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.


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.
Department of clinical laboratory, Affiliated to Medical College of Southeast University and Xuzhou Central Hospital, Xuzhou, People's Republic of China. Electronic address: niuguoping_js@sina.com.
Guoping
G
Niu
Department of clinical laboratory, Affiliated to Medical College of Southeast University and Xuzhou Central Hospital, Xuzhou, People's Republic of China.
Duping
D
Wang
Department of clinical laboratory, Affiliated to Medical College of Southeast University and Xuzhou Central Hospital, Xuzhou, People's Republic of China.
Yunfeng
Y
Pei
Department of clinical laboratory, Affiliated to Medical College of Southeast University and Xuzhou Central Hospital, Xuzhou, People's Republic of China.
Li
L
Sun
D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D053574:Receptors, Interleukin-1 Type II / Q000235:genetics / Q000378:metabolism; D051818:Replication Protein C / Q000235:genetics / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; C508592:IL1R2 protein, human; C497563:RFC4 protein, human; D053574:Receptors, Interleukin-1 Type II; D051818:Replication Protein C
Bioinformatics; CDKN2A; Cervical cancer; IL1R2; RFC4