RNA-seq reveals determinants of sensitivity to chemotherapy drugs in esophageal carcinoma cells.

Chemotherapy remains the mainstay of treatment for patients with incurable disease of esophageal carcinoma. Most patients respond poorly to chemotherapy, it is necessary to figure out biomarkers for chemotherapy sensitivity or resistance to perform the individualized therapy. In present work, the sensitivities of two ESCC cell lines to 9 chemotherapy drugs were identified and the transcriptome of these two cell lines were investigated by RNA-seq, the correlation between the sensitivity to drugs and expression of some genes was attempted to construct. Eca-1 was more resistant to most of the chemotherapy drugs than Eca-109 cell line. RNA-seq results showed that there is dramatic difference in the basal expression between these two ESCC cell lines. Pathway analysis demonstrated that these differentially expressed genes were mainly enriched in Gαi signaling, calcium signaling, cAMP-mediated signaling, G-protein coupled receptor signaling and actin cytoskeleton signaling pathways. The molecules in Gαi signaling (ADCY1 and SSTR3) and actin cytoskeleton signaling (MYH6 and MYH7) were highly expressed in multidrug-resistant Eca-1 cells, which were validated by quantitative PCR. Activation of these two pathways results in the upregulation of downstream signaling, PKA signaling and Src-STAT3, and downregulation of RAF-ERK signaling, which was validated by immunoblotting experiments. Our work proposed that activation of Gαi signaling or actin cytoskeleton signaling may confer ESCC cells resistance to most chemotherapy drugs. Our work might provide potential biomarkers and therapeutic targets for treatment of EC patients.