Gene Expression Changes in Residual Advanced Cervical Cancer after Radiotherapy: Indicators of Poor Prognosis and Radioresistance?
Zhi-chao Fu, Feng-mei Wang, Jian-ming Cai
Department of Radiotherapy, Fu Zhou General Hospital, Fuzhou, Fujian, China (mainland)
Med Sci Monit 2015; 21:1276-1287
Different sensitivity of advanced cervical cancer to irradiation can decrease effectiveness of radiotherapy in some cases. We attempted to identify the differentially expressed genes in residual cervical cancer after radiotherapy that might be associated with poor prognosis and radioresistance.
MATERIAL AND METHODS: Differential genes expression was identified by an oligonucleotide microarray in cervical cancer tissues before radiation and after a 50-Gy dose of radiation. The microarray results were validated by quantitative real-time PCR. CXCL12 was validated by immunohistochemistry in paraffin-embedded cervical cancer tissues before radiotherapy. The relationship between the differentiated gene and prognosis was validated by survival analysis.
RESULTS: Hierarchic cluster analysis identified 238 differentiated genes that exhibited ≥3.0-fold change and p<0.05. We found 111 genes that were in persistent up-regulation and 127 in persistent down-regulation after a 50-Gy dose of radiation when compared with the control group. These genes were involved in processes such as cell growth and death, cell-apoptosis, cell cycle regulation, cell signaling, DNA synthesis and repair, and cell adhesion. High differential expression of CXCL12, CD74, FGF7, COL14A1, PRC1, and RAD54L genes was validated by quantitative PCR before and after radiotherapy. Survival analysis results showed that the high expression of CXCL12 was closely related to poor prognosis.
CONCLUSIONS: The higher expression of CXCL12 might be informative regarding poor prognosis in patients undergoing radical radiotherapy. The differentially expressed genes identified in our study might provide a new method for diagnosis and treatment of radioresistance in cervical cancer.
Keywords: Adult, Carcinoma, Squamous Cell - radiotherapy, Chemokine CXCL12 - genetics, Cluster Analysis, Gene Expression Regulation, Neoplastic, Kaplan-Meier Estimate, Neoplasm Proteins - genetics, Oligonucleotide Array Sequence Analysis, Prognosis, Radiation Tolerance, Radiotherapy Dosage, Real-Time Polymerase Chain Reaction, Uterine Cervical Neoplasms - radiotherapy