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利用组学和患者生存数据对胎盘生长因子抑制剂(PGF)的抗癌靶点-适应症优先级进行综合分析。

Comprehensive Analysis for Anti-Cancer Target-Indication Prioritization of Placental Growth Factor Inhibitor (PGF) by Use of Omics and Patient Survival Data.

作者信息

Kim Nari, Ko Yousun, Shin Youngbin, Park Jisuk, Lee Amy Junghyun, Kim Kyung Won, Pyo Junhee

机构信息

Department of Medical Science, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.

Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.

出版信息

Biology (Basel). 2023 Jul 7;12(7):970. doi: 10.3390/biology12070970.

DOI:10.3390/biology12070970
PMID:37508400
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10376188/
Abstract

The expression of the placental growth factor (PGF) in cancer cells and the tumor microenvironment can contribute to the induction of angiogenesis, supporting cancer cell metabolism by ensuring an adequate blood supply. Angiogenesis is a key component of cancer metabolism as it facilitates the delivery of nutrients and oxygen to rapidly growing tumor cells. PGF is recognized as a novel target for anti-cancer treatment due to its ability to overcome resistance to existing angiogenesis inhibitors and its impact on the tumor microenvironment. We aimed to integrate bioinformatics evidence using various data sources and analytic tools for target-indication identification of the target and prioritize the indication across various cancer types as an initial step of drug development. The data analysis included gene function, molecular pathway, protein interaction, gene expression and mutation across cancer type, survival prognosis and tumor immune infiltration association with . The overall evaluation was conducted given the totality of evidence, to target the gene to treat the cancer where the level was highly expressed in a certain tumor type with poor survival prognosis as well as possibly associated with poor tumor infiltration level. showed a significant impact on overall survival in several cancers through univariate or multivariate survival analysis. The cancers considered as target diseases for inhibitors, due to their potential effects on , are adrenocortical carcinoma, kidney cancers, liver hepatocellular carcinoma, stomach adenocarcinoma, and uveal melanoma.

摘要

癌细胞和肿瘤微环境中胎盘生长因子(PGF)的表达可促进血管生成,通过确保充足的血液供应来支持癌细胞代谢。血管生成是癌症代谢的关键组成部分,因为它有助于将营养物质和氧气输送到快速生长的肿瘤细胞。PGF因其能够克服对现有血管生成抑制剂的耐药性及其对肿瘤微环境的影响,而被认为是抗癌治疗的新靶点。我们旨在整合来自各种数据源和分析工具的生物信息学证据,以确定该靶点的适应症,并对各种癌症类型的适应症进行优先级排序,作为药物开发的第一步。数据分析包括基因功能、分子途径、蛋白质相互作用、跨癌症类型的基因表达和突变、生存预后以及与肿瘤免疫浸润的关联。综合所有证据进行总体评估,以靶向该基因来治疗在特定肿瘤类型中高表达且生存预后差以及可能与肿瘤浸润水平低相关的癌症。通过单变量或多变量生存分析,显示对几种癌症的总生存有显著影响。由于其对PGF的潜在影响,被视为PGF抑制剂靶点疾病的癌症有肾上腺皮质癌、肾癌、肝细胞肝癌、胃腺癌和葡萄膜黑色素瘤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d67e/10376188/b78b9d19a06c/biology-12-00970-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d67e/10376188/28c02c1da20f/biology-12-00970-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d67e/10376188/f8abef11c9c3/biology-12-00970-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d67e/10376188/961fd773527d/biology-12-00970-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d67e/10376188/0651adb9cdf1/biology-12-00970-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d67e/10376188/b78b9d19a06c/biology-12-00970-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d67e/10376188/28c02c1da20f/biology-12-00970-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d67e/10376188/f8abef11c9c3/biology-12-00970-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d67e/10376188/961fd773527d/biology-12-00970-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d67e/10376188/0651adb9cdf1/biology-12-00970-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d67e/10376188/b78b9d19a06c/biology-12-00970-g005.jpg

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