RESUMEN
Cervical cancer (CC) is one of the most common malignant tumors. This study analyzed the impact of protein tyrosine phosphatase, receptor type B (PTPRB) on malignant behavior of CC and explored its possible molecular mechanism. RT-PCR, western blot and Immunohistochemistry were applied to examine the expression of PTPRB in CC specimens and cells. Aberrant PTPRB expression in CC and survival outcomes were constructed using The Cancer Genome Atlas (TCGA) database and tissue microarray cervical squamous cell carcinoma cohort. Cultured human CC cells were assayed for viability, apoptosis, migration, and invasion in vitro and in vivo. Kyoto Encyclopedia of Genes and Genomes (KEGG) assays and gene set enrichment analysis (GSEA) assays were used to delve into PTPRB-related pathways using TCGA datasets. The levels of proteins associated with the epithelial-mesenchymal transition (EMT) pathway and modulated by PTPRB were examined through Western blot. We found that the levels of PTPRB in CC tissues and cells were distinctly up-regulated. PTPRB was also an unfavorable prognostic factor for CC patients. Functionally, PTPRB knockdown exhibits tumor-suppressive function via reducing cell proliferation and metastasis and inducing cell apoptosis. KEGG assays and GSEA assays suggested PTPRB overexpression was associated with several tumor-related pathways. The results of Western blot assays suggested that N-cadherin was decreased in the PTPRB-knockdown CC cells, while E-cadherin was increased. Overall, PTPRB is highly expressed in CC and can effectively enhance the proliferation, metastasis and EMT process of tumor cells. PTPRB is expected to be a therapeutic target for CC.
Asunto(s)
Biomarcadores de Tumor/genética , Transición Epitelial-Mesenquimal/genética , Proteínas Tirosina Fosfatasas Clase 3 Similares a Receptores/genética , Neoplasias del Cuello Uterino , Biomarcadores de Tumor/metabolismo , Bases de Datos Genéticas , Femenino , Humanos , Metástasis de la Neoplasia , Proteínas Tirosina Fosfatasas Clase 3 Similares a Receptores/metabolismo , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patologíaRESUMEN
AIM: Villoglandular adenocarcinoma (VGA) of the uterine cervix is a variant of endocervical adenocarcinoma. However, the clinicopathologic and immunohistochemical features of VGA are still unclear. The aim of this study was to investigate the clinicopathologic and immunohistochemical features of VGA. MATERIALS AND METHODS: A total of 20 VGA patients were identified among 852 patients diagnosed with cervical cancer and enrolled in this study. The immunohistochemical levels of Ki-67, P53, P16, progesterone receptor (PR), carcinoembryonic antigen (CEA), vimentin (Vim), and estrogen receptor (ER) were measured by immunohistochemistry. RESULTS: VGA was prevalent in younger women and presented favorable prognosis. Ki-67, P16, and CEA were highly expressed in VGA tissues, while PR expression was hardly to be detected. The positive rates of Ki-67, CEA, and P16 were 90.0%, 90.0%, and 85.0%, respectively, which were significantly higher compared with PR (5.0%, P < 0.001). In addition, the positive rates of P53, Vim, and ER in VGA tissues were 55.0%, 50.0%, and 40.0%, respectively. However, the expression levels of Ki-67, P53, P16, PR, CEA, Vim, and ER were not significantly associated with clinical features (P > 0.05). CONCLUSION: These data indicate that VGA is a rare cervical adenocarcinoma, which is prevalent in younger women, and presents favorable prognosis. Detection of Ki-67, P53, P16, PR, CEA, Vim, and ER would be beneficial for the diagnosis of VGA.