Journal

Genetic Testing and Molecular Biomarkers

Papers (20)

Overexpression of Fatty Acid 2-Hydroxylase is Associated with an Increased Sensitivity to Cisplatin by Ovarian Cancer and Better Prognoses

Background: Recent discoveries indicate that the enzyme fatty acid 2-hydroxylase (FA2H) is associated with biological behavior and can be used for outcome prediction in several types of cancers. Such relevancy, however, between FA2H and ovarian cancer is not clear. Therefore, we carried out this study to compare the expression of FA2H with the clinicopathological features of ovarian cancer. Methods: Using the Oncomine database, we examined the expression levels of the FA2H gene in ovarian cancer tissues and their adjacent noncancerous tissues that had been evaluated by quantitative reverse-transcription polymerase chain reaction (PCR) analyses. We performed Kaplan-Meier curve analyses for overall survival and progression-free survival. In addition, relationships between the FA2H expression levels and clinicopathological features of ovarian cancer were analyzed. Finally, FA2H small interfering RNAs (siRNAs) or negative control siRNAs were separately transfected into OVCAR-3 and SKOV-3 cells to explore the downstream effects. From these results, Gli1 expression was tested by real-time PCR, and the effects of FA2H expression levels on the sensitivity of ovarian cancer cells to cisplatin chemotherapy was evaluated using sulforhodamine B assays. Results: Compared with the adjacent tissues, FA2H was expressed at lower levels in the ovarian cancer tissues. In survival analyses, decreased FA2H was significantly associated with poorer survival outcome in multiple subtypes of ovarian cancer. In addition, FA2H expression was significantly associated with Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage, differentiation, lymph node involvement, tumor size, ascites, CA125 levels, and pelvic involvement. Knockdown of FA2H expression by siRNAs in the OVCAR-3 and SKOV-3 cell lines reduced their sensitivity to cisplatin, via modulation of GLI Family Zinc Finger 1 ( Gli1 ) gene expression. Conclusion: Our results demonstrate that FA2H is a biomarker for ovarian cancer and it may serve as a useful prognostic factor.

A Novel Prognostic Model of Endometrial Cancer Based on Inflammation and Lipid Metabolism Genes

Background: Endometrial cancer (EC) is a malignancy of the inner epithelial lining of the uterus, with an increasing incidence and disease-associated mortality worldwide. Inflammation and lipid metabolism contribute to EC risk. Materials and Methods: Differential expression genes (DEGs) in EC and normal samples were analyzed based on the TCGA-UCEC database, and DEGs associated with inflammation and lipid metabolism were screened out to be candidate genes. Prognosis-related genes were analyzed using Cox regression and LASSO regression, and a prognostic model was established. Receiver operating characteristic curves and Kaplan–Meier survival analysis were performed to assess the predictive performance of the prognostic model. Gene Set enrichment analysis, immune infiltration analysis, and gene set variation analysis were performed. Expression of prognostic genes in local tissues was examined by Reverse Transcription Quantitative PCR (RT-qPCR) and immunohistochemistry. Methylthiazolyldiphenyl-tetrazolium bromide assay, migration assay, and wound-healing assay were applied to examine the role of CKMT1B on cell proliferation and migration in EC cell lines. Results: A prognostic model based on six prognosis-related genes (CKMT1B, NTS, NSG2, H3C1, MAL, ELOA2) was established in EC, and this model had a favorable predictive performance. Respective different pathways and immune cell infiltration were associated with prognostic genes. 5/6 prognostic genes were highly expressed in local EC tissues compared with normal tissues. Knockdown of CKMT1B significantly suppressed cell proliferation and metastasis in EC cell lines. Conclusion: CKMT1B, NTS, NSG2, H3C1, MAL, and ELOA2 (especially CKMT1B) were important factors in human EC and could be potentially used for risk stratification and prognosis prediction in EC.

The Role of CADM1 and MAL Promoter Methylation in Inflammation and Cervical Intraepithelial Neoplasia

Aims: This study investigated the presence of human papillomavirus (HPV) infection and the methylation status of the promoters of the cell adhesion molecule 1 ( CADM1 ) gene and T lymphocyte maturation associated protein ( MAL ) gene in patients with cervicitis/inflammation and cervical intraepithelial neoplasia (CIN). Materials and Methods: Cervical specimens ( n  = 47) were collected from women with normal cervical cytology ( n  = 21) and those with cervical abnormalities ( n  = 26). The presence of HPV infection was confirmed by an HPV DNA test and an HPV mRNA test (Aptima HPV test). Methylation levels of the CADM1 and MAL promoters were evaluated by pyrosequencing. Results: Compared with the HPV DNA test, the Aptima HPV test improved specificity from 57% to 70% for the detection of inflammation and/or CIN type 1 (CIN1) or more advanced conditions (CIN1+). The methylation level of the CADM1 and MAL promoters was 1.5 times higher in inflammatory samples, compared with normal cervical cytology ( p  < 0.05). Conclusion: Selected 5′-C-phosphate-G-3′ islands within the promoters of the CADM1 and MAL genes were differentially methylated in the inflammatory samples compared with the CIN samples. These results suggested that methylation likely occurred following tissue disruption, and the detection of persistent inflammation might be associated with a higher risk of lesion progression.

Clinical Significance and Prognostic Value of Lactate Dehydrogenase Expression in Cervical Cancer

Background: Lactate dehydrogenase (LDH) is a marker of injury and disease as it is expressed extensively in numerous cell types and tissues. Moreover it is released during tissue breakdown, and is elevated in cancerous tissues. However, the clinical significance and prognostic value of LDH as a tumor marker have been subject to considerable discussion. Objective: In this study, clinical serum LDH data from patients with cervical cancer (CC), CC microarray data, and RNA-seq data were integrated to assess the expression of LDH in CC. Methods: A total of 204 patients with newly diagnosed CC and 204 age-matched healthy controls were included to evaluate serum LDH levels in CC and non-cancer samples. External microarrays and RNA-seq datasets were collected for the differential expression analysis of LDH in CC and non-cancer tissue samples. Kaplan-Meier survival curves of the prognostic value of LDH for CC were plotted for RNA-seq data. Functional enrichment analysis was performed for the genes co-expressed with LDH. Results: The data from our in-house clinical cases as well as the data extracted from microarrays and RNA-seq databases demonstrated significant overexpression of LDH in CC samples. Elevated LDH expression levels were associated with poor overall survival in CC patients. The genes co-expressed with LDH were significantly correlated with the biological processes and pathways, associated with nuclear division, the condensed chromosome, protein serine/threonine kinase activity, and the cell cycle. Conclusion: In conclusion, LDH upregulation might serve as a therapeutic and prognostic biomarker for CC.

Publisher

SAGE Publications

ISSN

1945-0265