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用于前列腺腺癌治疗的新型治疗化合物:使用生物信息学方法和 CMap 数据库进行的分析。

Novel therapeutic compounds for prostate adenocarcinoma treatment: An analysis using bioinformatic approaches and the CMap database.

机构信息

Departments of Orthopedics, The First Affiliated Hospital, Guangxi Medical University.

Graduate School of Guangxi Medical University, Nanning, Guangxi, PR China.

出版信息

Medicine (Baltimore). 2020 Dec 18;99(51):e23768. doi: 10.1097/MD.0000000000023768.

Abstract

INTRODUCTION

Prostate adenocarcinoma is the most frequently diagnosed malignancy, particularly for people >70 years old. The main challenge in the treatment of advanced neoplasm is bone metastasis and therapeutic resistance for known oncology drugs. Novel treatment methods to prolong the survival time and improve the life quality of these specific patients are required. The present study attempted to screen potential therapeutic compounds for the tumor through bioinformatics approaches, in order to provide conceptual treatment for this malignant disease.

METHODS

Differentially expressed genes were obtained from the Gene Expression Omnibus database and submitted into the Connectivity Map database for the detection of potentially associated compounds. Target genes were extracted from the search results. Functional annotation and pathway enrichment were performed for the confirmation. Survival analysis was used to measure potential therapeutic effects.

RESULTS

It was revealed that 3 compounds (vanoxerine, tolnaftate, and gabexate) may help to prolong the disease-free survival time from tumor metastasis of patients with the tumor. A total of 6 genes [also-keto reductase family 1 member C3 (AKR1C3), collagen type III α 1 chain (COL3A1), lipoprotein lipase (LPL), glucuronidase, β pseudogene 11 (GUSBP11), apolipoprotein E (APOE), and collagen type I α 1 chain (COL1A1)] were identified to be the potential therapeutic targets for the aforementioned compounds.

CONCLUSION

In the present study, it was speculated that 3 compounds may function as the potential therapeutic drugs of bone metastatic prostate adenocarcinoma; however, further studies verifying vitro and in vivo are necessary.

摘要

简介

前列腺腺癌是最常见的恶性肿瘤,特别是对于 >70 岁的人群。在治疗晚期肿瘤时,主要的挑战是骨转移和对已知肿瘤药物的治疗耐药性。需要寻找新的治疗方法来延长这些特定患者的生存时间并提高生活质量。本研究试图通过生物信息学方法筛选肿瘤的潜在治疗化合物,为这种恶性疾病提供概念性治疗。

方法

从基因表达综合数据库中获取差异表达基因,并将其提交到连接图谱数据库中,以检测潜在相关的化合物。从搜索结果中提取靶基因。进行功能注释和通路富集以进行确认。进行生存分析以衡量潜在的治疗效果。

结果

结果显示,3 种化合物(vanoxerine、tolnaftate 和 gabexate)可能有助于延长肿瘤转移患者的无病生存时间。共有 6 个基因[醛酮还原酶家族 1 成员 C3(AKR1C3)、III 型胶原 α1 链(COL3A1)、脂蛋白脂肪酶(LPL)、葡糖醛酸酶、β 假基因 11(GUSBP11)、载脂蛋白 E(APOE)和 I 型胶原 α1 链(COL1A1)]被鉴定为上述化合物的潜在治疗靶点。

结论

在本研究中,推测 3 种化合物可能作为骨转移前列腺腺癌的潜在治疗药物;然而,还需要进一步的体外和体内研究来验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6dd/7748316/3c8b6ac63528/medi-99-e23768-g001.jpg

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