鉴定并验证单核细胞向巨噬细胞分化相关因子作为胃癌预后生物标志物的作用

Identification and validation of monocyte to macrophage differentiation-associated as a prognostic biomarker in gastric cancer.

作者信息

Bai Suyang, Chen Zhaofeng, Ji Rui, Wang Yuping, Zhou Yongning, Guo Qinghong, Qiao Liang

机构信息

The First Clinical Medical College, Lanzhou University, Lanzhou, China.

Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.

出版信息

Front Oncol. 2025 Apr 16;15:1508355. doi: 10.3389/fonc.2025.1508355. eCollection 2025.

Abstract

BACKGROUND

Gastric cancer (GC) has a very poor prognosis as most cases are diagnosed at a late stage, which can be partially attributed to a lack of reliable diagnostic biomarkers. Our study reveals a close correlation between monocyte to macrophage differentiation-associated (MMD) and GC.

METHODS

We analyzed data from The Cancer Genome Atlas (TCGA). A close association between MMD levels and the clinicopathological features of gastric cancer patients was identified using Cox regression analysis and KM plot database analysis. Bioinformatics data were validated by real-time polymerase chain reaction and western blot analysis in GC cells. The impact of MMD on GC was examined using multiple complementary assays, including colony formation assay, CCK-8 assay, cell cycle analysis, apoptosis assessment, wound healing assay, transwell assay, and subcutaneous xenograft tumor formation assay in mice.

RESULTS

High levels of MMD were observed in GC tissues. MMD accelerated cell growth and metastasis, and suppressed apoptosis in GC cells. MMD inhibition significantly suppressed the growth of xenograft tumors in mice. Further studies had revealed that MMD expression was suppressed by miR-200b-3p in GC. Dual luciferase experiment indicated that MMD is a direct target gene of miR-200b-3p. MMD might play an oncogenic role in GC by acting as a direct target of miR-200b-3p.

CONCLUSION

MMD plays an oncogenic role in gastric cancer. It may serve as a potential biomarker for GC diagnosis and a therapeutic target.

摘要

背景

胃癌(GC)的预后很差,因为大多数病例在晚期才被诊断出来,这部分归因于缺乏可靠的诊断生物标志物。我们的研究揭示了单核细胞向巨噬细胞分化相关(MMD)与胃癌之间的密切关联。

方法

我们分析了来自癌症基因组图谱(TCGA)的数据。使用Cox回归分析和KM plot数据库分析确定MMD水平与胃癌患者临床病理特征之间的密切关联。通过实时聚合酶链反应和蛋白质免疫印迹分析在胃癌细胞中验证生物信息学数据。使用多种互补试验,包括集落形成试验、CCK-8试验、细胞周期分析、凋亡评估、伤口愈合试验、Transwell试验以及小鼠皮下异种移植瘤形成试验,研究MMD对胃癌的影响。

结果

在胃癌组织中观察到高水平的MMD。MMD促进胃癌细胞的生长和转移,并抑制其凋亡。抑制MMD可显著抑制小鼠异种移植瘤的生长。进一步研究表明,在胃癌中miR-200b-3p可抑制MMD的表达。双荧光素酶实验表明,MMD是miR-200b-3p的直接靶基因。MMD可能通过作为miR-200b-3p的直接靶标在胃癌中发挥致癌作用。

结论

MMD在胃癌中发挥致癌作用。它可能作为胃癌诊断的潜在生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80f6/12040639/f6b94706d7fb/fonc-15-1508355-g001.jpg

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