DNASE1L3 as a Prognostic Biomarker Associated with Immune Cell Infiltration in Cancer
Authors Deng Z, Xiao M, Du D, Luo N, Liu D, Liu T, Lian D, Peng J
Received 2 December 2020
Accepted for publication 19 February 2021
Published 18 March 2021 Volume 2021:14 Pages 2003—2017
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Prof. Dr. Takuya Aoki
Zenghua Deng,1,2,* Mengmeng Xiao,3,4,* Dexiao Du,2 Nan Luo,1,2 Dongfang Liu,2 Tingting Liu,2 Dongbo Lian,1,2 Jirun Peng1,2
1Ninth School of Clinical Medicine, Peking University, Beijing, 100038, People’s Republic of China; 2Department of Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China; 3Peking University International Hospital, Beijing, 102206, People’s Republic of China; 4Eighth School of Clinical Medicine, Peking University, Beijing, 102206, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Jirun Peng Tel +86-10-63926721
Email [email protected]
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.
Keywords: DNASE1L3, CCR7, CCL19, prognosis, immune infiltration, tumor
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