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Expression and clinical significance of UBE2V1 in cervical cancer.

ABSTRACT: The majority of cervical cancer (CC) patients are caused by the high-risk human papillomavirus (HPV) infection Although they are preventable and controllable, the mortality rate is still high. It is essential to identify the biomarkers for early screening and diagnosis of CC to improve the prognosis of patients with CC. The conjugating enzyme 2 (E2) family members are the key components of ubiquitin protease system. However, the role of E2 family in CC remains unclear. We aimed to investigate the role of UBE2V1, a ubiquitin binding E2 enzyme variant protein (ube2v) without conserved cysteine residues required for E2s catalytic activity in CC. In this study, we first studied the expression of UBE2V1 in CC by real time quantitative PCR (RT-qPCR), and then, the clinical information of 191 CC patients in TCGA database was retrieved to explore the relationship between the expression of UBE2V1 and the occurrence and development of CC by examining the translational profile and methylation, the high expression of UBE2V1 was well correlated to the poor prognosis of patients, indicating that UBE2V1 is an independent risk factor for the prognosis of CC patients. The expression of UBE2V1 was also correlated with clinical stages, tumor grades and TNM stages of CC. In addition, the expression of UBE2V1 was slightly negatively correlated with the methylation at the multiple methylation sites. our study revealed the relationship between UBE2V1 and the occurrence and development of CC from the level of transcriptional profile and DNA methylation. UBE2V1 is a novel candidate biomarker for the diagnosis, screening and prognosis of CC.

SUBMITTER: Ren Z

PROVIDER: S-EPMC8385167 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveCervical cancer is one of the leading fatal diseases in women, and the role of Apolipoprotein B mRNA editing enzyme catalytic subunit 3B (APOBEC3B) in cervical cancer is uncertain.MethodsFour Gene Expression Omnibus (GEO) mRNA microarray datasets were analyzed to identify differentially expressed genes (DEGs) between cervical cancer and normal cervical tissues. The results were validated using a The Cancer Genome Atlas (TCGA)-cervical cancer (CESC) dataset. Expression profiles and patients' clinical data were used to investigate the relationship between APOBEC3B expression and cervical cancer survival. APOBEC3B co-expressed genes were subjected to enrichment analyses, and correlations between APOBEC3B expression and immunologic infiltrates were investigated using Tumor Immune Estimation Resource (TIMER). We generated receiver operating characteristic curve (ROC) curves to evaluate the performance of APOBEC3B expression in predicting cervical cancer prognosis.ResultsFourteen overlapping DEGs were obtained, and APOBEC3B was chosen as a candidate gene. TCGA data further confirmed that APOBEC3B was significantly increased in cervical cancer, relative to normal adjacent tissues, and this expression was associated with poor clinical outcome. Results from quantitative real time polymerase chain reaction (RT-qPCR) and immunohistochemical staining of cervical carcinoma tissues supported these findings. Enrichment analysis showed that APOBEC3B co-expressed genes were mainly enriched in cell cycle, DNA replication and chromosomal region. Moreover, APOBEC3B expression was significantly associated with T stage, M stage, primary therapy outcome and poor clinical prognosis in cervical cancer. Similarly, APOBEC3B was closely correlated with gene markers of diverse immune cells. APOBEC3B expression was an independent indicator of cervical cancer prognosis, according to univariate Cox and ROC analyses.ConclusionHigh APOBEC3B expression is strongly related to a poor prognosis in cervical cancer patients.

Project description:Purpose: This study aimed to identify a novel biomarker or a target of treatment for colorectal cancer (CRC). Experimental Design: The expression profiles of cancer cells in 104 patients with CRC were examined using laser microdissection and oligonucleotide microarray analysis. Overexpression in CRC cells especially in patients with distant metastasis was a prerequisite to select candidate genes. The mRNA expression of candidate gene was investigated by quantitative reversetranscription polymerase chain reaction (RT-PCR) in 77 patients as a validation study. We analyzed the protein expression and localization of the candidate gene by immunohistochemical study, and investigated the relationship between the expression and the clinicopathological feature in 274 CRC patients. Results: We identified 6 genes as candidates related to distant metastasis in CRC patients by microarray analysis. Among these genes, Osteoprotegerin (OPG) is known to have an association with aggressiveness in several cancers through inhibiting apoptosis by neutralizing the function of tumor necrosis factor related apoptosis inducing ligand (TRAIL). The mRNA expression of OPG in cancer tissues was significantly higher in patients with distant metastasis than those without metastasis. The overexpression of OPG protein was significantly associated with worse overall survival and relapse free survival (RFS). Moreover, the overexpression of OPG protein was an independent risk factor for recurrence of CRC. Conclusion: The overexpression of OPG would be a predictive biomarker of recurrence and a target of the treatment for CRC. Total of 148 microarray datasets obtained from LCM and homogenized tissues of colorectal cancer patients were normalized using robust multi-array average (RMA) method under R 2.6.2 statistical software with affy package from BioConductor. Normalization was separately performed for LCM dataset and homogenized tissue dataset. The normalized gene expression levels were presented as log2-transformed values by RMA.

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Expression and clinical significance of UBE2V1 in cervical cancer.

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