Identification of key genes in response to radiotherapy and chemotherapy in esophageal squamous cell carcinoma based on multiple datasets
10.3760/cma.j.cn113030-20231025-00141
- VernacularTitle:食管鳞状细胞癌放化疗敏感性关键基因的鉴定
- Author:
Yaowen ZHANG
1
;
Yunsong LIU
;
Zhouguang HUI
;
Shasha CAO
;
Chenyu WANG
;
Xinyu CHENG
;
Linzhi JIN
;
Runchuan REN
Author Information
1. 安阳市肿瘤医院放疗科，河南科技大学附属安阳市肿瘤医院，河南省食管癌精准防治医学重点实验室，安阳 455000
- Keywords:
Esophageal squamous cell carcinoma;
Chemoradiotherapy;
Weighted gene co-expression network analysis;
HUB gene;
Competing endogenous RNA network
- From:
Chinese Journal of Radiation Oncology
2024;33(10):950-957
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the biomarkers of radiochemotherapy sensitivity and potential mechanisms in esophageal squamous cell carcinoma (ESCC), and validate the screened biomarkers at human tissue, animal and cellular levels.Methods:Based on bioinformatics system, clinical and transcriptome data of ESCC were obtained from The Cancer Genome Atlas (TCGA) and GEO databases. HUB genes related to chemoradiotherapy sensitivity were identified by weighted correlation network analysis (WGCNA) and cytoscape software and survival differences were analyzed. CellMiner database was used to predict and screen drugs with strong correlation with HUB genes. The expression levels of HUB genes in clinical tissues was detected by real-time reverse transcription PCR (qRT-PCR). Then, oe-AKR1C1 mouse model, cisplatin-resistant cells and radiation-resistant cells were constructed, and the effects of HUB genes on tumor size and mass, and cell proliferation ability were analyzed.Results:A total of 5 HUB genes were identified, among which NAD(P)H quinone dehydrogenase 1 (NQO1), AKR1C1 and NADH: ubiquinone oxidoreductase core subunit S2 (NDUFS2) were significantly correlated with ESCC survival (all P<0.05). Dacarbazine, alectinib and obatoclax were the anti-tumor drugs predicted to have a strong correlation with HUB genes in this study. Human tissue test results showed that the expression levels of NQO1, AKR1C1 and NDUFS2 were up-regulated in patients with chemoradiotherapy resistance, and AKR1C1 and NDUFS2 had statistical significance (both P<0.05). The results of mouse tumor bearing experiment showed that the tumor volume and mass of oe-AKR1C1 mice after radiotherapy and chemotherapy were significantly higher than those in the control group (both P<0.05). The cell experiment results showed that the expression levels of AKR1C1 and NDUFS2 in radiation-resistant cells and cisplatin-resistant cells were significantly higher than those in control cells ( P<0.05), while there was no statistically significant difference in the relative expression level of NQO1. Conclusion:NQO1, AKR1C1 and NDUFS2 are HUB genes significantly related to the survival of ESCC, which can be used as important therapeutic tumor targets for ESCC.
