Affiliations: [a] Genetics and Molecular Medicine Department, Zanjan University of Medical Science, Zanjan, Iran | [b] Molecular Biotechnology Department, Pasteur Institute of Iran, Tehran, Iran | [c] ATMP Department, Breast Cancer Research Center, Motamed Cancer Institute, Tehran, Iran | [d] Virology Department, School of Public Health, Tehran University of Medical Science, Tehran, Iran | [e] Virology Department, Pasteur Institute of Iran, Tehran, Iran
Correspondence:
[*]
Corresponding authors: Alireza Biglari, Genetics and
Molecular Medicine Department, Zanjan University of Medical Science, Zanjan, Iran.
E-mail: abiglari@sina.tums.ac.ir. https://orcid.org/0000-0002-3020-5889. Kayhan Azadmanesh,
Virology Department, Pasteur Institute of Iran, Tehran, Iran. E-mail:
azadmanesh@pasteur.ac.ir. https://orcid.org/0000-0002-7165-9043.
Abstract: Breast cancer is the most common malignancy in women worldwide. Administration of oncolytic viruses is one of the novel promising cancer therapy approaches. Replication of these viruses is usually limited to cancer cells that have interferon (IFN) signaling defects. However, Interferon signaling is not completely impaired in all cancer cells which may limit the benefits of virotherapy. Identification of realistic IFN-mediated biomarkers to identify patients who most likely respond to virotherapy would be helpful. In this study, eight patients-derived primary tumor cultures were infected with an ICP34.5 deleted oHSV, then the rate of infectivity, cell survival, and expression of the gene involved in IFN pathway were analyzed. Data showed that mRNA expressions of Myeloid differentiation primary response protein (Myd88) is significantly higher in tumors whose primary cultures showed less cell death and resistance to oHSV infectivity (P-value < 0.05). The differentiating cut off of Myd88 expression, inferred from the receiver operating characteristic (ROC) curve, predicted that only 13 out of 16 other patients could be sensitive to this oHSV. Identifying such biomarker improves our ability to select the patients who do not exhibit resistance to virotherapy.
Keywords: Breast cancer, primary tissue culture, oncolytic virus, resistance to virotherapy, oncolytic herpes simplex virus type 1 (oHSV-1), gene expression, interferon pathway, and MyD88 gene
