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Gene expression-profiling to predict induction chemotherapy efficacy in locoregionally advanced nasopharyngeal carcinoma

ABSTRACT: Gene expression-profiling to predict induction chemotherapy efficacy in locoregionally advanced nasopharyngeal carcinoma

PROVIDER: PRJNA545965 | ENA |

REPOSITORIES: ENA

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Project description:This study aimed to develop a novel gene expression signature that can predict tumor response to induction chemotherapy (IC) before treatment. RNA sequencing (RNA-seq) was used to screen the differentially expressed genes (DEGs) between response and non-response in 54 samples (discovery cohort). Random forest (RF) and receiver operating characteristic (ROC) analyses were performed to further screen principal genes using the RNA-seq data of 27 cases (training cohort). qRT-PCR was used to confirm the relative expression of the selected genes between 57 non-response tissues and 55 response tissues (validation cohort). K-means was used to stratify all patients into two clusters according to the 6-gene signature. Kaplan-Meier analysis was used to estimate overall survival in the two clusters. The log-rank survival test was performed to compare the differences between the two clusters. In the discovery phase, 107 DEGs were obtained. It effectively distinguished tumors from normal tissues and distinguished response tumors from non-response tumors by RNA sequencing. In the training phase, the top 50 genes were selected by RF, which showed distinct transcriptome segregation between response and non-response tumors. Then, the performance of the 50 genes was evaluated to predict the tumor response of IC using ROC analysis. Among them, 10 genes were chosen for which the area under the curve was more than 80%. In the validation phase, six genes (CD72, NRIP1, THBS4, ABCA9, SNED1, and GIMAP7) were significantly overexpressed in non-response tissues compared to response tissues (p < 0.05). Finally, the 6-gene signature was developed, which was highly accurate in predicting the short-term tumor response to IC (AUC= 0.949) and was also an independent prognostic factor for predicting the overall survival of locoregionally advanced laryngeal and hypopharyngeal carcinoma (LA-LHC) patients. The 6-gene signature can effectively predict tumor response to IC and overall survival, which lays the foundation for a more individualized therapeutic strategy for LA-LHC patients.

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Gene expression-profiling to predict induction chemotherapy efficacy in locoregionally advanced nasopharyngeal carcinoma

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