Trefoil factor 3 expression in epithelial ovarian cancer exerts a minor effect on clinicopathological parameters

Hoellen, Friederike; Kostara, Athina; Karn, Thomas; Holtrich, Uwe; El‐Balat, Ahmed; Otto, Mike; Rody, Achim; Hanker, Lars

doi:10.3892/mco.2016.994

Cited by 4 publications

(6 citation statements)

References 13 publications

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“…Furthermore, we examined whether variation in the expression of certain genes contributed more to this latent variable than others. Using a gene set enrichment analysis (GSEA), we found an enrichment of genes with substantial contribution to this factor involved in estrogen response , including AGR2 and TFF3 (Figure 5b) (Salmans et al, 2013; Hoellen et al, 2016). These results suggest that there are substantial shared signals between the two data modalities, echoing prior work (Gundersen et al, 2019).…”

Section: Resultsmentioning

confidence: 99%

Linking histology and molecular state across human tissues

Jones

Gundersen

Engelhardt

2022

Preprint

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Histological imaging and molecular profiling of human tissues both offer information-rich characterizations of biological structure and function. Each of these modalities has been used to characterize the organization and dysregulation of a variety of tissues and cell types. While large-scale studies of each modality in isolation have been conducted, it remains largely unknown the extent to which these two views of a tissue relate to one another. Understanding how cellular states are encoded in cellular morphology would increase the utility and interpretability of imaging data; conversely, understanding the state of the cells within histology images would give deeper insights into the types and states of cells that constitute these tissue samples. To this end, we jointly analyzed 13, 360 human tissue samples with paired bulk gene expression profiles and histology images across 935 donors from the Genotype and Tissue Expression (GTEx) Consortium v8 study. This analysis reveals relationships among gene expression and cellular morphology through shared sources of expression and morphological heterogeneity both within and between tissue types. We describe shared sources of variation including cell-type heterogeneity, sample ischemic time, and donor health and demographics. We find specific correlated effects in both morphology and transcription linked to specific donor characteristics, such as their use of mechanical ventilation. This paired understanding adds value to each data modality on their own by enabling a more precise characterization of the alternative modality in the absence of those data.

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Section: Resultsmentioning

confidence: 99%

Linking histology and molecular state across human tissues

Jones

Gundersen

Engelhardt

2022

Preprint

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“…Elevated expression levels of TFF1 and TFF3 have been shown to correlate with changes in Ca125 (progression) and endocrine therapy response rates in ovarian cancer (56). Moreover, TMAbased studies demonstrated a correlation between elevated TFF3 expression, better prognosis, and lower recurrence rates in OC, but these studies were not stratified by histotype (54,57). In a study by Kalloger et al on OC histotyping, the TFF3 gene was used to separate different epithelial ovarian cancer subtypes (31).…”

Section: Discussionmentioning

confidence: 99%

“…Identification of elevated TFF1 protein levels in diverse cancers such as pancreatic, colonic, and ovarian tumor tissues indicate a universal function in tumor progression via stimulation of cell migration, survival, invasiveness, and distant spread ( 36 , 37 ). The TFF3 gene has been shown to be an estrogen-regulated oncogene with prognostic value in estrogen-positive breast cancer and important contributor to gastric cancer progression ( 54 ). In addition, high TFF3 levels are associated with poor survival, recurrence and distant metastasis in colorectal cancer ( 55 ).…”

Section: Discussionmentioning

confidence: 99%

Trefoil factor family proteins as potential diagnostic markers for mucinous invasive ovarian carcinoma

Rönnerman

Pettersson²,

Nemes³

et al. 2023

Front. Oncol.

