Transcriptome Signatures of Canine Mammary Gland Tumors and Its Comparison to Human Breast Cancers

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2018 Sep 13

PMID 30205506

Citations 19

Authors

Kang-Hoon Lee

Hyoung-Min Park

Keun-Hong Son

Tae-Jin Shin

Je-Yoel Cho

Affiliations

Soon will be listed here.

Abstract

Breast cancer (BC)/mammary gland carcinoma (MGC) is the most frequently diagnosed and leading cause of cancer-related mortality in both women and canines. To better understand both canine MGC and human BC-specific genes, we sequenced RNAs obtained from eight pairs of carcinomas and adjacent normal tissues in dogs. By comprehensive transcriptome analysis, 351 differentially expressed genes (DEGs) were identified in overall canine MGCs. Based on the DEGs, comparative analysis revealed correlation existing among the three histological subtypes of canine MGC (ductal, simple, and complex) and four molecular subtypes of human BC (HER2+, ER+, ER&HER2+, and TNBC). Eight DEGs shared by all three subtypes of canine MGCs had been previously reported as cancer-associated genes in human studies. Gene ontology and pathway analyses using the identified DEGs revealed that the biological processes of cell proliferation, adhesion, and inflammatory responses are enriched in up-regulated MGC DEGs. In contrast, fatty acid homeostasis and transcription regulation involved in cell fate commitment were down-regulated in MGC DEGs. Moreover, correlations are demonstrated between upstream promoter transcripts and DEGs. Canine MGC- and subtype-enriched gene expression allows us to better understand both human BC and canine MGC, yielding new insight into the development of biomarkers and targets for both diseases.

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References

Terragni R, Casadei Gardini A, Sabattini S, Bettini G, Amadori D, Talamonti C . EGFR, HER-2 and KRAS in canine gastric epithelial tumors: a potential human model?. PLoS One. 2014; 9(1):e85388. PMC: 3893207. DOI: 10.1371/journal.pone.0085388. View

Li J, Sun C, Li W, Chao R, Huang C, Zhou X . Cancer RNA-Seq Nexus: a database of phenotype-specific transcriptome profiling in cancer cells. Nucleic Acids Res. 2015; 44(D1):D944-51. PMC: 4702907. DOI: 10.1093/nar/gkv1282. View

Dobbin Z, Landen C . The importance of the PI3K/AKT/MTOR pathway in the progression of ovarian cancer. Int J Mol Sci. 2013; 14(4):8213-27. PMC: 3645739. DOI: 10.3390/ijms14048213. View

Wang Y, Yao J, Meng H, Yu Z, Wang Z, Yuan X . A novel long non-coding RNA, hypoxia-inducible factor-2α promoter upstream transcript, functions as an inhibitor of osteosarcoma stem cells in vitro. Mol Med Rep. 2014; 11(4):2534-40. PMC: 4337490. DOI: 10.3892/mmr.2014.3024. View

Plasilova M, Hayse B, Killelea B, Horowitz N, Chagpar A, Lannin D . Features of triple-negative breast cancer: Analysis of 38,813 cases from the national cancer database. Medicine (Baltimore). 2016; 95(35):e4614. PMC: 5008562. DOI: 10.1097/MD.0000000000004614. View

Preker P, Almvig K, Christensen M, Valen E, Mapendano C, Sandelin A . PROMoter uPstream Transcripts share characteristics with mRNAs and are produced upstream of all three major types of mammalian promoters. Nucleic Acids Res. 2011; 39(16):7179-93. PMC: 3167610. DOI: 10.1093/nar/gkr370. View

Liu D, Xiong H, Ellis A, Northrup N, Rodriguez Jr C, ORegan R . Molecular homology and difference between spontaneous canine mammary cancer and human breast cancer. Cancer Res. 2014; 74(18):5045-56. PMC: 4167563. DOI: 10.1158/0008-5472.CAN-14-0392. View

Liu J, Shen L, Yao J, Li Y, Wang Y, Chen H . Forkhead box C1 promoter upstream transcript, a novel long non-coding RNA, regulates proliferation and migration in basal-like breast cancer. Mol Med Rep. 2014; 11(4):3155-9. DOI: 10.3892/mmr.2014.3089. View

Kamps R, Brandao R, van den Bosch B, Paulussen A, Xanthoulea S, Blok M . Next-Generation Sequencing in Oncology: Genetic Diagnosis, Risk Prediction and Cancer Classification. Int J Mol Sci. 2017; 18(2). PMC: 5343844. DOI: 10.3390/ijms18020308. View

10.

Lutful Kabir F, Alvarez C, Bird R . Canine Mammary Carcinomas: A Comparative Analysis of Altered Gene Expression. Vet Sci. 2017; 3(1). PMC: 5644615. DOI: 10.3390/vetsci3010001. View

11.

Campos L, Lavalle G, Estrela-Lima A, Melgaco de Faria J, Guimaraes J, Dutra A . CA15.3, CEA and LDH in dogs with malignant mammary tumors. J Vet Intern Med. 2012; 26(6):1383-8. DOI: 10.1111/j.1939-1676.2012.01014.x. View

12.

Sgroi D . Preinvasive breast cancer. Annu Rev Pathol. 2009; 5:193-221. PMC: 3918415. DOI: 10.1146/annurev.pathol.4.110807.092306. View

13.

Vinothini G, Balachandran C, Nagini S . Evaluation of molecular markers in canine mammary tumors: correlation with histological grading. Oncol Res. 2010; 18(5-6):193-201. DOI: 10.3727/096504009x12596189659042. View

14.

Metsalu T, Vilo J . ClustVis: a web tool for visualizing clustering of multivariate data using Principal Component Analysis and heatmap. Nucleic Acids Res. 2015; 43(W1):W566-70. PMC: 4489295. DOI: 10.1093/nar/gkv468. View

15.

Im K, Kim N, Lim H, Kim H, Shin J, Sur J . Analysis of a new histological and molecular-based classification of canine mammary neoplasia. Vet Pathol. 2013; 51(3):549-59. DOI: 10.1177/0300985813498780. View

16.

Jezequel P, Loussouarn D, Guerin-Charbonnel C, Campion L, Vanier A, Gouraud W . Gene-expression molecular subtyping of triple-negative breast cancer tumours: importance of immune response. Breast Cancer Res. 2015; 17:43. PMC: 4389408. DOI: 10.1186/s13058-015-0550-y. View

17.

Hashmi S, Wang Y, Suman D, Parhar R, Collison K, Conca W . Human cancer: is it linked to dysfunctional lipid metabolism?. Biochim Biophys Acta. 2014; 1850(2):352-64. DOI: 10.1016/j.bbagen.2014.11.004. View

18.

Gurda B, Bradbury A, Vite C . Canine and Feline Models of Human Genetic Diseases and Their Contributions to Advancing Clinical Therapies . Yale J Biol Med. 2017; 90(3):417-431. PMC: 5612185. View

19.

Campos M, Kool M, Daminet S, Ducatelle R, Rutteman G, Kooistra H . Upregulation of the PI3K/Akt pathway in the tumorigenesis of canine thyroid carcinoma. J Vet Intern Med. 2014; 28(6):1814-23. PMC: 4895609. DOI: 10.1111/jvim.12435. View

20.

Ejaeidi A, Craft B, Puneky L, Lewis R, Cruse J . Hormone receptor-independent CXCL10 production is associated with the regulation of cellular factors linked to breast cancer progression and metastasis. Exp Mol Pathol. 2015; 99(1):163-72. DOI: 10.1016/j.yexmp.2015.06.002. View