Analyzing the prognostic value of DKK1 expression in human cancers based on bioinformatics

Wei, Ruqiong; Rodríguez, Raquel Alarcón; Requena, Mar; Tan, Zhiyuan; Gui, Yuchang; Hu, Jincui; Zhu, Tingpei; Huang, Xiaoxiao; Zhu, Yanyan; Xu, Jianwen

doi:10.21037/atm-20-3263

Cited by 14 publications

(11 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results demonstrated that DKK1 mRNA was overexpressed in a wide range of tumors (14 out of 27 types analyzed), such as esophageal, colon, stomach, and uterine corpus endometrial carcinoma, providing diverse research directions about the roles of DKK1 in tumors. Consistent with other bioinformatic analysis, a significant overexpression of DKK1 was revealed in head and neck squamous cell carcinoma (HNSC), pancreatic adenocarcinoma (PAAD), and lung squamous cell carcinoma (LUSC), with DKK1 overexpression being associated with shorter disease-free survival (DFS) (42). These results implied that DKK1 could be an advantageous serologic biomarker indicative of tumorigenesis and poor prognosis.…”

Section: Gene Expression Profiles From the Cancer Genome Atlas (Tcga)supporting

confidence: 81%

Dickkopf-1: A Promising Target for Cancer Immunotherapy

et al. 2021

View full text Add to dashboard Cite

Clinical studies in a range of cancers have detected elevated levels of the Wnt antagonist Dickkopf-1 (DKK1) in the serum or tumors of patients, and this was frequently associated with a poor prognosis. Our analysis of DKK1 gene profile using data from TCGA also proves the high expression of DKK1 in 14 types of cancers. Numerous preclinical studies have demonstrated the cancer-promoting effects of DKK1 in both in vitro cell models and in vivo animal models. Furthermore, DKK1 showed the ability to modulate immune cell activities as well as the immunosuppressive cancer microenvironment. Expression level of DKK1 is positively correlated with infiltrating levels of myeloid-derived suppressor cells (MDSCs) in 20 types of cancers, while negatively associated with CD8+ T cells in 4 of these 20 cancer types. Emerging experimental evidence indicates that DKK1 has been involved in T cell differentiation and induction of cancer evasion of immune surveillance by accumulating MDSCs. Consequently, DKK1 has become a promising target for cancer immunotherapy, and the mechanisms of DKK1 affecting cancers and immune cells have received great attention. This review introduces the rapidly growing body of literature revealing the cancer-promoting and immune regulatory activities of DKK1. In addition, this review also predicts that by understanding the interaction between different domains of DKK1 through computational modeling and functional studies, the underlying functional mechanism of DKK1 could be further elucidated, thus facilitating the development of anti-DKK1 drugs with more promising efficacy in cancer immunotherapy.

show abstract

Section: Gene Expression Profiles From the Cancer Genome Atlas (Tcga)supporting

confidence: 81%

Dickkopf-1: A Promising Target for Cancer Immunotherapy

et al. 2021

View full text Add to dashboard Cite

show abstract

“…However, this is the first study to demonstrate that altered interaction of miR-149-5p- HOXA10 might be implicated in penile carcinogenesis. miR-149-5p has also changed the correlation pattern with DKK1 and SOX2 transcripts, both shown overexpressed in HNSCC [ 47 , 48 ]. The other seven miRNA-mRNA pairs in PeC have been reported here for the first time.…”

Section: Discussionmentioning

confidence: 99%

Disruption of miRNA-mRNA Networks Defines Novel Molecular Signatures for Penile Carcinogenesis

