Factor Analysis for Bicluster Acquisition (FABIA) revealed vincristine-sensitive transcript pattern of canine transmissible venereal tumors

Abstract

Chemotherapeutic treatment for Canine transmissible venereal tumor (CTVT) commonly relies on vincristine administration. Since the treatment outcomes can vary among CTVT cases, gaining insight into the tumor cell mechanisms influencing vincristine's potency should render veterinarians novel knowledge to enhance its therapeutic effect. This study aimed to attain such knowledge from a meta-analysis of CTVT mRNA sequencing (mRNA-seq) transcriptome data using Factor Analysis for Bicluster Acquisition (FABIA) biclustering.FABIA biclustering identified 459 genes consistently expressed among mRNA-seq transcription profiling of CTVT samples regressed by vincristine. These genes were also differentially expressed from those of progressive CTVT (FDR ≤ 0.001). Enrichment analysis illustrated the affiliation of these genes with “Antigen presentation” and “Lysosome” GO terms (FDR ≤ 0.05). Several genes in “Lysosome” term involved 5 cell mechanisms—antigen presentation, autophagy, cell-adhesion, lysosomal membrane permeabilization (LMP), and PI3K/mTOR signaling. This study integrated FABIA biclustering in CTVT transcriptome analysis to gain insight into cell mechanisms responsible for vincristine-sensitive characteristics of the tumor, in order to identify new molecular targets augmenting therapeutic effect of vincristine. Interestingly, the analysis indicated LMP targeting by lysosome destabilizing agent—siramesine as the promising vincristine's enhancer for future study. As far as we know, this is the first canine tumor transcriptomic meta-analysis applying FABIA biclustering for the betterment of future CTVT therapy. This study hereby provided an interesting manifestation to acquire such knowledge in other canine neoplasia.

Keywords

• Cell biology
• Immunology