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IntroductionOvarian cancer (OC) is the leading cause of gynecological cancer-related death. Of the main OC histologic subtypes, invasive mucinous carcinomas (MC) account for only 3% of OC cases and are frequently associated with favorable prognosis. Nevertheless, MCs differ greatly from the other OC histotypes in clinical, pathological, and biological behavior. However, the origin and molecular pathogenesis of MC are not yet fully understood. Therefore, identification of novel diagnostic markers could potentially facilitate early diagnosis of OC, particularly the MC histotype, thereby leading to the development of histotype-specific treatment regimens and improved survival rates.MethodsIn the present study, Trefoil factor gene family members (TFF1, TFF2 and TFF3) were identified as MC histotype-specific biomarkers using RNA sequencing (RNA-seq) data for 95 stage I-II OCs. The diagnostic value of TFF1, TFF2 and TFF3 was then evaluated by immunohistochemistry on 206 stage I-II OCs stratified by histotype (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], clear cell carcinoma [CCC], and MC).ResultsWe showed significantly elevated intracytoplasmic protein expression levels for TFF1, TFF2 and TFF3 in MC samples, thereby revealing an association between expression of Trefoil factor gene family members and the MC histotype. Taken together, these findings suggest that the TFF proteins may play a pivotal role in tumor initiation and progression for the MC histotype.ConclusionTaken together, these findings suggest that the TFF proteins may play a pivotal role in tumor initiation and progression for the MC histotype. Moreover, these novel histotype-specific diagnostic biomarkers may not only improve patient stratification of early-stage ovarian carcinomas but may also be candidates for the development of molecular targeted therapies.

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“…On the contrary, a higher TFF3 expression was found in BOT mucinous histology and BOT with mixed histology, suggesting a potential function of the protein in these histological subtypes [37]. Expression analysis of TFF3 was performed in a cohort of 91 OC patients by Hoellen et al No significant difference in TFF3 expression was found based on age, FIGO stage or residual tumor; meanwhile, a significant correlation of TFF3 expression and grade was detected [48]. However, since few studies have been carried out on TFF3 expression and its role in EC and OC and, mostly, few studies have considered its prognostic value, TFF3 expression deserves further investigation.…”

Section: Discussionmentioning

confidence: 99%

“…The idea of analyzing the expression of Romo1 in EC and OC comes from the evidence of its role in the process of invasion and also the progression of cancer cells [35,48]. It is involved in normal cellular processes, such as cell proliferation, senescence, and death.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic and prognostic role of TFF3, Romo-1, NF-кB and SFRP4 as biomarkers for endometrial and ovarian cancers: a prospective observational translational study

Turan¹,

Vitale

Kahramanoğlu

et al. 2022

Arch Gynecol Obstet

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Purpose This study aimed to evaluate trefoil factor 3 (TFF3), secreted frizzled-related protein 4 (sFRP4), reactive oxygen species modulator 1 (Romo1) and nuclear factor kappa B (NF-κB) as diagnostic and prognostic markers of endometrial cancer (EC) and ovarian cancer (OC). Methods Thirty-one patients with EC and 30 patients with OC undergone surgical treatment were enrolled together with 30 healthy controls in a prospective study. Commercial ELISA kits determined serum TFF-3, Romo-1, NF-кB and sFRP-4 concentrations. Results Serum TFF-3, Romo-1 and NF-кB levels were significantly higher in patients with EC and OC than those without cancer. Regarding EC, none of the serum biomarkers differs significantly between endometrial and non-endometrioid endometrial carcinomas. Mean serum TFF-3 and NF-кB levels were significantly higher in advanced stages. Increased serum levels of TFF-3 and NF-кB were found in those with a higher grade of the disease. Regarding OC, none of the serum biomarkers differed significantly among histological subtypes. Significantly increased serum levels of NF-кB were observed in patients with advanced-stage OC than those with stage I and II diseases. No difference in serum biomarker levels was found between those who had a recurrence and those who had not. The sensibility and specificity of these four biomarkers in discriminating EC and OC from the control group showed encouraging values, although no one reached 70%. Conclusions TFF-3, Romo-1, NF-кB and SFRP4 could represent new diagnostic and prognostic markers for OC and EC. Further studies are needed to validate our results.

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Trefoil factor 3 expression in epithelial ovarian cancer exerts a minor effect on clinicopathological parameters

Cited by 4 publications

References 13 publications

Linking histology and molecular state across human tissues

Linking histology and molecular state across human tissues

Trefoil factor family proteins as potential diagnostic markers for mucinous invasive ovarian carcinoma

Diagnostic and prognostic role of TFF3, Romo-1, NF-кB and SFRP4 as biomarkers for endometrial and ovarian cancers: a prospective observational translational study

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