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DNASE1L3作为一种与癌症免疫细胞浸润相关的预后生物标志物。

DNASE1L3 as a Prognostic Biomarker Associated with Immune Cell Infiltration in Cancer.

作者信息

Deng Zenghua, Xiao Mengmeng, Du Dexiao, Luo Nan, Liu Dongfang, Liu Tingting, Lian Dongbo, Peng Jirun

机构信息

Ninth School of Clinical Medicine, Peking University, Beijing, 100038, People's Republic of China.

Department of Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People's Republic of China.

出版信息

Onco Targets Ther. 2021 Mar 18;14:2003-2017. doi: 10.2147/OTT.S294332. eCollection 2021.

DOI:10.2147/OTT.S294332
PMID:33776450
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7987320/
Abstract

OBJECTIVES

Deoxyribonuclease 1 like 3 (DNASE1L3) is critically involved in apoptosis and immune response, however, its role in cancer has yet to be deciphered. We aimed to explore the prognostic value of DNASE1L3 across a series of malignancies.

METHODS

Based on Oncomine database and Tumor Immune Estimation Resource (TIMER), expression profiling of DNASE1L3 was detailed in malignancies. Using PrognoScan, Kaplan-Meier Plotter, GEPIA2, and bc-GenEcMiner v4.5, prognostic value of DNASE1L3 was estimated in diverse cancers. Based on TIMER, association between DNASEL13 expression and immune infiltration was examined in various cancers. Then, mRNA level of DNASE1L3 in hepatocellular carcinoma (HCC) samples (n=22) and stomach adenocarcinoma (STAD) samples (n=17) was measured with qRT-PCR. Immunohistochemistry was performed to confirm expression of DNASE1L3 in paraffin-embedded tissues of HCC (n=9) and lung adenocarcinoma (n=20).

RESULTS

DNASE1L3 was downregulated in multiple cancers, including breast invasive carcinoma (BRCA), cholangiocarcinoma (CHOL), liver hepatocellular carcinoma (LIHC), and lung adenocarcinoma (LUAD). A lower level of DNASE1L3 correlated with poorer prognosis in various cancers, especially in breast, liver, kidney, stomach, lung adenocarcinoma and sarcoma (SARC). Moreover, DNASE1L3 was positively related to immune cell infiltration in many cancers, including BRCA, LIHC, STAD, LUAD, and SARC. DNASE1L3 was significantly associated with CCR7/CCL19 in cancers. DNASE1L3 was downregulated in HCC and STAD tissues as demonstrated by qRT-PCR, as well as in HCC and LUAD samples, as shown by immunohistochemistry.

CONCLUSION

DNASE1L3 has potential to serve as a prognostic biomarker in cancer of the breast, kidney, liver, stomach, lung adenocarcinoma and sarcoma. Down-regulation of DNASE1L3 may participate in immune escape via CCR7/CCL19 axis.

摘要

目的

脱氧核糖核酸酶1样3(DNASE1L3)在细胞凋亡和免疫反应中起关键作用,然而,其在癌症中的作用尚未明确。我们旨在探讨DNASE1L3在一系列恶性肿瘤中的预后价值。

方法

基于Oncomine数据库和肿瘤免疫评估资源(TIMER),详细分析了DNASE1L3在恶性肿瘤中的表达谱。使用PrognoScan、Kaplan-Meier Plotter、GEPIA2和bc-GenEcMiner v4.5评估DNASE1L3在多种癌症中的预后价值。基于TIMER,研究了DNASEL13表达与多种癌症中免疫浸润的相关性。然后,采用qRT-PCR检测肝细胞癌(HCC)样本(n=22)和胃腺癌(STAD)样本(n=17)中DNASE1L3的mRNA水平。进行免疫组织化学以确认DNASE1L3在HCC(n=9)和肺腺癌(n=20)石蜡包埋组织中的表达。

结果

DNASE1L3在多种癌症中下调,包括乳腺浸润性癌(BRCA)、胆管癌(CHOL)、肝细胞癌(LIHC)和肺腺癌(LUAD)。DNASE1L3水平较低与多种癌症的预后较差相关,尤其是在乳腺癌、肝癌、肾癌胃腺癌、肺腺癌和肉瘤(SARC)中。此外,DNASE1L3在许多癌症中与免疫细胞浸润呈正相关,包括BRCA、LIHC、STAD、LUAD和SARC。在癌症中,DNASE1L3与CCR7/CCL19显著相关。qRT-PCR结果显示,DNASE1L3在HCC和STAD组织中下调,免疫组织化学结果显示,在HCC和LUAD样本中也下调。

结论

DNASE1L3有可能作为乳腺癌、肾癌、肝癌、胃癌、肺腺癌和肉瘤的预后生物标志物。DNASE1L3的下调可能通过CCR7/CCL19轴参与免疫逃逸。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe93/7987320/5a60438b2be7/OTT-14-2003-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe93/7987320/af87b2281ffe/OTT-14-2003-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe93/7987320/cb2db80f523a/OTT-14-2003-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe93/7987320/8052515de6b1/OTT-14-2003-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe93/7987320/4bd757037e3b/OTT-14-2003-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe93/7987320/79584fc133c4/OTT-14-2003-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe93/7987320/55a3116f8e96/OTT-14-2003-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe93/7987320/5a60438b2be7/OTT-14-2003-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe93/7987320/af87b2281ffe/OTT-14-2003-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe93/7987320/cb2db80f523a/OTT-14-2003-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe93/7987320/8052515de6b1/OTT-14-2003-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe93/7987320/4bd757037e3b/OTT-14-2003-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe93/7987320/79584fc133c4/OTT-14-2003-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe93/7987320/55a3116f8e96/OTT-14-2003-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe93/7987320/5a60438b2be7/OTT-14-2003-g0007.jpg

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