ABSTRACT
This study aimed to explore the expression and hypermethylation of EPB41L3 and JAM3 in cervical squamous cell carcinoma (CSCC) and to investigate their clinical significance. JAM3 and EPB41L3 mRNA expression was analyzed using a public database, and protein expression was detected using immunohistochemistry. The methylation status of JAM3 and EPB41L3 was detected in CSCC tissues and cervical cytological specimens using a quantitative methylation-specific PCR (qMSP). JAM3 and EPB41L3 mRNA were downregulated in CSCC. The JAM3 protein was positively detected in 39.4% of CSCC tissues and frequently expressed in those with lower FIGO stage and no lymph node metastasis. EPB41L3 was expressed in 18.9% of CSCC tissues. The hypermethylation of JAM3 was detected in 52.3% of CSCC tissues and related to higher FIGO stage and lymph node metastasis. EPB41L3 hypermethylation was detected in 72.7% of CSCC tissues and related to older ages and lymph node metastasis. In cervical cytological specimens, no methylation of JAM3 and EPB41L3 was found in normal or inflamed cervical epithelial cells. The methylation of JAM3 was detected in 0%, 8.3%, and 6.3% of ASCUS, LSIL, and HSIL samples, while EPB41L3 was detected in 12.5%, 42.9%, and 71.4%, respectively. The sensitivity of the combination of JAM3 and EPB41L3 methylation detection in ASCUS, LSIL, and HSIL was 8.3%, 15.6%, and 85.7%, respectively. The specificity of the combination of JAM3 and EPB41L3 methylation detection was 100%. Downregulation of JAM3 and EPB41L3 by hypermethylation was detected in CSCC. JAM3 and EPB41L3 hypermethylation are potential biomarkers for cervical cancer screening.
Subject(s)
Biomarkers, Tumor , Carcinoma, Squamous Cell , Cell Adhesion Molecules , DNA Methylation , Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/metabolism , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/metabolism , Middle Aged , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Cell Adhesion Molecules/genetics , Cell Adhesion Molecules/metabolism , Adult , Lymphatic Metastasis/genetics , Aged , Gene Expression Regulation, Neoplastic , Immunohistochemistry , Clinical Relevance , Microfilament ProteinsABSTRACT
BACKGROUND: Cervical cancer is the most common gynecological cancer, encompassing cervical squamous cell carcinoma, adenocarcinoma, and other epithelial tumors. There are many diagnostic methods to detect cervical cancers but no precision screening tool for cervical adenocarcinoma at present. MATERIAL AND METHODS: The cervical mucus from three normal cervices (Ctrl), three endocervical adenocarcinoma (EA), and three cervical adenocarcinoma in situ (AIS) was collected for proteomic analysis. The proteins were screened using liquid chromatography-mass spectrometry analysis (LC-MS). The biological function of the differently expressed proteins were predicted by Gene Ontology (GO). RESULTS: A total of 711 proteins were identified, including 237 differently expressed proteins identified in EA/Ctrl comparison, 256 differently expressed proteins identified in AIS/Ctrl comparison, and 242 differently expressed proteins identified in AIS/EA comparison (up-regulate ≥ 1.5 or down-regulate ≤ 0.67). Functional annotation was performed using GO analysis on 1,056 differently expressed proteins to identify those that may impact cervical cancer, such as heme protein myeloperoxidase, which is involved in the immune process, and APOA1, which is associated with lipid metabolism. CONCLUSION: We used proteomic analysis to screen out differently expressed proteins from normal cervical mucus and cervical adenocarcinoma mucus samples. These differently expressed proteins may be potential biomarkers for the diagnosis and treatment of cervical adenocarcinoma but require additional study.