Ovine pulmonary adenocarcinoma (OPA) is a chronic respiratory disease of sheep caused by jaagsiekte sheep retrovirus (JSRV). JSRV infects respiratory epithelial cells and initiates tumor growth. OPA is an important economic and welfare issue for sheep farmers but is also considered to be a valuable animal model for human lung adenocarcinoma. In this study, whole transcriptome profiling was performed on lung samples derived from JSRV-infected and uninfected lambs using RNA-seq.

Ovine pulmonary adenocarcinoma (OPA) is a chronic respiratory disease of sheep caused by jaagsiekte sheep retrovirus (JSRV). JSRV infects respiratory epithelial cells and initiates tumor growth. OPA is an important economic and welfare issue for sheep farmers but is also considered to be a valuable animal model for human lung adenocarcinoma. In this study, we investigated the pathogenesis of OPA at the gene expression level and used the deregulated gene list to tp compare to transcriptional changes occurring in human lung cancer. Whole transcriptome profiling was performed on lung samples derived from JSRV-infected and uninfected lambs using RNA-seq. Following mapping of sequence reads to the sheep genome, differentially expressed genes were identified. A list of 1,971 differentially expressed transcripts was identified between the two groups. The main differentially expressed pathways of the upregulated genes were related to immune response to wound healing, tumorigenesis, epithelial cell differentiation and tissue development. Several genes involved in these biological processes were confirmed with immunohistochemistry and RT-qPCR. Important novel insights include the activation of Hippo signaling in OPA and the upregulation of a family of tyrosine kinase receptor ligands, both of which may have important contributions to oncogenesis in this disease. In addition, a variety of myeloid cell markers were upregulated, reflecting a role for tumor associated macrophgaes in this disease. Pathway and functional annotation analysis was performed using Ingenuity pathway analysis and DAVID annotation software and sheep data were compared with already published data derived from non-small cell lung cancer cases in humans. Many of the upregulated gene have also been shown to play an important role in human lung adenocarcinoma and ??? analysis confirmed the closer similarity of experimental OPA with early stage human lung adenocarcinoma. Sheep lung adenocarcinoma shares important similarities with human lung adenocarcinoma. This analysis provides a great deal of new information regarding the pathogenesis of OPA at a transcriptional level and strengthens the use of this naturally occurring animal model for human lung adenocarcinoma.