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Abstract
Taxol is a widely used chemotherapy drug used clinically for ovarian cancer, although the response to Taxol among individuals varies due to the heterogeneity among ovarian cancer patients. In this work, we analyzed differences in the prognostic effect of gene expression and Taxol usage in the Cancer Genome Atlas (TCGA) dataset and identified specific genes associated with the Taxol effect. Using the Cox regression model, a risk model (Taxol score) was developed to assess the outcome of ovarian cancer patients who underwent chemotherapy with Taxol. According to the results, survival was significantly associated with the Taxol score. Moreover, the patients in the high and low Taxol score group had different responses to Taxol. This result was further validated in another two independent datasets. The correlation between clinicopathological indicators was also analyzed, and we determined that the Taxol score is not associated with age, pathological stage, or Taxol treatment, while there was significant correlation with tumor size and grade. Gene Set Enrichment Analysis (GSEA) showed that various signaling pathways including ECM receptor, drug metabolism and ascorbate metabolism pathways were significantly enriched in the high Taxol score group. Collectively, these results indicate that the model is robust for predicting the effectiveness of Taxol by reflecting the various cell statuses of serous ovarian carcinoma.
Highlights
Ovarian carcinoma is one of the most common causes of cancer related death[1]
Genes significantly associated with survival in the the Cancer Genome Atlas (TCGA)-Taxol receiving group (p0.05) were identified, that smeleeacntesdalalsccoamndbiidnaatteiognesnferso.mAlSl tn1hCe nicowmasbtinesatteidon(swohfetrheencraenfderids atotetgheenceasnwdeidreate genes and C indicates the combination, and i is from 1-n), and we developed a risk model using Cox multivariate regression with each combination using the following formula and each combination, Taxol score 1⁄4 Pni cixi where ci is the coefficient resolved and xi is the relative gene expression level
The expression levels of candidate genes that were not significantly associated with survival (p>0.05) in the Taxol-depleted group were determined using Cox univariate regression to exclude to probability that the gene is a prognostic gene for ovarian cancer but not involved in Taxol resistance
Summary
Ovarian carcinoma is one of the most common causes of cancer related death[1]. It was estimated that there were 52,100 new cases and 22,500 deaths in 2015 according to a recent cancer statistic in China [2]. Among the subtypes of ovarian cancer, serous ovarian carcinoma comprises the majority of the cases. Since radiation is not suitable for serous ovarian carcinoma therapy and targeted drugs have not been widely used, chemotherapy is currently the major treatment method for serous ovarian carcinoma after surgery. Due to the heterogeneity of ovarian serous carcinoma, Taxol resistance was detected in a large proportion of patients. This allowed for biomarkers and genes associated with Taxol resistance to be identified.
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