Cartilage Oligomeric Matrix Protein: A Potential Prognostic Biomarker and Therapeutic Target in Gastric Cancer.

IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Dongbing Li, Guizhen Lyu
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引用次数: 0

Abstract

Background: Cartilage oligomeric matrix protein (COMP) is a protein that has been implicated in the development of some tumors, but its exact role in gastric cancer (GC) remains unclear.

Objective: The study aims to comprehensively examine COMP in GC and to confirm its effects through experimental methods.

Methods: The research harnessed data from the Cancer Genome Atlas (TCGA) to explore the significance of COMP in GC and its potential as a diagnostic tool. The study also examined the regulatory networks involving COMP, including its interactions with immune cells, immune checkpoint genes, tumor mutational burden (TMB), microsatellite instability (MSI), and the stemness index based on mRNA expression (mRNAsi). Additionally, the study explored the relationship between COMP expression and drug sensitivity in GC. Genomic variations of COMP in GC were assessed. The expression of COMP was validated by the GEPIA2 tool and confirmed with quantitative reverse transcription PCR (qRT-PCR) in cell lines (normal human gastric epithelial cells GES-1 and GC cell lines AGS and HGC-27).

Results: Abnormal expression patterns of COMP were observed in various cancers, including GC. Higher levels of COMP in GC were significantly associated with the pathologic T stage and a history of reflux (p < 0.05 for both). Elevated COMP expression was correlated with poorer progression-free survival (PFS) (p = 0.027). COMP expression levels were identified as an independent prognostic factor for GC (p = 0.017). COMP was linked to TCF-dependent signaling in response to ECM receptor interaction, focal adhesion, and other pathways. There was an association between COMP expression and immune infiltration, immune checkpoint genes, TMB/MSI, and mRNAsi in GC. COMP expression was inversely correlated with the sensitivity to several drugs, indicating that higher levels of COMP may reduce the effectiveness of these drugs. COMP was found to be significantly up-regulated in GC cell lines.

Conclusions: COMP could serve as a prognostic biomarker and a potential therapeutic target for the treatment of GC.

软骨寡聚基质蛋白:胃癌的潜在预后生物标志物和治疗靶点。
背景:软骨寡聚基质蛋白(COMP)是一种与某些肿瘤的发生有关的蛋白,但其在胃癌(GC)中的确切作用尚不清楚。目的:全面考察气相色谱中COMP的作用,并通过实验方法证实其作用。方法:利用癌症基因组图谱(TCGA)的数据,探讨COMP在胃癌中的意义及其作为诊断工具的潜力。该研究还研究了涉及COMP的调控网络,包括其与免疫细胞、免疫检查点基因、肿瘤突变负担(TMB)、微卫星不稳定性(MSI)和基于mRNA表达的干性指数(mRNAsi)的相互作用。此外,本研究还探讨了GC中COMP表达与药物敏感性的关系。评估GC中COMP的基因组变异。通过GEPIA2工具验证COMP的表达,并通过定量反转录PCR (qRT-PCR)在细胞系(正常人胃上皮细胞GES-1和胃癌细胞系AGS和HGC-27)中进行证实。结果:COMP在包括胃癌在内的多种肿瘤中均有异常表达。GC中较高水平的COMP与病理T分期和反流史显著相关(p < 0.05)。COMP表达升高与较差的无进展生存期(PFS)相关(p = 0.027)。COMP表达水平被确定为胃癌的独立预后因素(p = 0.017)。在ECM受体相互作用、局灶黏附和其他途径中,COMP与tcf依赖性信号有关。GC中COMP表达与免疫浸润、免疫检查点基因、TMB/MSI和mRNAsi相关。COMP的表达与几种药物的敏感性呈负相关,表明较高的COMP水平可能降低这些药物的有效性。COMP在GC细胞系中显著上调。结论:COMP可作为胃癌的预后生物标志物和潜在的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Current medicinal chemistry
Current medicinal chemistry 医学-生化与分子生物学
CiteScore
8.60
自引率
2.40%
发文量
468
审稿时长
3 months
期刊介绍: Aims & Scope Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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