Expression and prognostic impact of FZDs in pancreatic adenocarcinoma

Abstract

Background Despite the high number of researches on pancreatic adenocarcinoma (PAAD) over past decades, little progress had been made due to lack of effective treatment regimens. We aimed to investigate the expression level, mutation, and clinical significance of the Frizzled (FZD) family in PAAD so as to establish a sufficient scientific evidence for clinical decisions and risk management. Methods PAAD samples were extracted from The Cancer Genome Atlas (TCGA). Oncomine, Gene expression profiling interactive analysis (GEPIA), human protein atlas (HPA), Kaplan–Meier Plotter, cBioPortal, LinkedOmics, DAVID database, and R software (× 64 3.6.2) were used to comprehensively analyze the roles of FZDs. p value below to 0.05 was considered as significant difference. Results In total, 179 PAAD tissues and 171 paracancerous tissues were included. The expression levels of FZD1, 2, 6, 7, and 8 were higher in PAAD tissues than those in normal pancreatic tissue. The higher the expression levels of FZD2 and FZD7, the higher the clinical stage. The overall survival (OS) time was significantly different between low FZD3, 4, 5, 6, and 9 expression group and high expression group. Multivariable analysis showed that FZD3 and FZD6 were independent prognostic factors. The recurrence free survival (RFS) time was significantly different between low FZD4 and FZD8 expression group and high expression group. The RFS difference between low FZD6 expression group and high expression group had not reached statistical significance (p = 0.067), which might be due to the small sample size. However, multivariable analysis showed that FZD6 was the only independent factor for RFS. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that FZDs played a critical role in the Wnt signaling pathway, which was further confirmation that FZDs were transmembrane receptors of Wnt signaling pathway. Conclusions Our results strongly indicated a crucial role of the FZD family in PAAD. FZD3 and FZD6 could be potential prognostic and predictive markers, and FZD6 might also function as a potential therapeutic target in PAAD by blocking Wnt/β-catenin pathway.

The Prognostic Value of the Developmental Gene FZD6 in Young Saudi Breast Cancer Patients: A Biomarkers Discovery and Cancer Inducers OncoScreen Approach

“…The Wnt receptor FZD6 has received, as far as we know, nearly no attention to its role in BC except a very few studies ( Vouyovitch et al, 2016 ; Corda et al, 2017 ; Poodineh et al, 2020 ). Remarkably, FZD6 has been reasonably studied in other cancer types such as oral ( Putnová et al, 2021 ), prostate ( Vatansever et al, 2014 ), thyroid ( Deng et al, 2015 ), pancreatic adenocarcinoma ( Li et al, 2021 ), osteosarcoma ( De Sá Rodrigues et al, 2017 ), and leukemia ( Wu et al, 2009 ).…”

“…Among the FZD members that have received very little attention in BC is FZD6, despite its important role in other types of cancer including cervical cancer ( Wang et al, 2021 ), colon ( Vincan and Barker, 2008 ; Xu et al, 2019 ), leukaemia ( Wu et al, 2009 ; Yuan et al, 2019 ; Cassaro et al, 2021 ), hepatocarcinoma ( Bengochea et al, 2008 ), squamous cell sarcoma and adenomas ( Haider et al, 2006 ), oral squamous cell carcinoma ( Putnová et al, 2021 ; Sung et al, 2021 ), neuroblastoma ( Cantilena et al, 2011 ), glioblastoma ( Zhang et al, 2021 ), pancreatic adenocarcinoma ( Yang et al, 2019 ; Li et al, 2021 ), and prostate cancer ( Saramäki et al, 2006 ; Han K. et al, 2018 ). Hence, FZD6 was suggested as a promising therapeutic cancer target ( Han K. et al, 2018 ; Zeng et al, 2018 ; Patel et al, 2019 ).…”

GPCR genes as a predictor of glioma severity and clinical outcome

“…[50][51][52] For example, the expression of FZD2 and FZD7 was upregulated in later-stage tumours in pancreatic adenocarcinoma; and FZE10 was highly expressed in the later stages of tumour progression in colon cancer. 53,54 In particular, FZD7 upregulation in glioma patients was associated with a poor prognosis. 55 In fact, aberrant FZD signalling and complex formation between FZDs and Wnt have been associated with several human cancers.…”

A Computational Framework to Identify Biomarkers for Glioma Recurrence and Potential Drugs Targeting Them

“…FZD8 could activate the β-catenin pathway and play a vital role in cancer invasion and metastasis ( Chen et al, 2020 ). Aberrant expression of FZD8 has been reported in gastric cancer, prostate cancer, renal cell carcinoma, lung cancer, pancreatic adenocarcinoma, and overexpression of FZD8 was considered to promote tumor metastasis ( Li et al, 2017 ; Yang et al, 2017 ; Liu et al, 2019 ; Chen et al, 2020 ; Li et al, 2021 ). In addition, overexpression of FZD8 leaded to chemotherapy resistance in breast cancer patients ( Yin et al, 2013 ).…”