Potential biomarkers for sensitivity of gallbladder cancer cells to gemcitabine.

Gemcitabine (Gem)-based chemotherapies are the main therapeutic regimens for patients with unresectable advanced or metastatic gallbladder cancer (GBC). However, the modest ORR and mild benefit on survival demonstrates the need for finding biomarkers for sensitivity to Gem and hence improving the therapy. In present work, two GBC cell lines with vast difference in sensitivity to Gem were subjected to DNA microarray analysis. Dramatic expression difference was found in protein kinase A signaling, P2Y purigenic receptor signaling, ErbB signaling and p70S6K signaling. Predicted low expression of KRAS and inactivation of AKT/ERK signaling in Gem-resistant GBC cells was validated by quantitative PCR and immunoblotting, respectively. However, p70S6K, p38MAPK and NF-κB signaling was probably activated in Gem-resistant GBC cells, which deserves further investigation in more GBC cell lines and tissues. Our work provides potential pathway signatures for Gem sensitivity of GBC patients.