Laboratorio de Oncología Genómica, Unidad de Investigación Médica en Enfermedades Oncológicas, Hospital de Oncología, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México.
Unidad de Investigación en Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, México.
Arch Med Res. 2020 Aug;51(6):504-514. doi: 10.1016/j.arcmed.2020.05.025. Epub 2020 Jun 13.
Cervical Cancer (CC) is a worldwide public health concern associated with genetic alterations, among these the gain of the 19q chromosome harboring the Pregnancy Specific Glycoproteins (PSG) gene family. These proteins play a critical role in pregnancy, with participation in immunotolerance, angiogenesis, and invasion processes, which are also observed in carcinogenesis. The aim of this study was to determine the molecular alterations of PSG1 and its relationship with CC.
PSG1 Copy Number Variation (CNV) was evaluated in 31 CC and eight normal cervical tissues by qPCR. PSG1 expression was correlated with HPV detection and IL-10 and TGF-β expression in CC samples. Finally, PSG1 protein expression was evaluated by immunofluorescence in CC cell lines, by immunohistochemistry in a tissue microarray, and by immunoblotting in the sera of women with normal cervix, pre-invasive lesions, and CC.
PSG1 showed a gain of 25.6% in CNV and gene expression in CC. There was a lack of PSG1 expression in normal cervical epithelium and positive immunostaining in 57% of CC tissues, while all CC cell lines expressed PSG1. Finally, PSG1 was immunodetected in 90% of pre-invasive lesions and in all CC serum samples, but not in healthy women. PSG1 expression correlates with the expression of IL-10 and TGF-β in CC tissues, but not with the presence of HPV.
These data show evidence of the differential expression of PSG1 in CC that could explain its participation in tumor-biology and immunotolerance mechanisms. Further, its immunodetection could provide early detection of this cancer.
宫颈癌（CC）是一个全球性的公共卫生问题，与遗传改变有关，其中包括 19q 染色体的获得，该染色体携带有妊娠特异性糖蛋白（PSG）基因家族。这些蛋白在妊娠中起着至关重要的作用，参与免疫耐受、血管生成和侵袭过程，这些过程也发生在癌变中。本研究的目的是确定 PSG1 的分子改变及其与 CC 的关系。
通过 qPCR 评估 31 例 CC 和 8 例正常宫颈组织中的 PSG1 拷贝数变异（CNV）。PSG1 表达与 CC 样本中的 HPV 检测以及 IL-10 和 TGF-β表达相关。最后，通过免疫荧光在 CC 细胞系中、组织微阵列中的免疫组化和正常宫颈、癌前病变和 CC 妇女血清中的免疫印迹评估 PSG1 蛋白表达。
PSG1 在 CNV 和 CC 中的基因表达中显示出 25.6%的增益。正常宫颈上皮中缺乏 PSG1 表达，而 57%的 CC 组织中存在阳性免疫染色，而所有 CC 细胞系均表达 PSG1。最后，PSG1 在 90%的癌前病变和所有 CC 血清样本中均被免疫检测到，但在健康女性中未检测到。PSG1 表达与 CC 组织中 IL-10 和 TGF-β的表达相关，但与 HPV 的存在无关。
这些数据表明 PSG1 在 CC 中的差异表达提供了其参与肿瘤生物学和免疫耐受机制的证据。此外，其免疫检测可能为这种癌症的早期检测提供依据。
