Aim An in silico pathway analysis was performed in an attempt to identify new biomarkers for cervical carcinoma.
Methods Three 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).
Results Seven 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 reviewed
Conclusion Novel 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
- cervical cancer
- cervical cancer screening
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Statistics from Altmetric.com
Contributors PAvD and SVL designed the study and performed the data acquisition and analysis. Interpretation of the data and drafting and revision of the manuscript was performed by PAvD, CR, CVB, XBT, PP, JPB and SVL.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests PAvD, CR and XBT received travel/expenses/congress grants from Roche.
Patient consent Not required.
Ethics approval The studies generating the gene array data sets (GSE5787, GSE7803, GSE9750, GSE7410) used were conducted in accordance with the ethical standards of the relevant institutional and/or national research committees and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Provenance and peer review Not commissioned; externally peer reviewed.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.