Furuya

Murta

Carrasco

et al. 2021

Cancers

View full text Add to dashboard Cite

Penile cancer (PeC) carcinogenesis is not fully understood, and no biomarkers are reported in clinical practice. We aimed to investigate molecular signatures based on miRNA and mRNA and perform an integrative analysis to identify molecular drivers and pathways for PeC development. Affymetrix miRNA microarray was used to identify differentially expressed miRNAs (DEmiRs) comparing 11 tumoral tissues (TT) paired with non-neoplastic tissues (NNT) with further validation in an independent cohort (n = 13). We also investigated the mRNA expression of 83 genes in the total sample. Experimentally validated targets of DEmiRs, miRNA-mRNA networks, and enriched pathways were evaluated in silico. Eight out of 69 DEmiRs identified by microarray analysis were validated by qRT-PCR (miR-145-5p, miR-432-5p, miR-487b-3p, miR-30a-5p, miR-200a-5p, miR-224-5p, miR-31-3p and miR-31-5p). Furthermore, 37 differentially expressed genes (DEGs) were identified when comparing TT and NNT. We identified four downregulated DEmiRs (miR-30a-5p, miR-432-5p, miR-487b-3p, and miR-145-5p) and six upregulated DEGs (IL1A, MCM2, MMP1, MMP12, SFN and VEGFA) as potential biomarkers in PeC by their capacity of discriminating TT and NNT with accuracy. The integration analysis showed eight dysregulated miRNA-mRNA pairs in penile carcinogenesis. Taken together, our findings contribute to a better understanding of the regulatory roles of miRNAs and altered transcripts levels in penile carcinogenesis.

show abstract

“…The clinical diagnostic and prognostic value of serum levels of DKK1 in human cancers is well documented in the literature 22 , 23 . Up to now, however, little is known about circulating levels of DKK1 in PE.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Maternal Serum Levels and Placental mRNA Levels of Dickkopf-1 in Preeclamptic and Normal Pregnant Women at Delivery

Kasoha

Takács

Fackiner

et al. 2021

Geburtshilfe Frauenheilkd

View full text Add to dashboard Cite

Background Preeclampsia remains a major cause of perinatal and maternal mortality and morbidity worldwide. Wnt/β-catenin signaling is known to be critically involved in placenta development processes. Dickkopf-1 (DKK1) is a key regulator of this transduction pathway. The aim of this study is to compare maternal serum DKK1 levels and placental mRNA levels of DKK1 and β-catenin in preeclamptic and normal pregnant women at delivery. Methods The present study included 30 women with preeclampsia and 30 women with normal pregnancy. Maternal serum DKK1 levels were measured by ELISA. Placental mRNA levels of DKK1 and β-catenin were detected using RT-PCR. Results Decreased maternal serum DKK1 levels were associated with worse maternal and fetal complications including HELLP syndrome, determination of one or more pathological symptom and IUGR diagnosis. No significant difference in maternal serum DKK1 levels was reported between preeclamptic women and women with normal pregnancy. Placental mRNA DKK1 levels were lower in preeclamptic women compared with normal pregnant women. Placental mRNA β-catenin levels showed no significant difference between two groups. Conclusions Our findings reported the aberrant placental mRNA DKK1 levels in patients with preeclampsia. In addition, worse preeclampsia features were associated with decreased maternal serum DKK1 levels. Hence, aberrant Wnt/β-catenin signaling might present a plausible mechanism in preeclampsia pathogenicity. Dysregulated expression of DKK1 at gene level in the placenta but not at protein level in the maternal serum might confirm the notion that preeclampsia is a type of placenta-derived disease.

show abstract

Analyzing the prognostic value of DKK1 expression in human cancers based on bioinformatics

Cited by 14 publications

References 48 publications

Dickkopf-1: A Promising Target for Cancer Immunotherapy

Dickkopf-1: A Promising Target for Cancer Immunotherapy

Disruption of miRNA-mRNA Networks Defines Novel Molecular Signatures for Penile Carcinogenesis

Comparison of Maternal Serum Levels and Placental mRNA Levels of Dickkopf-1 in Preeclamptic and Normal Pregnant Women at Delivery

Contact Info

Product

Resources

About