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解整合素金属蛋白酶(ADAMs)的泛癌分析:一种用于预后以及化疗和免疫治疗反应的有前景的生物标志物。

Pan-cancer analysis of ADAMs: A promising biomarker for prognosis and response to chemotherapy and immunotherapy.

作者信息

Ma Bo, Yu Riyue

机构信息

Department of Stomatology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.

出版信息

Front Genet. 2023 Apr 4;14:1105900. doi: 10.3389/fgene.2023.1105900. eCollection 2023.

Abstract

Members of a disintegrin and metalloproteinase (ADAM) family play a vital role in cancer development. However, a comprehensive analysis of the landscape of the ADAM family in pan-cancer remains to be performed. The correlation of the expression level and prognostic value with ADAMs in a pan-cancer cohort and the relationship between ADAMs and the stemness score, tumour microenvironment (TME), chemotherapy-related drug sensitivity, immune subtype, and immunotherapy outcome were investigated. ADAMs were differentially expressed between tumour and para-carcinoma tissues in the pan-cancer cohort, and the expression of ADAMs was significantly correlated with patient prognosis. Furthermore, ADAMs were significantly correlated with the stromal score and immune score based on the TME analysis. Additionally, ADAMs were also correlated with DNAss and RNAss in the pan-cancer cohort. On investigating the CellMiner database, ADAMs were revealed to be significantly correlated with the sensitivity of various drugs, including raloxifene and tamoxifen. Moreover, in the IMvigor210 and GSE78220 cohorts, ADAMs were correlated with immunotherapy response and immune activation genes. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were utilised to determine the differential level of ADAM9 in cancer and para-carcinoma tissues in patients' samples. This study elucidates the importance of ADAMs in cancer progression and lays a foundation for further exploration of ADAMs as potential pan-cancer targets.

摘要

解整合素金属蛋白酶(ADAM)家族成员在癌症发展中起着至关重要的作用。然而,对泛癌中ADAM家族全貌的综合分析仍有待进行。本研究调查了泛癌队列中ADAMs的表达水平与预后价值的相关性,以及ADAMs与干性评分、肿瘤微环境(TME)、化疗相关药物敏感性、免疫亚型和免疫治疗结果之间的关系。在泛癌队列中,肿瘤组织和癌旁组织之间ADAMs存在差异表达,且ADAMs的表达与患者预后显著相关。此外,基于TME分析,ADAMs与基质评分和免疫评分显著相关。另外,在泛癌队列中,ADAMs也与DNAss和RNAss相关。通过研究CellMiner数据库发现,ADAMs与多种药物的敏感性显著相关,包括雷洛昔芬和他莫昔芬。此外,在IMvigor210和GSE78220队列中,ADAMs与免疫治疗反应和免疫激活基因相关。此外,利用定量实时聚合酶链反应(qRT-PCR)和免疫组织化学(IHC)来确定患者样本中癌组织和癌旁组织中ADAM9的差异水平。本研究阐明了ADAMs在癌症进展中的重要性,并为进一步探索ADAMs作为潜在的泛癌靶点奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7097/10110990/761a910ab2b8/fgene-14-1105900-g001.jpg

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