FOXM1 predicts disease progression in non-muscle invasive bladder cancer

Rinaldetti, Sébastien; Wirtz, Ralph M.; Worst, Thomas; Hartmann, Arndt; Breyer, Johannes; Dyrskjøt, Lars; Erben, Philipp

doi:10.1007/s00432-018-2694-5

Cited by 16 publications

(12 citation statements)

References 26 publications

(35 reference statements)

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“…Moreover, KM curves showed a significant association of the baseline reactivity levels of MAT2β-AAb with the time of KOA appearance. This statistical approach has been widely used in cancer biomarkers30–32 and it has been recently introduced in the rheumatology field 33 34. Interestingly, our results showed that higher baseline reactivity levels of this AAb result in a sooner development of radiographic KOA.…”

Section: Discussionmentioning

confidence: 61%

Discovery of an autoantibody signature for the early diagnosis of knee osteoarthritis: data from the Osteoarthritis Initiative

et al. 2019

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ObjectiveTo find autoantibodies (AAbs) in serum that could be useful to predict incidence of radiographic knee osteoarthritis (KOA).DesignA Nucleic-acid Programmable Protein Arrays (NAPPA) platform was used to screen AAbs against 2125 human proteins in sera at baseline from participants free of radiographic KOA belonging to the incidence and non-exposed subcohorts of the Osteoarthritis Initiative (OAI) who developed or not, radiographic KOA during a follow-up period of 96 months. NAPPA-ELISA were performed to analyse reactivity against methionine adenosyltransferase two beta (MAT2β) and verify the results in 327 participants from the same subcohorts. The association of MAT2β-AAb levels with KOA incidence was assessed by combining several robust biostatistics analysis (logistic regression, Receiver Operating Characteristic and Kaplan-Meier curves). The proposed prognostic model was replicated in samples from the progression subcohort of the OAI.ResultsIn the screening phase, six AAbs were found significantly different at baseline in samples from incident compared with non-incident participants. In the verification phase, high levels of MAT2β-AAb were significantly associated with the future incidence of KOA and with an earlier development of the disease. The incorporation of this AAb in a clinical model for the prognosis of incident radiographic KOA significantly improved the identification/classification of patients who will develop the disorder. The usefulness of the model to predict radiographic KOA was confirmed on a different OAI subcohort.ConclusionsThe measurement of AAbs against MAT2β in serum might be highly useful to improve the prediction of OA development, and also to estimate the time to incidence.

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Section: Discussionmentioning

confidence: 61%

Discovery of an autoantibody signature for the early diagnosis of knee osteoarthritis: data from the Osteoarthritis Initiative

et al. 2019

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“…In line with this, a higher WHO 1973 grade was associated with MKI67 and ERBB2 mRNA levels [ 20 ]. Similarly, FOXM1 mRNA expression was associated with a higher grade and stage as well as a 6 to 8-fold higher risk of progression in multivariable analysis ( p < 0.03) of the UROMOL study (n = 488), which could be validated in independent NMIBC cohorts (n = 277) in silico [ 27 ]. Further analysis revealed that proliferation as determined by FOXM1 mRNA expression was predictive for chemotherapy benefit in T1 NMIBC (n = 296) with patients having low FOXM1 expression having better outcomes, irrespective of instillation therapy, while patients with high FOXM1 expression benefitted from intravesical chemotherapy with mitomycin C [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Role of Survivin and Macrophage Infiltration Quantified on Protein and mRNA Level in Molecular Subtypes Determined by RT-qPCR of KRT5, KRT20, and ERBB2 in Muscle-Invasive Bladder Cancer Treated by Adjuvant Chemotherapy

