Role of stratifin (14-3-3 sigma) in adenocarcinoma of gallbladder: A novel prognostic biomarker

Sirivatanauksorn, Vorapan; Dumronggittigule, Wethit; Dulnee, Benjamaporn; Srisawat, Chatchawan; Sirivatanauksorn, Yongyut; Pongpaibul, Ananya; Masaratana, Patarabutr; Somboonyosdech, Chayapol; Sripinitchai, Sirinapa; Kositamongkol, Prawat; Mahawithitwong, Prawej; Tovikkai, Chutwichai; Sangserestid, Pholasith; Limsrichamrern, Somchai

doi:10.1016/j.suronc.2019.10.022

Cited by 14 publications

(12 citation statements)

References 20 publications

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“…Over-expression of SFN has been reported in human malignant tumors. SFN is also a prognostic factor for many malignant tumors, such as ovarian cancer [14], gliomas [13] and gallbladder cancer [31]. As expected, SFN was up-regulated in HCC patients and associated with aggressive clinicopathological features.…”

Section: Discussionsupporting

confidence: 67%

Stratifin Indicates Worse Prognosis and Promotes Hepatocellular Carcinoma Proliferation, Migration, Invasion and EMT By Modulating Wnt/β-Catenin Pathway

Cheng¹,

Li²,

Shi³

et al. 2021

Preprint

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Background: Stratifin (SFN) is closely related to the tumor progression. However, the role of SFN in hepatocellular carcinoma (HCC) is still unknown. The purpose of this study is to investigate the clinical value, biological role and regulatory mechanisms of SFN in HCC. Methods: Immunohistochemistry and RT-qPCR was used to explore SFN expression in HCC tissues and corresponding adjacent non-tumor tissues. The SFN expression profile data and clinical data of HCC patients were extracted from GEO, TCGA and Oncomine database. The univariate and multivariate analysis were used to investigate the prognosis value of the SFN gene in patients with HCC based on online database. The effects of SFN on HCC cell proliferation, migration, invasion was investigated by preforming CCK-8, colony formation, wound healing and Transwell assays. Xenograft nude mouse were used to observe the role of SFN on tumor growth. Western blotting was used to explore the genes associated with Epithelial mesenchymal transformation (EMT) and Wnt/β-catenin signaling. The luciferase reported assay was used to validate the activity of Wnt signal pathway.Results: In this study, we found SFN was upregulated in HCC cell lines and tissues. Clinically, SFN was positively associated with tumor size, degree of differentiation, TNM stage and vascular invasion. Survival analysis indicated that patients with high SFN levels had worse OS and DFS. SFN was an independent prognostic factor for HCC. Biologically, knockdown of SFN repressed tumor cell proliferation, migration, invasion, epithelial-to-mesenchymal transition (EMT) in vitro and tumor growth in vivo. Conversely, overexpression of SFN promoted these effects. Moreover, SFN promoted matrix metalloproteinases-2 (MMP-2) and MMP-9 expression. Mechanistically, SFN activated Wnt/β-catenin pathway by promoting GSK-3β phosphorylation, decreasing β-catenin phosphorylation, promoting β-catenin nuclear translocation, increasing c-Myc expression and inhibiting Axin2 expression. Furthermore, the TOP/FOP-Flash reporter assays indicated that SFN overexpression or SFN knockdown obviously up-regulated or down-regulated Wnt signaling activity. Conclusions: SFN indicates worse survival in HCC and promotes HCC growth, migration, invasion and EMT by activating Wnt/β-catenin pathway. Our results suggest SFN may become a prognostic factor and therapeutic target for patients with HCC in future.

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Section: Discussionsupporting

confidence: 67%

Stratifin Indicates Worse Prognosis and Promotes Hepatocellular Carcinoma Proliferation, Migration, Invasion and EMT By Modulating Wnt/β-Catenin Pathway

Cheng¹,

Li²,

Shi³

et al. 2021

Preprint

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“…An elevated PI3K/AKT signalling is considered a hallmark of cancer and contributes to the initiation and progression of the disease by promoting cell survival and increasing the ability to migrate and metastasize other tissues [ 2 , 20 , 29 , 58 , 59 , 60 ]. Due to its central role in cancer, different molecular players of the PI3K/AKT pathway were already reported as potential genetic-based biomarkers or targets for cancer treatment [ 28 , 59 , 61 , 62 , 63 ]. Still, to the best of our knowledge, there are no reports on PI3K/AKT signalling epigenetic-based biomarkers although these present several advantages when compared to genetic or protein-based biomarkers [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

