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多巴胺及多巴胺受体D1作为肝细胞癌一种新的有利生物标志物。

Dopamine and dopamine receptor D1 as a novel favourable biomarker for hepatocellular carcinoma.

作者信息

Wang Zhihui, Wen Peihao, Hu Bowen, Cao Shengli, Shi Xiaoyi, Guo Wenzhi, Zhang Shuijun

机构信息

Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Zhengzhou, 450052, Henan, China.

Zhengzhou Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou, 450052, China.

出版信息

Cancer Cell Int. 2021 Oct 30;21(1):586. doi: 10.1186/s12935-021-02298-9.

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) remains one of the most common malignant tumours worldwide. Therefore, the identification and development of sensitivity- genes as novel diagnostic markers and effective therapeutic targets is urgently needed. Dopamine and dopamine receptor D1 (DRD1) are reported to be involved in the progression of various cancers. However, the crucial role of DRD1 in HCC malignant activities remains unclear.

METHODS

We enrolled 371 patients with liver hepatocellular carcinoma (LIHC) from The Cancer Genome Atlas (TCGA) to detect the expression and functions of DRD1. The Tumour Immune Estimation Resource (TIMER), UALCAN database, Kaplan-Meier plotter, cBioPortal database, and LinkedOmics database were utilized for the systematic investigation of DRD1 expression and related clinical features, coexpressed genes, functional pathways, mutations, and immune infiltrates in HCC.

RESULTS

In this study, we determined that DRD1 expression was decreased in HCC tumour tissues versus normal tissues and that low DRD1 expression indicated a poor prognosis. The significance of DRD1 expression varied among different tumour samples. The somatic mutation frequency of DRD1 in the LIHC cohort was 0.3%. The biological functions of DRD1 were detected and validated, and DRD1 was shown to be involved in various functional activities, including metabolism, oxidation, mitochondrial matrix-related processes and other related signaling pathways. In addition, out study indicated that DRD1 had significant correlations with the infiltration of macrophages, B cells and CD+ T cells in HCC.

CONCLUSIONS

These findings demonstrated the rationality of the potential application of DRD1 function as a novel biomarker for HCC diagnosis and a therapeutic target for HCC treatment.

摘要

背景

肝细胞癌(HCC)仍是全球最常见的恶性肿瘤之一。因此,迫切需要鉴定和开发敏感性基因作为新型诊断标志物和有效的治疗靶点。据报道,多巴胺和多巴胺受体D1(DRD1)参与多种癌症的进展。然而,DRD1在HCC恶性活动中的关键作用仍不清楚。

方法

我们从癌症基因组图谱(TCGA)中纳入了371例肝细胞肝癌(LIHC)患者,以检测DRD1的表达和功能。利用肿瘤免疫评估资源(TIMER)、UALCAN数据库、Kaplan-Meier绘图仪、cBioPortal数据库和LinkedOmics数据库,对HCC中DRD1的表达及相关临床特征、共表达基因、功能通路、突变和免疫浸润进行系统研究。

结果

在本研究中,我们确定HCC肿瘤组织中DRD1的表达低于正常组织,且DRD1低表达提示预后不良。DRD1表达的意义在不同肿瘤样本中有所不同。LIHC队列中DRD1的体细胞突变频率为0.3%。检测并验证了DRD1的生物学功能,结果显示DRD1参与多种功能活动,包括代谢、氧化、线粒体基质相关过程及其他相关信号通路。此外,我们的研究表明,DRD1与HCC中巨噬细胞、B细胞和CD+T细胞的浸润显著相关。

结论

这些发现证明了将DRD1功能作为HCC诊断的新型生物标志物和HCC治疗靶点进行潜在应用的合理性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18fe/8557590/af6ff148ca55/12935_2021_2298_Fig1_HTML.jpg

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