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

软骨寡聚基质蛋白 微卫星不稳定性 癌症研究 癌症 生物标志物 生物 医学 基因 病理 遗传学 替代医学 骨关节炎 等位基因 微卫星
作者
Dongbing Li,Guizhen Lyu
出处
期刊:Current Medicinal Chemistry [Bentham Science Publishers]
卷期号:32
标识
DOI:10.2174/0109298673360512250329171036
摘要

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

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