DNA Methylation of PI3K/AKT Pathway-Related Genes Predicts Outcome in Patients with Pancreatic Cancer: A Comprehensive Bioinformatics-Based Study

Faleiro

Roberto

Canli

et al. 2021

Cancers

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Pancreatic cancer (PCA) is one of the most lethal malignancies worldwide with a 5-year survival rate of 9%. Despite the advances in the field, the need for an earlier detection and effective therapies is paramount. PCA high heterogeneity suggests that epigenetic alterations play a key role in tumour development. However, only few epigenetic biomarkers or therapeutic targets have been identified so far. Here we explored the potential of distinct DNA methylation signatures as biomarkers for early detection and prognosis of PCA. PI3K/AKT-related genes differentially expressed in PCA were identified using the Pancreatic Expression Database (n = 153). Methylation data from PCA patients was obtained from The Cancer Genome Atlas (n = 183), crossed with clinical data to evaluate the biomarker potential of the epigenetic signatures identified and validated in independent cohorts. The majority of selected genes presented higher expression and hypomethylation in tumour tissue. The methylation signatures of specific genes in the PI3K/AKT pathway could distinguish normal from malignant tissue at initial disease stages with AUC > 0.8, revealing their potential as PCA diagnostic tools. ITGA4, SFN, ITGA2, and PIK3R1 methylation levels could be independent prognostic indicators of patients’ survival. Methylation status of SFN and PIK3R1 were also associated with disease recurrence. Our study reveals that the methylation levels of PIK3/AKT genes involved in PCA could be used to diagnose and predict patients’ clinical outcome with high sensitivity and specificity. These results provide new evidence of the potential of epigenetic alterations as biomarkers for disease screening and management and highlight possible therapeutic targets.

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“…It is also interesting to mention that stratifin (SNF), a highly conserved ubiquitously expressed protein, is associated with many different cellular processes and directly linked to cancer onset and progression. [ 50 , 51 ]. In our analysis, both PATJ and SNF were upregulated in the urine of ccRCC patients stratified as advanced stage and early grade ( Table 4 and Table S3 ).…”

Section: Discussionmentioning

confidence: 99%

Does the Urinary Proteome Reflect ccRCC Stage and Grade Progression?

et al. 2021

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Due its ability to provide a global snapshot of kidney physiology, urine has emerged as a highly promising, non-invasive source in the search for new molecular indicators of disease diagnosis, prognosis, and surveillance. In particular, proteomics represents an ideal strategy for the identification of urinary protein markers; thus, a urinomic approach could also represent a powerful tool in the investigation of the most common kidney cancer, which is clear cell Renal Cell Carcinoma (ccRCC). Currently, these tumors are classified after surgical removal using the TNM and nuclear grading systems and prognosis is usually predicted based upon staging. However, the aggressiveness and clinical outcomes of ccRCC remain heterogeneous within each stratified group, highlighting the need for novel molecular indicators that can predict the progression of these tumors. In our study, we explored the association between the urinary proteome and the ccRCC staging and grading classification. The urine proteome of 44 ccRCC patients with lesions of varying severity was analyzed via label-free proteomics. MS data revealed several proteins with altered abundance according to clinicopathological stratification. Specifically, we determined a panel of dysregulated proteins strictly related to stage and grade, suggesting the potential utility of MS-based urinomics as a complementary tool in the staging process of ccRCC.

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Role of stratifin (14-3-3 sigma) in adenocarcinoma of gallbladder: A novel prognostic biomarker

Cited by 14 publications

References 20 publications

Stratifin Indicates Worse Prognosis and Promotes Hepatocellular Carcinoma Proliferation, Migration, Invasion and EMT By Modulating Wnt/β-Catenin Pathway

Stratifin Indicates Worse Prognosis and Promotes Hepatocellular Carcinoma Proliferation, Migration, Invasion and EMT By Modulating Wnt/β-Catenin Pathway

DNA Methylation of PI3K/AKT Pathway-Related Genes Predicts Outcome in Patients with Pancreatic Cancer: A Comprehensive Bioinformatics-Based Study

Does the Urinary Proteome Reflect ccRCC Stage and Grade Progression?

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