Preliminary investigation into construction of sensitivity model of adjuvant radiotherapy in cervical cancer based on gene expression data in vivo / 肿瘤研究与临床

ABSTRACT

Objective To construct a radiosensitivity model based on gene expression in tumor tissues, and to explore the feasibility of using this model to select the patients benefiting from adjuvant radiotherapy in cervical cancer. Methods Patients underwent radical hysterectomy alone or radical hysterectomy plus adjuvant radiotherapy were selected from The Cancer Genome Atlas (TCGA) cervical cancer dataset. Candidate radiosensitive genes were identified through multivariate Cox regression analysis with recurrence free survival (RFS) as end-point events. The sum of regression coefficients and products of expression levels of candidate genes was calculated as radiosensitivity index. Time-dependent receiver operating characteristic (ROC) curve analysis was used to analyze the predictive accuracy of this model for RFS. Kaplan-Meier plot coupled with Log-rank test was used to evaluate difference in RFS between subgroups with different radiosensitivity. Results A total of 155 patients underwent radical hysterectomy was retrieved from the phenotype dataset among which 18 patients was completely treated with planned adjuvant radiotherapy. Expression values of 17156 genes and 480 microRNAs after probes filtration were included into analysis. Twenty-three genes were identified consistent with statistical criterion. Hierarchical cluster analysis revealed 7 subgroups existed across these 23 genes. The MAT2A, PIGY, SUSD1, ZNF341, TMEM85, HIF1AN and CLEC18A genes were finally selected to calculate radiosensitivity index. The median value and range of RI was 0.7258 (-5.501 - 9.046). In subset consist of patients underwent radical hysterectomy alone, adjusted for intravascular tumor thrombus, radiosensitivity index was independent prognostic factor (HR = 1.456, 95％CI 1.192-1.780, P<0.01). Whereas, radiosensitivity index was remained significantly associated with RFS after adjustment for the number of positive nodes in subset comprised of patients underwent radical hysterectomy plus adjuvant radiotherapy (HR = 0.572, 95％ CI 0.328-0.998, P = 0.049). Moreover, radiosensitivity index exhibited more accuracy in prediction for 3 or 5 years RFS compared with clinical prognostic factors N stage and intravascular tumor thrombus. Conclusion The radiosensitivity model based on gene expression data in tumor tissues has potential value to select the cervical cancer patients benefiting from adjuvant radiotherapy.