Ecke

Kiani

Schlomm

et al. 2020

IJMS

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Objectives: Bladder cancer is a heterogeneous malignancy. Therefore, it is difficult to find single predictive markers. Moreover, most studies focus on either the immunohistochemical or molecular assessment of tumor tissues by next-generation sequencing (NGS) or PCR, while a combination of immunohistochemistry (IHC) and PCR for tumor marker assessment might have the strongest impact to predict outcome and select optimal therapies in real-world application. We investigated the role of proliferation survivin/BIRC5 and macrophage infiltration (CD68, MAC387, CLEVER-1) on the basis of molecular subtypes of bladder cancer (KRT5, KRT20, ERBB2) to predict outcomes of adjuvant treated muscle-invasive bladder cancer patients with regard to progression-free survival (PFS) and disease-specific survival (DSS). Materials and Methods: We used tissue microarrays (TMA) from n = 50 patients (38 males, 12 female) with muscle-invasive bladder cancer. All patients had been treated with radical cystectomy followed by adjuvant triple chemotherapy. Median follow-up time was 60.5 months. CD68, CLEVER-1, MAC387, and survivin protein were detected by immunostaining and subsequent visual inspection. BIRC5, KRT5, KRT20, ERBB2, and CD68 mRNAs were detected by standardized RT-qPCR after tissue dot RNA extraction using a novel stamp technology. All these markers were evaluated in three different centers of excellence. Results: Nuclear staining rather than cytoplasmic staining of survivin predicted DSS as a single marker with high levels of survivin being associated with better PFS and DSS upon adjuvant chemotherapy (p = 0.0138 and p = 0.001, respectively). These results were validated by the quantitation of BIRC5 mRNA by PCR (p = 0.0004 and p = 0.0508, respectively). Interestingly, nuclear staining of survivin protein was positively associated with BIRC5 mRNA, while cytoplasmic staining was inversely related, indicating that the translocation of survivin protein into the nucleus occurred at a discrete, higher level of its mRNA. Combining survivin/BIRC5 levels based on molecular subtype being assessed by KRT20 expression improved the predictive value, with tumors having low survivin/BIRC5 and KRT20 mRNA levels having the best survival (75% vs. 20% vs. 10% 5-year DSS, p = 0.0005), and these values were independent of grading, node status, and tumor stage in multivariate analysis (p = 0.0167). Macrophage infiltration dominated in basal tumors and was inversely related with the luminal subtype marker gene expression. The presence of macrophages in survivin-positive or ERBB2-positive tumors was associated with worse DSS. Conclusions: For muscle-invasive bladder cancer patients, the proliferative activity as determined by the nuclear staining of survivin or RT-qPCR on the basis of molecular subtype characteristics outperforms single marker detections and single technology approaches. Infiltration by macrophages detected by IHC or PCR is associated with worse outcome in defined subsets of tumors. The limitations of this study are the retrospective nature and the limited number of patients. However, the number of molecular markers has been restricted and based on predefined assumptions, which resulted in the dissection of muscle-invasive disease into tumor–biological axes of high prognostic relevance, which warrant further investigation and validation.

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“…Several novel multi-gene-based signatures and single biomarkers for prediction of progression of NMIBC to MIBC have been reported in recent years and comparison of the 13-mRNA signature with them was conducted in our study (14)(15)(16)(17)(18). The ROC curves indicated that the performance of the 13-mRNA signature was similar to that of the 12-gene progression score model, and superior to that of the 5-gene model and three other single-gene biomarkers in two GEO datasets.…”

Section: Discussionmentioning

confidence: 99%

Identification of a 13‑mRNA signature for predicting disease progression and prognosis in patients with bladder cancer

et al. 2019

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There are no reliable criteria to assess risk of progression of non-muscle invasive bladder cancer to muscle invasive bladder cancer. The aim of the present study was to identify potential markers based on gene expression profiling to improve predictive power of disease progression and prognosis in patients with bladder cancer. In the present study, we screened seventy-three differentially expressed genes by analyzing bladder cancer samples with or without progression. Forty-seven prognosis-related genes were screened, 13 of which were identified to build a progression-associated gene signature using the LASSO regression method. Based on this 13-mRNA signature, patients were divided into high-and low-risk groups, with different prognostic outcomes. The gene signature was an independent prognostic factor for overall survival. Receiver operating characteristic analysis suggested that the signature performed well in the validation cohort and its predictive power outperformed other several published signatures. CTHRC1, MMP11, AEBP1, SNCAIP, COL1A1 and S100A8 were identified as hub genes and their expression levels were detected using reverse transcriptase-quantitative polymerase chain reaction. The expression of CTHRC1 was elevated in aggressive bladder cancer compared with non-invasive type, which suggests CTHRC1 may be a valuable biomarker for prediction of prognosis and progression of bladder cancer. Collectively, this 13-mRNA signature may be useful in predicting disease progression and prognosis, thereby contributing to individualized management of patients with bladder cancer.

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FOXM1 predicts disease progression in non-muscle invasive bladder cancer

Cited by 16 publications

References 26 publications

Discovery of an autoantibody signature for the early diagnosis of knee osteoarthritis: data from the Osteoarthritis Initiative

Discovery of an autoantibody signature for the early diagnosis of knee osteoarthritis: data from the Osteoarthritis Initiative

Prognostic Role of Survivin and Macrophage Infiltration Quantified on Protein and mRNA Level in Molecular Subtypes Determined by RT-qPCR of KRT5, KRT20, and ERBB2 in Muscle-Invasive Bladder Cancer Treated by Adjuvant Chemotherapy

Identification of a 13‑mRNA signature for predicting disease progression and prognosis in patients with bladder cancer

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