Zheng Hua-Chuan, E Ying, Cui Zheng-Guo, Zhao Shuang, Zhang Yong
Department of Oncology and Experimental Center, The Affiliated Hospital of Chengde Medical University, Chengde, China.
Department of Oncology, Liaoning Cancer Hospital, Shenyang, China.
Front Mol Biosci. 2021 Aug 12;8:687444. doi: 10.3389/fmolb.2021.687444. eCollection 2021.
JC virus (JCV) infects 80-90% of the population and results in progressive multifocal leukoencephalopathy upon immunodeficiency. The study aimed to pathologically clarify the oncogenic roles of T antigen in human breast cancers. Breast cancer, dysplasia, and normal tissues were examined for of JCV by nested and real-time PCR. The positive rate or copy number of T antigen was compared with clinicopathological parameters of breast cancer. JCV existence was morphologically detected by immunohistochemistry and PCR. T antigen was examined by Western blot using frozen samples of breast cancer and paired normal tissues. According to nested PCR, the positive rate of breast ductal or lobular carcinoma was lower than that of normal tissue ( < 0.05). T antigen existence was negatively correlated with E-cadherin expression and triple-negative breast cancer ( < 0.05), but positively correlated with lymph node metastasis and estrogen receptor and progestogen receptor expression ( < 0.05). Quantitative PCR showed that JCV copies were gradually decreased from normal, dysplasia to cancer tissues ( < 0.05). JCV T antigen copy number was lower in ductal adenocarcinoma than in normal tissue ( < 0.05), in line with in situ PCR and immunohistochemistry. JCV copies were negatively correlated with tumor size and E-cadherin expression ( < 0.05), but positively correlated with G grading of breast cancer ( < 0.05). Western blot also indicated weaker T antigen expression in breast cancer than normal tissues ( < 0.05). JCV T antigen might play an important role in breast carcinogenesis. It can be employed as a molecular marker for the differentiation and aggressive behaviors of breast cancer.
JC病毒(JCV)感染80%-90%的人群,在免疫缺陷时会导致进行性多灶性白质脑病。该研究旨在从病理学角度阐明T抗原在人类乳腺癌中的致癌作用。通过巢式PCR和实时PCR检测乳腺癌、发育异常组织和正常组织中的JCV。将T抗原的阳性率或拷贝数与乳腺癌的临床病理参数进行比较。通过免疫组织化学和原位PCR在形态学上检测JCV的存在。使用乳腺癌冰冻样本和配对的正常组织通过蛋白质免疫印迹法检测T抗原。根据巢式PCR,乳腺导管癌或小叶癌的阳性率低于正常组织(P<0.05)。T抗原的存在与E-钙黏蛋白表达和三阴性乳腺癌呈负相关(P<0.05),但与淋巴结转移以及雌激素受体和孕激素受体表达呈正相关(P<0.05)。定量PCR显示,JCV拷贝数从正常组织、发育异常组织到癌组织逐渐减少(P<0.05)。导管腺癌中JCV T抗原拷贝数低于正常组织(P<0.05),与原位PCR和免疫组织化学结果一致。JCV拷贝数与肿瘤大小和E-钙黏蛋白表达呈负相关(P<0.05),但与乳腺癌的G分级呈正相关(P<0.05)。蛋白质免疫印迹法也表明乳腺癌中T抗原的表达比正常组织弱(P<0.05)。JCV T抗原可能在乳腺癌发生过程中起重要作用。它可作为乳腺癌分化和侵袭行为的分子标志物。