HPV 16 integration is crucial for the onset and progression of premalignant lesions to invasive squamous cell carcinoma (ISCC) because it promotes the amplification of proto-oncogenes and the silencing of tumor suppressor genes; some of these are proteins with PDZ domains involved in homeostasis and cell polarity. Through a bioinformatics approach based on interaction networks, a group of proteins associated with HPV 16 infection, PDZ domains, and direct physical interaction with E6 and related to different hallmarks of cancer were identified. MAGI-1 was selected to evaluate the expression profile and subcellular localization changes in premalignant lesions and ISCC with HPV 16 in an integrated state in cervical cytology; the profile expression of MAGI-1 diminished according to lesion grade. Surprisingly, in cell lines CaSki and SiHa, the protein localization was cytoplasmic and nuclear. In contrast, in histological samples, a change in subcellular localization from the cytoplasm in low-grade squamous intraepithelial lesions (LSIL) to the nucleus in the high-grade squamous intraepithelial lesion (HSIL) was observed; in in situ carcinomas and ISCC, MAGI-1 expression was absent. In conclusion, MAGI-1 expression could be a potential biomarker for distinguishing those cells with normal morphology but with HPV 16 integrated from those showing morphology-related uterine cervical lesions associated with tumor progression.
HPV 16整合对于癌前病变向浸润性鳞状细胞癌（ISCC）的发生和进展至关重要，因为它促进原癌基因的扩增和肿瘤抑制基因的沉默；其中一些是参与稳态和细胞极性的PDZ结构域蛋白。通过基于相互作用网络的生物信息学方法，鉴定出一组与HPV 16感染、PDZ结构域相关，并与E6直接物理相互作用且涉及不同癌症特征的蛋白质。选择MAGI-1来评估宫颈细胞学中处于整合状态的HPV 16相关癌前病变和ISCC的表达谱及亚细胞定位变化；MAGI-1的表达谱随病变级别升高而降低。令人惊讶的是，在CaSki和SiHa细胞系中，该蛋白定位于细胞质和细胞核。相比之下，在组织学样本中观察到亚细胞定位从低级别鳞状上皮内病变（LSIL）的细胞质向高级别鳞状上皮内病变（HSIL）的细胞核转变；在原位癌和ISCC中，MAGI-1表达缺失。总之，MAGI-1表达可能是一种潜在的生物标志物，用于区分形态正常但HPV 16已整合的细胞与表现出与肿瘤进展相关的宫颈病变形态的细胞。
肿瘤(癌症)患者之家