Overexpression of FZD7 is associated with poor survival in patients with colon cancer

Ye, Chengwei; Xu, Meifang; Lin, Min; Zhang, Yiyi; Zheng, Xin; Sun, Yanwu; Deng, Yu; Pan, Jie; Xu, Zongbin; Lu, Xingrong; Chi, Pan

doi:10.1016/j.prp.2019.152478

Cited by 10 publications

(9 citation statements)

References 18 publications

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“…Through bioinformatics prediction and dual luciferase reporter assays, FZD8 was verified the miR‐375‐3p target gene in BC cells. The members of the FZD receptor family, which include FZD2, 53 FZD3, 54 FZD4, 55 FZD7, 56 and FZD10, 57 have been revealed to be involved in many types of cancers. Among them, FZD8 is a classical receptor of Wnt with multiple functions; it can activate canonical or noncanonical Wnt/β‐catenin pathways and plays a pro‐inflammatory role in chronic bronchitis, 58 is involved in brain development and size 59 ; and enhances cell‐cycle dynamics in the developing neocortex 60 .…”

Section: Discussionmentioning

confidence: 99%

The role of exosomal miR‐375‐3p: A potential suppressor in bladder cancer via the Wnt/β‐catenin pathway

Huyan

Cai

et al. 2020

FASEB j.

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miR‐375‐3p is a significantly downregulated miRNA in bladder cancer (BC). However, its role in BC regulation is still unclear. In this study, we reported that miR‐375‐3p overexpression inhibited proliferation and migration and promoted apoptosis in BC cells. Frizzled‐8 (FZD8) gene is identified as the direct miR‐375‐3p targeting gene. miR‐375‐3p blocks the Wnt/β‐catenin pathway and downstream molecules Cyclin D1 and c‐Myc by inhibiting the expression of FZD8 directly, it could increase caspase 1 and caspase 3 expression and promote T24 cell apoptosis as well. miR‐375‐3p also showed a significant inhibitory effect in vivo in bladder tumor‐bearing nude mice, as demonstrated by the reduced tumor volume and Ki67 proliferation index in tumor tissue. Collectively, miR‐375‐3p is a suppressor of BC that inhibits proliferation and metastasis, and promotes apoptosis in BC cells as well as suppresses tumor growth in a T24 xenograft mouse model, which could be used as a potential therapeutic approach for BC in future.

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Section: Discussionmentioning

confidence: 99%

The role of exosomal miR‐375‐3p: A potential suppressor in bladder cancer via the Wnt/β‐catenin pathway

Huyan

Cai

et al. 2020

FASEB j.

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“…High levels of Wnt5a and its receptor Ror2 have been associated with drug resistance in CRC by concomitant induction of non-canonical Wnt signaling and suppression of canonical Wnt signaling (Bordonaro et al, 2011). Apart from these Wnt ligands, various Fz receptors including Fz4, Fz7, and Fz10, are also upregulated in CRC and their elevated levels have been associated with increased stemness, metastasis and recurrence (Cancer Genome Atlas Network, 2012;Ye et al, 2019;Chi et al, 2020). Wnt co-receptor Lrp6 is likewise significantly upregulated in many tumoral tissues of CRC in correlation with high malignancy and poor prognosis (Rismani et al, 2017).…”

Section: Colorectal Cancermentioning

confidence: 99%

Regulation of Wnt Signaling Pathways at the Plasma Membrane and Their Misregulation in Cancer

Azbazdar

Karabicici

Erdal

et al. 2021

Front. Cell Dev. Biol.

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Wnt signaling is one of the key signaling pathways that govern numerous physiological activities such as growth, differentiation and migration during development and homeostasis. As pathway misregulation has been extensively linked to pathological processes including malignant tumors, a thorough understanding of pathway regulation is essential for development of effective therapeutic approaches. A prominent feature of cancer cells is that they significantly differ from healthy cells with respect to their plasma membrane composition and lipid organization. Here, we review the key role of membrane composition and lipid order in activation of Wnt signaling pathway by tightly regulating formation and interactions of the Wnt-receptor complex. We also discuss in detail how plasma membrane components, in particular the ligands, (co)receptors and extracellular or membrane-bound modulators, of Wnt pathways are affected in lung, colorectal, liver and breast cancers that have been associated with abnormal activation of Wnt signaling. Wnt-receptor complex components and their modulators are frequently misexpressed in these cancers and this appears to correlate with metastasis and cancer progression. Thus, composition and organization of the plasma membrane can be exploited to develop new anticancer drugs that are targeted in a highly specific manner to the Wnt-receptor complex, rendering a more effective therapeutic outcome possible.

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“…C-index, also known as concordance" statistic or C-statistic, is a measure of goodness of fit for survival outcomes in a CPH model, and higher C-index means higher predictive ability [21]. Therefore, to further confirm the performance of our multigene panel, we compared the C-indexes, calculated by using the R package "survcomp [22]" , with a total of 10 biomarkers reported by others [23][24][25][26][27][28][29][30][31][32][33]. Student T test was used to compare C-indexes between two groups.…”

Section: Comparison Of the Prognostication Performance Of Our Multigementioning

confidence: 99%

“…As mentioned above, we compared the performance of our multigene panel with 10 existing biomarkers (including a 4-gene signature [23], a 15-gene signature [24], two 6-gene signatures [25,28], a 10-gene signature [26], a 5-gene signature [27], AEBP1 [29], FZD7 [30], CDX2 [31], MUC2 [31], PPM1H [32], and LAYN [33]). As shown in figure 6, the C-index of our multigene panel was significantly higher or comparable with the existing biomarkers in the training set, test set, TCGA-COAD, and GSE17536, indicating that our multigene panel had comparable prognostication performance.…”

Section: The Prognostic Performance Of Our Multigene Panel Was Comparmentioning

confidence: 99%

Multigene panel predicting survival of patients with colon cancer

Liang

2019

J. Cancer

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Objective: The purpose of this study was to investigate multigene panel markers to predict long-term survival in patients with colon cancer. Methods and materials: GSE39582 was randomly divided into a training set and a validation set, while TCGA-COAD and GSE17536 were treated as two independent validation cohorts. Survival-associated genes were included in elastic net penalized Cox proportional hazards regression (ENCPH) model. Based on the results of the ENCPH, a multigene panel was constructed. We evaluated predictive performance of the multigene panel by univariate and multivariate survival analysis, and time-dependent ROC analysis. Results: A total of 1025 colon cancer patients were included in the study, and 94 genes were showed to be related with the overall survival of colon cancer patients, of which 7 genes were integrated to construct a multigene panel according to ENCPH model. The multigene panel could stratify colon cancer patients into notably different risk groups in the training set and three verification cohort. Results of multivariable CPH model suggested that the multigene panel was an independent prognostication factor. The multigene-containing nomogram showed reliable prediction ability on the 3-and 5-year survival of colon cancer patients with internally and externally validated C-indexes exceeded 0.7. Conclusion: The multigene panel we introduced showed considerable prognosis performance in colon cancer, and the multigene panel containing nomogram would help clinicians assess long-term survival probability.

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Overexpression of FZD7 is associated with poor survival in patients with colon cancer

Cited by 10 publications

References 18 publications

The role of exosomal miR‐375‐3p: A potential suppressor in bladder cancer via the Wnt/β‐catenin pathway

The role of exosomal miR‐375‐3p: A potential suppressor in bladder cancer via the Wnt/β‐catenin pathway

Regulation of Wnt Signaling Pathways at the Plasma Membrane and Their Misregulation in Cancer

Multigene panel predicting survival of patients with colon cancer

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