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胃癌的化学敏感性:关键致病转录因子分析

Chemosensitivity of gastric cancer: analysis of key pathogenic transcription factors.

作者信息

Weng Jianze, Wu Aixiang, Ying Jingwen

机构信息

Department of Pharmacy, The Affiliated People's Hospital of Ningbo University, Ningbo, China.

出版信息

J Gastrointest Oncol. 2022 Jun;13(3):977-984. doi: 10.21037/jgo-22-274.

Abstract

BACKGROUND

We aimed to screen the key pathogenic transcription factors of gastric cancer and analyzed the correlation between the expression of transcription factors and chemotherapy drugs in gastric cancer.

METHODS

Gastric cancer RNA sequencing data sets, single nucleotide polymorphism data sets, and corresponding clinical data sets were downloaded from The Cancer Genome Atlas, which is public data. The expression of transcription factors in gastric cancer and normal tissues was analyzed with R software. Pathway enrichment analysis of differentially expressed transcription factors was performed using the Kyoto Encyclopedia of Genes and Genomes database. Univariate Cox analysis was used to explore the correlation between the differential expression of transcription factors and prognosis. The interaction network among differentially expressed transcription factors was constructed using String database. Spearman test was used to explore the correlation between transcription factor mutation and gene expression. The Genomics of Drug Sensitivity in Cancer database was used to examine the relationship between the expression of transcription factors and chemotherapeutic drug sensitivity.

RESULTS

A total of 17 differentially expressed transcription factors were screened. The results indicated that , , , , , and were prognostic risk factors for gastric cancer patients (P<0.05), while and were prognostic protective factors for gastric cancer patients (P<0.05). interacted with , , , , and . gene mutation was positively correlated with the expression level (P<0.05). Based on the median value of , the patients were divided into high expression group and low expression group of . There was no significant difference in IC50 of 5-fluorouracil between the high expression group and the low expression group (P>0.05). The IC50 of paclitaxel in the high expression group was higher than that in the low expression group (P<0.001). The expression of IC50 of cisplatin in the high expression group was higher than that in the low expression group (P<0.05).

CONCLUSIONS

was a highly expressed transcription factor in gastric cancer. High expression was associated with the resistance of gastric cancer patients to paclitaxel and cisplatin. Therefore, is a potential therapeutic target for gastric cancer.

摘要

背景

我们旨在筛选胃癌关键致病转录因子,并分析转录因子表达与胃癌化疗药物之间的相关性。

方法

从癌症基因组图谱(The Cancer Genome Atlas)下载胃癌RNA测序数据集、单核苷酸多态性数据集及相应临床数据集,这些均为公开数据。使用R软件分析胃癌组织和正常组织中转录因子的表达。利用京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes)数据库对差异表达转录因子进行通路富集分析。采用单因素Cox分析探讨转录因子差异表达与预后的相关性。使用String数据库构建差异表达转录因子之间的相互作用网络。采用Spearman检验探讨转录因子突变与基因表达的相关性。利用癌症药物敏感性基因组学(Genomics of Drug Sensitivity in Cancer)数据库研究转录因子表达与化疗药物敏感性之间的关系。

结果

共筛选出17个差异表达转录因子。结果表明,[具体转录因子名称1]、[具体转录因子名称2]、[具体转录因子名称3]、[具体转录因子名称4]、[具体转录因子名称5]、[具体转录因子名称6]是胃癌患者的预后危险因素(P<0.05),而[具体转录因子名称7]和[具体转录因子名称8]是胃癌患者的预后保护因素(P<0.05)。[具体转录因子名称1]与[具体转录因子名称2]、[具体转录因子名称3]、[具体转录因子名称4]、[具体转录因子名称5]、[具体转录因子名称6]相互作用。[具体基因名称]突变与表达水平呈正相关(P<0.05)。根据[具体转录因子名称]的中位数,将患者分为[具体转录因子名称]高表达组和低表达组。[具体转录因子名称]高表达组与低表达组之间5-氟尿嘧啶的IC50无显著差异(P>0.05)。[具体转录因子名称]高表达组中紫杉醇的IC50高于低表达组(P<0.001)。[具体转录因子名称]高表达组中顺铂的IC50表达高于低表达组(P<0.05)。

结论

[具体转录因子名称]是胃癌中高表达的转录因子。[具体转录因子名称]高表达与胃癌患者对紫杉醇和顺铂的耐药性相关。因此,[具体转录因子名称]是胃癌潜在的治疗靶点。

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