Systematic identification of key genes and pathways in the development of invasive cervical cancer.

BACKGROUND:Cervical cancer progresses through different stages: a long stage of precancerous lesions, then high-grade squamous intraepithelial lesion (HSIL) stage in which precancerous lesions transform into invasive cervical carcinoma, and finally invasive squamous cell carcinomas (SCC) which is difficult to be treated and can be deadly. METHODS AND RESULTS:To identify critical genes for the development and progression of cervical cancer development, we analyzed an online database comprised of normal squamous cervical epithelia samples, HSIL samples and SCC of cervix. Dysregulated genes were identified in both early stage (from normal to HSIL stage) and late stage (from HSIL stage to SCC stage) of cervical cancer. By overlapping these dysregulated genes, we found that three genes, including CDKN2A, IL1R2 and RFC4, were not only changed in HSIL, but also significantly changed in SCC, indicating that their dysregulation may contribute to cervical cancer development. Several altered pathways during tumor progression were also discovered, including those involved in cell proliferation, cell cycle and cell division. CONCLUSIONS:Our findings suggest that dysregulations of CDKN2A, IL1R2 and RFC4 may contribute to cervical cancer progression and they might be potential diagnostic markers and therapeutic drug targets.

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