Molecular gene signature and prognosis of non-small cell lung cancer

Huang, Poyin; Cheng, Chu-Yun; Chang, Yun‐chien; Liu, Chia-Hsin; Hsu, Yi Chiung; Chen, Jin‐Shing; Chang, Gee Chen; Ho, Bing-Ching; Su, Kang-Yi; Chen, Hsuan Yu; Yu, Sung-Liang

doi:10.18632/oncotarget.10622

Cited by 20 publications

(15 citation statements)

References 49 publications

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“…These interplays may lead to tumor initiation, progression, metastasis, and relapse . UHRF1 is reported as a tumor epigenetic modulator toward malignancy in lung cancer and as a diagnostic biomarker . Our results are in agreement with this line of evidence, since its inferred activity was upregulated in the two‐tailed GSEA analysis and associated with poor prognosis in survival analyses.…”

Section: Discussionsupporting

confidence: 91%

Integrated transcriptomics reveals master regulators of lung adenocarcinoma and novel repositioning of drug candidates

Bastiani

Klamt

2019

Cancer Medicine

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Background Lung adenocarcinoma is the major cause of cancer‐related deaths in the world. Given this, the importance of research on its pathophysiology and therapy remains a key health issue. To assist in this endeavor, recent oncology studies are adopting Systems Biology approaches and bioinformatics to analyze and understand omics data, bringing new insights about this disease and its treatment. Methods We used reverse engineering of transcriptomic data to reconstruct nontumorous lung reference networks, focusing on transcription factors (TFs) and their inferred target genes, referred as regulatory units or regulons. Afterwards, we used 13 case‐control studies to identify TFs acting as master regulators of the disease and their regulatory units. Furthermore, the inferred activation patterns of regulons were used to evaluate patient survival and search drug candidates for repositioning. Results The regulatory units under the influence of ATOH8, DACH1, EPAS1, ETV5, FOXA2, FOXM1, HOXA4, SMAD6, and UHRF1 transcription factors were consistently associated with the pathological phenotype, suggesting that they may be master regulators of lung adenocarcinoma. We also observed that the inferred activity of FOXA2, FOXM1, and UHRF1 was significantly associated with risk of death in patients. Finally, we obtained deptropine, promazine, valproic acid, azacyclonol, methotrexate, and ChemBridge ID compound 5109870 as potential candidates to revert the molecular profile leading to decreased survival. Conclusion Using an integrated transcriptomics approach, we identified master regulator candidates involved with the development and prognostic of lung adenocarcinoma, as well as potential drugs for repurposing.

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Section: Discussionsupporting

confidence: 91%

Integrated transcriptomics reveals master regulators of lung adenocarcinoma and novel repositioning of drug candidates

Bastiani

Klamt

2019

Cancer Medicine

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“…As enhanced expression significantly correlated with the advanced stages and malignancy of the cancer, authors proposed UHRF1 as a prognostic biomarker for lung cancer [ 87 ]. Similarly, a recent study in Taiwan has predicted a six-gene signature including ABCC4 , ADRBK2 , KLHL23 , PDS5A , UHRF1 and ZNF551 as better prognostic marker in NSCLC for overall survival time and treatment outcome [ 88 ].…”

Section: Uhrf1 Expression In Different Cancersmentioning

confidence: 99%

The epigenetic integrator UHRF1: on the road to become a universal biomarker for cancer

et al. 2017

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Cancer is one of the deadliest diseases in the world causing record number of mortalities in both developed and undeveloped countries. Despite a lot of advances and breakthroughs in the field of oncology still, it is very hard to diagnose and treat the cancers at early stages. Here in this review we analyze the potential of Ubiquitin-like containing PHD and Ring Finger domain 1 (UHRF1) as a universal biomarker for cancers. UHRF1 is an important epigenetic regulator maintaining DNA methylation and histone code in the cell. It is highly expressed in a variety of cancers and is a well-known oncogene that can disrupt the epigenetic code and override the senescence machinery. Many studies have validated UHRF1 as a powerful diagnostic and prognostic tool to differentially diagnose cancer, predict the therapeutic response and assess the risk of tumor progression and recurrence. Highly sensitive, non-invasive and cost effective approaches are therefore needed to assess the level of UHRF1 in patients, which can be deployed in diagnostic laboratories to detect cancer and monitor disease progression.

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“…In addition, the expression of UHRF1 changes through the cell cycle; it peaks during late G1 and G2/M stages in normal cells and remains at a high level in tumour cells ( 18 ). Indeed, the expression of UHRF1 is markedly upregulated in multiple types of cancer, such as lung, liver and breast cancer ( 19 – 21 ). Overexpressed UHRF1 plays a crucial role in epigenetic changes (DNA methylation and histone modification), and several tumour suppressor genes (including p16INK4A, BRCA1, RB1, CDH13, SHP1, SOCS3 and CDX2) were reported to be related to UHRF1 epigenetic silencing, which allows cancer cells to escape apoptosis and promote tumour progression ( 22 ).…”

Section: Discussionmentioning

confidence: 99%

Upregulation of UHRF1 promotes the progression of melanoma by inducing cell proliferation

Wei

Wang

et al. 2018

Oncol Rep

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Melanoma is the most aggressive cutaneous cancer due to its propensity to metastasise and proliferate. Melanoma accounts for 80–90% of skin-cancer related deaths worldwide. Alhough numerous published studies have attempted to define the markers of diagnosis and prognosis of melanoma, a sensitive and specific biomarker for melanoma remains unknown. Recently, ubiquitin-like with PHD and ring finger domains 1 (UHRF1) has attracted attention due to its role in cell proliferation and it has been deemed as a potential therapeutic target for cancer. The aim of the present study was to investigate the role and the clinical significance of UHRF1 in melanoma. Immunohistochemical analysis was performed with tissue microarray (TMA) to examine the expression of UHRF1 and Ki-67, and the role of UHRF1 in cell proliferation was determined through CCK-8, colony formation and flow cytometry by interfering with the expression of UHRF1. Subsequently, the relationship among the expression of UHRF1 and several major clinical characteristics of melanoma were analysed to evaluate the role of UHRF1 in the progression of melanoma. Finally, the clinical significance of UHRF1 was estimated in 56 melanoma patients. It was observed that the expression of UHRF1 was significantly upregulated in melanoma compared with benign nevi tissues (P<0.05). In addition, the downregulation of the expression of UHRF1 significantly decreased cell proliferation. Furthermore, the level of UHRF1 was positively correlated with the expression of Ki-67 in melanoma cells, as well as in melanoma tissues. Clinically, a high level of UHRF1 was prone to be related to a high TNM classification (P=0.017) and Breslow's thickness (P=0.034) of melanoma. Furthermore, a high level of UHRF1 was positively associated with a shorter overall survival of melanoma patients. Importantly, the Cox regression model analysis demonstrated that the expression of UHRF1 was an independent prognostic factor for the overall survival of melanoma patients. In conclusion, the elevated expression of UHRF1 plays an important role in melanoma cell proliferation and progression, and it can be used as a prognostic biomarker for melanoma.

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Molecular gene signature and prognosis of non-small cell lung cancer

Cited by 20 publications

References 49 publications

Integrated transcriptomics reveals master regulators of lung adenocarcinoma and novel repositioning of drug candidates

Integrated transcriptomics reveals master regulators of lung adenocarcinoma and novel repositioning of drug candidates

The epigenetic integrator UHRF1: on the road to become a universal biomarker for cancer

Upregulation of UHRF1 promotes the progression of melanoma by inducing cell proliferation

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