DNASE1L3 as a Novel Diagnostic and Prognostic Biomarker for Lung Adenocarcinoma Based on Data Mining.

Jianlin Chen,Yifan Sun,Guowen Qiu,Yangyang Liu,Junping Ding,Xiaoling He,Zhenni Lu,Gan Gao,Peiying Long,Jinping Chen,Lishu Wei,Qianmei Zhan,Lin Sun,Wenjie Huang

doi:10.3389/fgene.2021.699242

Abstract

Previous researches have highlighted that low-expressing deoxyribonuclease1-like 3 (DNASE1L3) may play a role as a potential prognostic biomarker in several cancers. However, the diagnosis and prognosis roles of DNASE1L3 gene in lung adenocarcinoma (LUAD) remain largely unknown. This research aimed to explore the diagnosis value, prognostic value, and potential oncogenic roles of DNASE1L3 in LUAD. We performed bioinformatics analysis on LUAD datasets downloaded from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus), and jointly analyzed with various online databases. We found that both the mRNA and protein levels of DNASE1L3 in patients with LUAD were noticeably lower than that in normal tissues. Low DNASE1L3 expression was significantly associated with higher pathological stages, T stages, and poor prognosis in LUAD cohorts. Multivariate analysis revealed that DNASE1L3 was an independent factor affecting overall survival (HR = 0.680, p = 0.027). Moreover, decreased DNASE1L3 showed strong diagnostic efficiency for LUAD. Results indicated that the mRNA level of DNASE1L3 was positively correlated with the infiltration of various immune cells, immune checkpoints in LUAD, especially with some m6A methylation regulators. In addition, enrichment function analysis revealed that the co-expressed genes may participate in the process of intercellular signal transduction and transmission. GSEA indicated that DNASE1L3 was positively related to G protein-coupled receptor ligand biding (NES = 1.738; P adjust = 0.044; FDR = 0.033) and G alpha (i) signaling events (NES = 1.635; P adjust = 0.044; FDR = 0.033). Our results demonstrated that decreased DNASE1L3 may serve as a novel diagnostic and prognostic biomarker associating with immune infiltrates in lung adenocarcinoma.

Highlights

Lung cancer is the leading cause of cancer-related mortality worldwide
Deng et al (Deng et al, 2021) investigated the expression levels of DNASE1L3, and the results revealed the DNASE1L3 was a prognostic biomarker in cancer of the breast, kidney, liver, stomach, lung adenocarcinoma, and sarcoma via bioinformatics analysis using TCGA database
Our results demonstrated that both the mRNA and protein levels of DNASE1L3 were noticeably downregulated in lung adenocarcinoma (LUAD) compared with normal tissues

Summary

Introduction

Lung cancer is the leading cause of cancer-related mortality worldwide. Lung adenocarcinoma (LUAD), known as pulmonary adenocarcinoma, accounts for 60% of all lung cancers (Denisenko et al, 2018). Activation of protooncogenes is known to play vital role in the formation of the vast majority of cancers, and gaining insight into its expression levels and disease-related prognosis may contribute to the development of effective diagnosis and prevention of lung adenocarcinoma. It has been proved that DNASE1L3 plays vital role in DNA catabolism and cell apoptosis (Errami et al, 2012; Han et al, 2020). Study has reported that DNASE1L3 was involved in breast cancer signal transduction (Sjoblom et al, 2006). Malecki et al found that hyper expressive of DNASE1L3 gene can degrade the genome of ovarian cancer cells and lead to cell death (Malecki et al, 2013). The role of DNASE1L3 in LUAD has not been well elucidated, which is the aim of our study

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