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黏附调节分子 1(ADRM1)可以作为膀胱癌的一个潜在的生物标志物和治疗靶点。

Adhesion-regulating molecule 1 (ADRM1) can be a potential biomarker and target for bladder cancer.

机构信息

Department of Pathology, Taizhou Hospital, Wenzhou Medical University, Linhai, 317000, Zhejiang Province, China.

Ningbo Clinical Pathology Diagnosis Center, Ningbo City, Zhejiang Province, China.

出版信息

Sci Rep. 2023 Sep 8;13(1):14803. doi: 10.1038/s41598-023-41992-8.

DOI:10.1038/s41598-023-41992-8
PMID:37684377
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10491834/
Abstract

Adhesion-regulating molecule 1 (ADRM1) has been implicated in tumor development, yet its specific role in bladder cancer (BC) remains undefined. This study aimed to elucidate the function of ADRM1 in BC through a combination of bioinformatics analysis and immunohistochemical analysis (IHC). Utilizing R version 3.6.3 and relevant packages, we analyzed online database data. Validation was conducted through IHC data, approved by the Institutional Ethics Committee (Approval No. K20220830). In both paired and unpaired comparisons, ADRM1 expression was significantly elevated in BC tissues compared to adjacent tissues, as evidenced by the results of TCGA dataset and IHC data. Patients with high ADRM1 expression had statistically worse overall survival than those with low ADRM1 expression in TCGA dataset, GSE32548 dataset, GSE32894 dataset, and IHC data. Functional analysis unveiled enrichment in immune-related pathways, and a robust positive correlation emerged between ADRM1 expression and pivotal immune checkpoints, including CD274, PDCD1, and PDCD1LG2. In tumor microenvironment, samples with the high ADRM1 expression contained statistical higher proportion of CD8 + T cells and Macrophage infiltration. Meanwhile, these high ADRM1-expressing samples displayed elevated tumor mutation burden scores and stemness indices, implying potential benefits from immunotherapy. Patients with low ADRM1 expression were sensitive to cisplatin, docetaxel, vinblastine, mitomycin C, and methotrexate. According to the findings from bioinformatics and IHC analyses, ADRM1 demonstrates prognostic significance for BC patients and holds predictive potential for both immunotherapy and chemotherapy responses. This underscores its role as a biomarker and therapeutic target in BC.

摘要

黏附调节分子 1(ADRM1)已被牵涉到肿瘤的发展中,但它在膀胱癌(BC)中的具体作用仍未确定。本研究旨在通过生物信息学分析和免疫组织化学分析(IHC)的组合来阐明 ADRM1 在 BC 中的作用。使用 R 版本 3.6.3 和相关的软件包,我们分析了在线数据库数据。通过机构伦理委员会批准的 IHC 数据进行了验证(批准号:K20220830)。在配对和非配对比较中,TCGA 数据集和 IHC 数据的结果均表明,ADRM1 在 BC 组织中的表达明显高于相邻组织。在 TCGA 数据集、GSE32548 数据集、GSE32894 数据集和 IHC 数据中,ADRM1 高表达的患者总生存明显比 ADRM1 低表达的患者差。功能分析揭示了免疫相关途径的富集,ADRM1 表达与关键免疫检查点之间存在稳健的正相关,包括 CD274、PDCD1 和 PDCD1LG2。在肿瘤微环境中,ADRM1 高表达的样本中 CD8+T 细胞和巨噬细胞浸润的比例更高。同时,这些高 ADRM1 表达的样本显示出更高的肿瘤突变负担评分和干性指数,表明免疫治疗可能有益。ADRM1 低表达的患者对顺铂、多西他赛、长春碱、丝裂霉素 C 和甲氨蝶呤敏感。根据生物信息学和 IHC 分析的结果,ADRM1 对 BC 患者的预后具有重要意义,并对免疫治疗和化疗反应具有预测潜力。这凸显了它在 BC 中作为生物标志物和治疗靶标的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1af6/10491834/6a047fbfad2e/41598_2023_41992_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1af6/10491834/a64cdcaaadb2/41598_2023_41992_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1af6/10491834/6a047fbfad2e/41598_2023_41992_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1af6/10491834/a64cdcaaadb2/41598_2023_41992_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1af6/10491834/31c73168d85a/41598_2023_41992_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1af6/10491834/ff998c1d1d0a/41598_2023_41992_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1af6/10491834/ea40c402f4f5/41598_2023_41992_Fig4_HTML.jpg
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