Potential new biomarkers for squamous carcinoma of the uterine cervix

Abstract

AimAn in silico pathway analysis was performed in an attempt to identify new biomarkers for cervical carcinoma.MethodsThree publicly available Affymetrix gene expression data sets (GSE5787, GSE7803, GSE9750) were retrieved, vouching for a total 9 cervical cancer cell lines, 39 normal cervical samples, 7 CIN3 samples and 111 cervical cancer samples. An Agilent data set (GSE7410; 5 normal cervical samples, 35 samples from invasive cervical cancer) was selected as a validation set. Predication analysis of microarrays was performed in the Affymetrix sets to identify cervical cancer biomarkers. We compared the lists of differentially expressed genes between normal and CIN3 samples on the one hand (n=1923) and between CIN3 and invasive cancer samples on the other hand (n=628).ResultsSeven probe sets were identified that were significantly overexpressed (at least 2 fold increase expression level, and false discovery rate <5%) in both CIN3 samples respective to normal samples and in cancer samples respective to CIN3 samples. From these, five probes sets could be validated in the Agilent data set (P<0.001) comparing the normal with the invasive cancer samples, corresponding to the genes DTL, HMGB3, KIF2C, NEK2 and RFC4. These genes were additionally overexpressed in cervical cancer cell lines respective to the cancer samples. The literature on these markers was reviewedConclusionNovel biomarkers in combination with primary human papilloma virus (HPV) testing may allow complete cervical screening by objective, non-morphological molecular methods, which may be particularly important in developing countries

Bioinformatics analysis shows that TOP2A functions as a key candidate gene in the progression of cervical cancer

“…Among these, GSE63514 and GSE9750 have been analyzed together (26,27). Other studies have also mined the GSE63514 (28) and GSE9750 (29) datasets; only the GSE7410 dataset had not yet been thoroughly examined previously, to the best of our knowledge. Therefore, the GEO2R online tool was used to perform the analyses of the three datasets to determine any potentially relevant factors.…”

Targeting NEK2 impairs oncogenesis and radioresistance via inhibiting the Wnt1/β-catenin signaling pathway in cervical cancer

“…It has also been documented that NEK2 depeltion impairs cancer cell drug resistance through inhibition of the PP1/AKT/NF-κB signaling pathway in multiple myeloma [17,18]. Notably, a recent study reported that the mRNA expression level of NEK2 is significantly higher in invasive cervical cancer than in normal tissue [19], indicating that NEK2 may serve as a tumor-promoting protein in cervical cancer. Nevertheless, the exact roles and underlying mechanisms of NEK2 in cervical cancer progression and radioresistance has not yet been investigated.…”

RANK-RANKL Signaling in Cancer of the Uterine Cervix: A Review

“…Most mild dysplastic lesions disappear spontaneously, but a significant proportion of the CIN III lesions may progress into invasive CC if left untreated [3]. These precancerous lesions have a likelihood of about 95% to be picked up in by screening programs using cytology and/or HPV testing on cervical smears [4]. They can be effectively eradicated by minimally invasive excision or ablation techniques, truly preventing CC.…”

“…Over the last decades metastatic disease was treated with platinum-based chemotherapy, but there has been little improvement in the efficacy of the systemic treatment [3]. The short-lived responses to chemotherapy seen in patients with advanced cervical cancer indicate that the disease is relatively chemorefractory and up to now most new targeted drugs provided no extra survival benefit [3,4]. The Gynecologic Oncology Group (GOG) 240 phase III trial showed that addition of bevacizumab to the current golden standard (combination of topotecan-paclitaxel or cisplatin-paclitaxel) in this population is associated with a moderate increased overall survival (16.8 months vs. 13.3 months) compared to the same cytostatic combinations without antiangiogenic medication.…”