
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