Integrated analysis of single-cell RNA-seq and bulk RNA-seq reveals MMP mediated expression patterns by distinct tumor microenvironment immune profiles in cervical cancer.

IF 3.3 3区 医学 Q2 ONCOLOGY Journal of Cancer Pub Date : 2024-08-13 eCollection Date: 2024-01-01 DOI:10.7150/jca.96429
He Wang, Xinbo Li, Siyu Zhou, Wendi Guo, Zhao Wang, Linlin Sun, Zhongyi Zhao, Yanyan Han, Sanyuan Zhang, Jieping Lv, Yi Ping, Zhe Wang
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Abstract

Background: Few studies have analyzed the effect of matrix metalloproteinase (MMP) expression patterns on the tumor microenvironment (TME) during development of cervical cancer (CC). Methods: We elucidated the landscape and score of MMP expression in CC using single-cell RNA sequencing (scRNA-seq) and RNA sequencing datasets. Further, we aimed the MMPscore to probe the infiltration of immune cells. Further, MMP expression was measured by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Results: We found MMPs were cell-type specific expressed in diverse types of CC cells, regulating the relative pathways of CC progression. Two distinct MMP expression patterns that associated infiltrated tumor microenvironment (TME) were identified. We discovered MMP expression patterns can predict the stage of tumor, subtype, stromal activity in the TME, genetic variation, and patient outcome. Patients with high MMPscore benefited from significantly better treatment and clinical outcomes. Conclusion: These results indicate high MMPscore in diverse cell types may regulate immune response and improve the survival of patients with CC, which assist in developing more effective immunization strategies.

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单细胞 RNA-seq 和大量 RNA-seq 的综合分析揭示了宫颈癌中不同肿瘤微环境免疫图谱介导的 MMP 表达模式。
背景:很少有研究分析基质金属蛋白酶(MMP)表达模式对宫颈癌(CC)发病过程中肿瘤微环境(TME)的影响。研究方法我们利用单细胞RNA测序(scRNA-seq)和RNA测序数据集阐明了MMP在宫颈癌中的表达格局和得分。此外,我们还利用 MMPscore 来探测免疫细胞的浸润情况。此外,我们还通过实时聚合酶链式反应(qRT-PCR)对 MMP 的表达进行了定量检测。结果显示我们发现MMPs在不同类型的CC细胞中表达具有细胞类型特异性,调节着CC进展的相对途径。我们发现两种不同的 MMP 表达模式与肿瘤微环境(TME)浸润有关。我们发现,MMP表达模式可以预测肿瘤的分期、亚型、TME中的基质活性、基因变异和患者预后。MMP评分高的患者治疗效果和临床预后明显更好。结论这些结果表明,不同细胞类型中的高MMPscore可调节免疫反应,提高CC患者的生存率,有助于制定更有效的免疫策略。
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来源期刊
Journal of Cancer
Journal of Cancer ONCOLOGY-
CiteScore
8.10
自引率
2.60%
发文量
333
审稿时长
12 weeks
期刊介绍: Journal of Cancer is an open access, peer-reviewed journal with broad scope covering all areas of cancer research, especially novel concepts, new methods, new regimens, new therapeutic agents, and alternative approaches for early detection and intervention of cancer. The Journal is supported by an international editorial board consisting of a distinguished team of cancer researchers. Journal of Cancer aims at rapid publication of high quality results in cancer research while maintaining rigorous peer-review process.
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