MicroRNA profiling in canine multicentric lymphoma

Abstract

Lymphoma is the most common hematopoietic tumour in dogs and is remarkably similar to the human disease. Tumour biomarker discovery is providing new tools for diagnostics and predicting therapeutic response and clinical outcome. MicroRNAs are small non-coding RNAs that participate in post-transcriptional gene regulation and their aberrant expression can impact genes involved in cancer. The aim of this study was to characterize microRNA expression in lymph nodes and plasma from dogs with multicentric B or T cell lymphoma compared to healthy control dogs. We further compared expression between lymph nodes and corresponding plasma samples and assessed changes in expression at relapse compared to time of diagnosis. Lastly, we investigated microRNAs for association with clinical outcome in patients treated with CHOP chemotherapy. A customized PCR array was utilized to profile 38 canine target microRNAs. Quantification was performed using real time RT-qPCR and relative expression was determined by the delta-delta Ct method. In lymph nodes, there were 16 microRNAs with significantly altered expression for B cell lymphoma and 9 for T cell lymphoma. In plasma, there were 15 microRNAs altered for B cell lymphoma and 3 for T cell lymphoma. The majority of microRNAs did not have correlated expression between lymph node and plasma and only 8 microRNAs were significantly different between diagnosis and relapse. For B cell lymphoma, 8 microRNAs had differential expression in the non-remission group compared to dogs that completed CHOP in complete remission. Four of these microRNAs were also altered in patients that died prior to one-year. Kaplan-Meier survival curves for high versus low microRNA expression revealed that 10 microRNAs were correlated with progression-free survival and 3 with overall survival. This study highlights microRNAs of interest for canine multicentric lymphoma. Future goals include development of microRNA panels that may be useful as biomarkers with the intent to provide improved outcome prediction to veterinary cancer patients.

Liquid biopsy based on small extracellular vesicles predicts chemotherapy response of canine multicentric lymphomas

“…The miR-222 was higher expressed in CR group and was associated with good prognosis. Contradictory results recently published showed miR-222 expression in plasma of dogs with B-cell or T-cell lymphoma was negatively correlated with OS and PFS 23 . The miR-20a was more expressed in CR group and were related to a good prognosis.…”

“…MicroRNAs are small non-coding RNA molecules responsible for post-transcription regulation and can be carried by exosomes regulating important to pathways related to cancer metastasis, prognosis, therapeutic response and chemoresistance mechanisms 20 – 22 . Karlee and collaborators analyzed 38 miRNAs and found altered expression of miR-127, miR-34a and miR125b in plasma comparing dogs with lymphoma that relapsed and healthy control dogs 23 . An in vitro study showed three exosomal miRNAs (miR-151, miR-8908a-3p, and miR-486) and CD82 protein with different expression between vincristine-sensitive canine cancer cell lines (CLBL-1 and GL-1) and the resistant cell line (UL-1) 24 .…”

Intestinal Expression of miR-130b, miR-410b, and miR-98a in Experimental Canine Echinococcosis by Stem-Loop RT-qPCR

“…A couple of studies have been conducted on miR-130b expression in extra-intestinal tissues of dogs. In canine multicentric lymphoma, miR-130b had upregulation and was found correlated with both B and T cell lymphoma (30). In canine uveal melanoma, miR-130b expression was found upregulated in metastasizing tumors, and it was suggested as a potential biomarker to identify the metastasizing disease (31).…”

Epigenetic Mechanisms in Canine Cancer

“…was also differentially expressed in the plasma of dogs with lymphoma (125). Circulating miRNAs detected in the urine are also been detected in canine cancers.…”

“…Furthermore, the same study showed that miR-15a and miR-16 are significantly downregulated in canine ductal carcinomas while miR-181b, -21, -29b, and let-7f showed a significant upregulation in canine tubular papillary carcinomas (120). Thenceforth, some studies have described miRNA profiling in different types of canine cancer such as mast cell tumors (121), osteosarcoma (122), hemangiosarcoma (123), prostate cancer (124), canine multicentric lymphoma (125), and melanoma (126,127). Interestingly, important and welldescribed miRNAs in human cancer including miR-9, miR-18a, miR-126, miR-383, and miR-204 were found to be dysregulated in canine cancer.…”