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软骨寡聚基质蛋白(COMP)与结直肠癌的疾病进展、部分免疫检查点分子及 SIGLEC9 相关

英文原题:Cartilage Oligomeric Matrix Protein (COMP) Correlates with Disease Progression, Selected Immune Checkpoint Molecules and SIGLEC9 in Colorectal Cancer.

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Cartilage Oligomeric Matrix Protein (COMP) Correlates with Disease Progression, Selected Immune Checkpoint Molecules and SIGLEC9 in Colorectal Cancer.

PubMed 2026/07/05(内容时间) Int J Mol Sci Q1 · IF 5.6(JCR 2025)

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中文摘要

软骨寡聚基质蛋白(COMP)影响细胞外基质重塑。我们研究了其在结直肠癌(CRC)中的临床、预后和免疫调节意义。通过ELISA对107对CRC和正常组织中的COMP进行定量。表达与临床病理特征、突变谱、微卫星不稳定性(MSI)、TIL(肿瘤浸润淋巴细胞)(TILs)、免疫检查点和多重细胞因子网络相关。对于转录组验证,使用FieldEffectCrc数据集进行基因集富集分析(GSEA),并使用癌症基因组图谱(TCGA)CRC队列进行生存分析。COMP在CRC组织中显著上调(p < 0.001),并与晚期T、N和总体病理分期相关(均p < 0.05,tau分别为0.18、0.21和0.23)。

高COMP表达与免疫浸润受限相关(基质TILs减少,p < 0.05,tau = -0.23),微卫星稳定(MSS)肿瘤中水平高于MSI肿瘤(p < 0.01),并与免疫耗竭标志物(T细胞免疫球蛋白和黏蛋白结构域包含-3(TIM-3)、半乳糖凝集素-9(GAL9)、唾液酸结合Ig样凝集素9(SIGLEC9))呈正相关。转录组数据将高COMP与更差的疾病特异性和无进展生存期以及促肿瘤通路(上皮-间质转化、血管生成、IL-6信号传导)富集相关联。COMP上调定义了CRC中的免疫抑制微环境,尤其是在MSS肿瘤中。它代表了一个重要的预后生物标志物和克服免疫治疗耐药性的潜在治疗靶点。

展开英文摘要原文

Cartilage oligomeric matrix protein (COMP) influences extracellular matrix remodeling.

We investigated its clinical, prognostic, and immunomodulatory significance in colorectal cancer (CRC). COMP was quantified via ELISA in 107 paired CRC and normal tissues. Expression was correlated with clinicopathological features, mutational profiles, microsatellite instability (MSI), tumor-infiltrating lymphocytes (TILs), immune checkpoints, and multiplex cytokine networks. For transcriptomic validation, the FieldEffectCrc dataset was used for Gene Set Enrichment Analysis (GSEA), and The Cancer Genome Atlas (TCGA) CRC cohort for survival analysis. COMP was significantly upregulated in CRC tissues ( p < 0. 001) and correlated with advanced T, N, and overall pathological stages (all p < 0. 05, tau = 0. 18, 0. 21, and 0. 23, respectively).

High COMP expression was linked to restricted immune infiltration (reduced stromal TILs, p < 0. 05, tau = -0. 23), elevated levels in microsatellite stable (MSS) compared to MSI tumors ( p < 0. 01), and correlated positively with immune exhaustion markers (T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), galectin-9 (GAL9), sialic acid-binding Ig-like lectin 9 (SIGLEC9)).

Transcriptomic data linked high COMP to worse disease-specific and progression-free survival, and enrichment in pro-tumorigenic pathways (epithelial-to-mesenchymal transition, angiogenesis, IL-6 signaling). COMP upregulation defines an immunosuppressive microenvironment in CRC, particularly in MSS tumors. It represents an important prognostic biomarker and potential therapeutic target for overcoming immunotherapy resistance.

论文信息

作者
Limanówka P、Kot A、Wagner W、Ochman B、Mielcarska S、Kula A、Dawidowicz M、Hudy D
第一作者单位
Department of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 41-808 Zabrze, Poland.Poland
通讯作者单位
Department of Oncological Surgery, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 41-808 Katowice, Poland.Poland
期刊
International journal of molecular sciences2026 Jul 5
原文标识
PubMed 42450298 · DOI 10.3390/ijms27136032