Nejatipour Zahra, Teimoori-Toolabi Ladan, Forooshani Ramin Sarrami, Barough Mahdieh Shokrollahi, Farahmand Mohammad, Biglari Alireza, Azadmanesh Kayhan
Genetics and Molecular Medicine Department, Zanjan University of Medical Science, Zanjan, Iran.
Molecular Biotechnology Department, Pasteur Institute of Iran, Tehran, Iran.
Cancer Biomark. 2023;38(1):37-47. doi: 10.3233/CBM-230033.
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.
乳腺癌是全球女性中最常见的恶性肿瘤。溶瘤病毒给药是一种新型且有前景的癌症治疗方法。这些病毒的复制通常局限于具有干扰素（IFN）信号缺陷的癌细胞。然而，并非所有癌细胞中的干扰素信号都完全受损，这可能会限制病毒疗法的益处。识别现实的IFN介导的生物标志物以确定最有可能对病毒疗法产生反应的患者将有所帮助。在本研究中，用缺失ICP34.5的oHSV感染了8例患者来源的原发性肿瘤培养物，然后分析了感染率、细胞存活率以及IFN途径相关基因的表达。数据显示，在原发性培养物显示较少细胞死亡且对oHSV感染具有抗性的肿瘤中，髓样分化初级反应蛋白（Myd88）的mRNA表达显著更高（P值<0.05）。根据受试者工作特征（ROC）曲线推断的Myd88表达的区分阈值预测，其他16例患者中只有13例可能对这种oHSV敏感。识别此类生物标志物可提高我们选择对病毒疗法无抗性患者的能力。
