Tumor Treating Fields selectively inhibits the cell cycle and induce apoptosis in human mesothelioma cell lines

The RNA from well characterized human mesothelioma cell lines, namely CD473 and CD60, representative of the epithelioid and the sarcomatoid subtypes, respectively, was sequenced in order to investigate the transcriptional changes induced by the treatment with Tumor treating Fields (TTF). Briefly, for both cell lines, samples were taken under untreated condition and after different time of exposure to TTF, such as 8, 24 and 48 hours after treatment. For each condition, three biological replicates were analyzed. RNA-Seq results showed that TTF induced a transcriptional response already detectable at the first time point (8 hours). With the highest transcriptional changes, the epithelioid cell line, CD473, showed high sensitivity to the treatment in comparison to the sarcomatoid, CD60. Differentially expressed genes were involved in several pathways, such as those of cell cycle checkpoint, DNA repair and histone modifications. These results suggest a preferential activity of TTF in the epithelioid subtype being of clinical importance for the selection of patients that could benefit from this treatment.