Identification of differentially expressed genes using an annealing control primer system in stage III serous ovarian carcinoma

Abstract

BackgroundMost patients with ovarian cancer are diagnosed with advanced stage disease (i.e., stage III-IV), which is associated with a poor prognosis. Differentially expressed genes (DEGs) in stage III serous ovarian carcinoma compared to normal tissue were screened by a new differential display method, the annealing control primer (ACP) system. The potential targets for markers that could be used for diagnosis and prognosis, for stage III serous ovarian cancer, were found by cluster and survival analysis.MethodsThe ACP-based reverse transcriptase polymerase chain reaction (RT PCR) technique was used to identify DEGs in patients with stage III serous ovarian carcinoma. The DEGs identified by the ACP system were confirmed by quantitative real-time PCR. Cluster analysis was performed on the basis of the expression profile produced by quantitative real-time PCR and survival analysis was carried out by the Kaplan-Meier method and Cox proportional hazards multivariate model; the results of gene expression were compared between chemo-resistant and chemo-sensitive groups.ResultsA total of 114 DEGs were identified by the ACP-based RT PCR technique among patients with stage III serous ovarian carcinoma. The DEGs associated with an apoptosis inhibitory process tended to be up-regulated clones while the DEGs associated with immune response tended to be down-regulated clones. Cluster analysis of the gene expression profile obtained by quantitative real-time PCR revealed two contrasting groups of DEGs. That is, a group of genes including: SSBP1, IFI6 DDT, IFI27, C11orf92, NFKBIA, TNXB, NEAT1 and TFG were up-regulated while another group of genes consisting of: LAMB2, XRCC6, MEF2C, RBM5, FOXP1, NUDCP2, LGALS3, TMEM185A, and C1S were down-regulated in most patients. Survival analysis revealed that the up-regulated genes such as DDAH2, RNase K and TCEAL2 might be associated with a poor prognosis. Furthermore, the prognosis of patients with chemo-resistance was predicted to be very poor when genes such as RNase K, FOXP1, LAMB2 and MRVI1 were up-regulated.ConclusionThe DEGs in patients with stage III serous ovarian cancer were successfully and reliably identified by the ACP-based RT PCR technique. The DEGs identified in this study might help predict the prognosis of patients with stage III serous ovarian cancer as well as suggest targets for the development of new treatment regimens.

Expression of FOXP1 in epithelial ovarian cancer (EOC) and its correlation with chemotherapy resistance and prognosis

“…For example, in breast cancer, Rayoo's research indicated that patients with a high expression of FOXP1 protein have a good prognosis [19]; yet, Giatromanolaki et al have shown that in low-risk, early-stage endometrial cancers, there was no correlation between FOXP1 and overall survival. Kim et al reported that FOXP1 mRNA decreases in stage III serous ovarian carcinoma; yet, the prognosis of patients with chemoresistance was predicted to be very poor when genes such as RNses K, FOXP1, and LAMB2 were upregulated [12]. The present study is the first to analyze a large sample of chemotherapy-resistant tissues from follow-up patients, and our findings indicate that the downregulation of FOXP1 protein expression is associated with chemotherapy resistance and poor prognosis of ovarian cancer patients.…”

“…The results showed that FOXP1 mRNA levels decreased significantly with an increase in the malignancy grade. However, Kim et al found that FOXP1 mRNA was upregulated in chemoresistant ovarian tissues [12]. Therefore, further studies are needed to clarify this issue.…”

Upregulation and Clinicopathological Significance of Long Non-coding NEAT1 RNA in NSCLC Tissues

“…This lncRNA has been recently revealed to be an architectural component of a subnuclear structure called the paraspeckle, which is suggested to be involved in regulating gene expression by retaining mRNAs for editing in the nucleus (Chen and Carmichael, 2009). Anomalous NEAT1 expression has been reported in human malignancies, including of leukemia and ovarian carcinoma (Kim et al, 2010;Zeng et al, 2014). However, it is not yet fully understood how NEAT1 affects carcinogenesis and biological behavior of NSCLC.…”

BRCA1-mediated signaling pathways in ovarian carcinogenesis

“…5 (legend) for other information tumor suppressor as well as an oncogene depending on the type of cancer and is potentially valued as a therapeutic target (Koon et al 2007). In the case of serous ovarian cancer, overexpression of FOXP1 is associated with poor prognosis and chemo-resistance (Kim et al 2010). Another member of the FOX transcription factor family, FOXA2 or forkhead box protein A2, was found to be downregulated in a comparative gene expression profiling of the chemo-resistant and chemo-sensitive ovarian tumors (Ju et al 2009).…”