Dataset Information

Exosome Released FZD10 Increases Ki-67 Expression via Phospho-ERK1/2 in Colorectal and Gastric Cancer.

ABSTRACT: Frizzled (FZD) proteins are primary receptors for Wnt signaling that activates the mitogen-activated protein kinase (MAPK) pathways. Dysfunction of Wnt signals with consequently abnormal activation of MAPK3 pathways was found in colorectal cancer (CRC) and gastric cancer (GC). Upregulation of FZD10 protein, localized in the exosomes isolated from plasma of CRC and GC patients, was associated with a poor prognosis. Herein, the expression levels of circulating FZD10 were found to be strongly correlated to their expression levels in the corresponding tissues in CRC and GC patients. Bioinformatic prediction revealed a link between FZD10 and Ki-67 through MAPK3. In both CRC and GC tissues, pERK1/2 levels were significantly increased at more advanced disease stages, and pERK1/2 and Ki-67 were correlated. Silencing of FZD10 in CRC and GC cells resulted in a significant reduction of pERK1/2 and Ki-67 expression, while subsequent treatment with exogenous exosomes partially restored their expression levels. The strong correlation between the expression of Ki-67 in tissues and of FZD10 in exosomes suggests that the exosome-delivered FZD10 may be a promising novel prognostic and diagnostic biomarker for CRC and GC.

SUBMITTER: Scavo MP

PROVIDER: S-EPMC8522497 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Exosome Released FZD10 Increases Ki-67 Expression <i>via</i> Phospho-ERK1/2 in Colorectal and Gastric Cancer.

Scavo Maria Principia MP Rizzi Federica F Depalo Nicoletta N Armentano Raffaele R Coletta Sergio S Serino Grazia G Fanizza Elisabetta E Pesole Pasqua Letizia PL Cervellera Alessandra A Carella Nicola N Curri Maria Lucia ML Giannelli Gianluigi G

Frontiers in oncology 20210923

Frizzled (FZD) proteins are primary receptors for Wnt signaling that activates the mitogen-activated protein kinase (MAPK) pathways. Dysfunction of Wnt signals with consequently abnormal activation of MAPK3 pathways was found in colorectal cancer (CRC) and gastric cancer (GC). Upregulation of FZD10 protein, localized in the exosomes isolated from plasma of CRC and GC patients, was associated with a poor prognosis. Herein, the expression levels of circulating FZD10 were found to be strongly corre ...[more]

PMID: 34671555

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Project description:PurposeTo retrospectively assess whether magnetic resonance (MR) imaging and MR spectroscopic imaging and selected molecular markers correlate with each other and with clinically insignificant and significant prostate cancer (PCa), as defined at surgical pathologic analysis.Materials and methodsThe institutional review board approved this HIPAA-compliant study and waived informed consent. Eighty-nine men (mean age, 63 years; range, 46-79 years) with biopsy-proved PCa underwent combined endorectal MR imaging and MR spectroscopic imaging before radical prostatectomy. Suspicion of clinically insignificant PCa was retrospectively and separately recorded for MR imaging and combined MR imaging and MR spectroscopic imaging by using a scale of 0-3. Clinically insignificant PCa was pathologically defined as organ-confined cancer of 0.5 cm(3) or less without poorly differentiated elements. Prostatectomy specimens underwent immunohistochemical analysis for three molecular markers: Ki-67, phospho-Akt (pAkt), and androgen receptor (AR). To examine differences in marker levels for clinically insignificant and significant cancer, a Wilcoxon rank sum test was used. To examine correlations between marker levels and MR imaging or combined MR imaging and MR spectroscopic imaging scores, the Spearman correlation was used.ResultsTwenty-one (24%) patients had clinically insignificant and 68 (76%) had clinically significant PCa at surgical pathologic review. All markers were significantly correlated with MR imaging and combined MR imaging and MR spectroscopic imaging findings (all correlation coefficients >0.5). In differentiating clinically insignificant from clinically significant PCa, areas under the receiver operating characteristic curves for Ki-67, AR, pAkt, MR imaging, and combined MR imaging and MR spectroscopic imaging were 0.75, 0.78, 0.80, 0.85, and 0.91, respectively.ConclusionThe use of pretreatment MR imaging or combined MR imaging and MR spectroscopic imaging and molecular marker analyses of biopsy samples could facilitate better treatment selection.Supplemental materialhttp://radiology.rsnajnls.org/cgi/content/full/250/3/803/DC1.

Project description:BACKGROUND:The significance of human epidermal growth factor receptor 2 (Her2) and nucleus-associated antigen Ki-67 expression remains controversial in gastric adenocarcinoma (GaC). The aim of this study was to investigate the expression and clinicopathologic and prognostic significance of Her2 and Ki-67 in resected GaC without distant metastasis. METHODS:Malignant tissues and clinicopathologic data were obtained from 195 patients with resected non-metastatic GaC. Immunohistochemistry staining was performed to examine the expression of Her2 and Ki-67; their association with clinicopathologic factors were investigated using logistic regression, and their association with survival was explored using Kaplan-Meier analysis and Cox proportional hazards regression. RESULTS:Her2 was majorly expressed in cell membrane and Ki-67 in cell nucleus in non-metastatic GaC. Stronger Her2 expression was significantly associated with better tumor differentiation, neurovascular invasion, less advanced pathological tumor (pT) stage, and more advanced pathological node (pN) stage; while Ki-67 expression was not significantly associated with any investigated clinicopathologic factors. Patients with both negative Her2 and negative Ki-67 expression had poorer tumor differentiation, and more advanced pT and pathological tumor-node-metastasis (pTNM) stages; the association with pT and pTNM stages were further confirmed by multivariable analyses, especially in node-negative disease. Her2 or Ki-67 alone was not significantly associated with pTNM stage. A strongly positive (+++) Her2 expression was associated with poorer survival in multivariable analysis only (P?=?0.047); while Ki-67 or combined expression was not significantly associated with prognosis. CONCLUSIONS:In non-metastatic GaC, Her2 expression and combined expression of Her2 and Ki-67 were associated with several clinicopathologic factors including tumor differentiation and stage, and only a +++ Her2 expression was associated with poorer prognosis in multivariable analysis with marginal significance in this study; while Ki-67 alone had both limited clinicopathologic and prognostic values.

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Exosome Released FZD10 Increases Ki-67 Expression via Phospho-ERK1/2 in Colorectal and Gastric Cancer.

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Exosome Released FZD10 Increases Ki-67 Expression <i>via</i> Phospho-ERK1/2 in Colorectal and Gastric Cancer.

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