Plasma mRNA as liquid biopsy predicts chemo-sensitivity in advanced gastric cancer patients.

Predictive biomarkers based individualized chemotherapy can improve efficacy. However, for those advanced patients, it may be impossible to obtain the tissues from operation. Tissues from biopsy may not be always enough for gene detection. Thus, biomarker from blood could be a non-invasive and useful tool to provide real-time information in the procedure of treatment. To further understand the role of plasma mRNA in chemo-efficiency prediction, several mRNA expression levels were assessed in plasma and paired tumor tissues from 133 locally advanced gastric cancer patients (stage III), and mRNA levels were correlated with chemosensitivity to docetaxel, pemetrexed, platinum, and irinotecan. mRNA expression level in 64 advanced gastric cancer patients (stage IV) was also examined (55 in test group, and 9 in control), and chemotherapy in the test group were given according to the plasma gene detection. As a result, in the 133 patients with locally advanced gastric cancer (Stage III), correlations were observed between the mRNA expression of plasma/tumor BRCA1 levels and docetaxel sensitivity (P<0.001), plasma/tumor TS and pemetrexed sensitivity (P<0.001), plasma/tumor BRCA1 and platinum sensitivity (plasma, P=0.016; tumor, P<0.001), and plasma/tumor TOPO1 and irinotecan sensitivity (plasma, P=0.015; tumor, P=0.011). Among another 64 patients with advanced cancer (Stage IV), the median OS of test group was 15.5m (95% CI=10.1 to 20.9m), the PFS was 9.1m (95% CI=8.0 to 10.2m), which were significant longer than the control (P=0.047 for OS, P=0.038 for PFS). The mortality risk was higher in the control than patients treated according to the plasma gene detection (HR in the control=2.34, 95% CI=0.93 to 5.88, P=0.071). Plasma mRNA as liquid biopsy could be ideal recourse for examination to predict chemo-sensitivity in gastric cancer.