Department of Radiation Biochemistry, A. Tsyb Medical Radiological Research Center-Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, Korolev str.-4, 249036 Obninsk, Russia.
Department of Radiation and Combined Treatment of Gynecological Diseases, A. Tsyb Medical Radiological Research Center, Korolev str.-4, 249036 Obninsk, Russia.
Int J Mol Sci. 2021 Feb 1;22(3):1445. doi: 10.3390/ijms22031445.
Radio- and chemoresistance of cancer stem cells (CSCs) is considered as one of the possible causes of adverse results of chemoradiotherapy for various malignancies, including cervical cancer. However, little is known about quantitative changes in the CSC subpopulation in the course of treatment and mechanisms for individual response of CSCs to therapy. The purpose of the study was to evaluate the association of radiation response of cervical CSCs with clinical and morphological parameters of disease and features of human papillomavirus (HPV) infection. The proportion of CD44CD24 CSCs was determined by flow cytometry in cervical scrapings from 55 patients with squamous cell carcinoma of uterine cervix before treatment and after fractionated irradiation at a total dose of 10 Gy. Real-time PCR assay was used to evaluate molecular parameters of HPV DNA. Post-radiation increase in the CSC proportion was found in 47.3% of patients. Clinical and morphological parameters (stage, status of lymph node involvement, and histological type) were not significantly correlated with radiation changes in the CSC proportion. Single- and multifactor analyses revealed two independent indicators affecting the radiation response of CSCs: initial proportion of CSCs and physical status of HPV DNA (R = 0.86, = 0.001 for the multiple regression model in the whole).
癌症干细胞（CSC）的放射和化学耐药性被认为是各种恶性肿瘤（包括宫颈癌）放化疗不良结果的可能原因之一。然而，对于 CSC 亚群在治疗过程中的定量变化以及 CSC 对治疗的个体反应的机制知之甚少。本研究旨在评估宫颈 CSC 对放射的反应与疾病的临床和形态学参数以及人乳头瘤病毒（HPV）感染特征之间的关联。通过流式细胞术测定 55 例子宫颈鳞状细胞癌患者治疗前和 10Gy 分割照射后的宫颈刮片中 CD44CD24 CSC 的比例。实时 PCR 检测用于评估 HPV DNA 的分子参数。在 47.3%的患者中发现 CSC 比例在放射后增加。临床和形态学参数（分期、淋巴结受累状态和组织学类型）与 CSC 比例的放射变化无显著相关性。单因素和多因素分析显示，两个独立指标影响 CSC 的放射反应：CSC 的初始比例和 HPV DNA 的物理状态（多元回归模型的 R = 0.86，p = 0.001）。
