Reporting recommendations for tumor MARKer prognostic studies (REMARK)

Biometric Research Branch, National Cancer Institute, Bethesda, MD, USA.
Journal of Clinical Oncology (Impact Factor: 18.43). 10/2006; 23(36):9067-72. DOI: 10.1200/JCO.2004.01.0454
Source: PubMed


Despite years of research and hundreds of reports on tumour markers in oncology, the number of markers that have emerged as clinically useful is pitifully small. Often initially reported studies of a marker show great promise, but subsequent studies on the same or related markers yield inconsistent conclusions or stand in direct contradiction to the promising results. It is imperative that we attempt to understand the reasons that multiple studies of the same marker lead to differing conclusions. A variety of methodological problems have been cited to explain these discrepancies. Unfortunately, many tumour marker studies have not been reported in a rigorous fashion, and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalisability of the study results. The development of guidelines for the reporting of tumour marker studies was a major recommendation of the US National Cancer Institute and the European Organisation for Research and Treatment of Cancer (NCI-EORTC) First International Meeting on Cancer Diagnostics in 2000. Similar to the successful CONSORT initiative for randomised trials and the STARD statement for diagnostic studies, we suggest guidelines to provide relevant information about the study design, preplanned hypotheses, patient and specimen characteristics, assay methods, and statistical analysis methods. In addition, the guidelines suggest helpful presentations of data and important elements to include in discussions. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and understand the context in which the conclusions apply.

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Available from: Lisa M Mcshane, Sep 10, 2014
    • "Please cite this article in press as: Alsubhi, N., et al., Chk1 phosphorylated at serine 345 is a predictor of early local recurrence and radio-resistance in breast cancer, Molecular Oncology (2015), criteria (McShane et al., 2005). Ethical approval for the study was granted by Nottingham Research Ethics committee 2 under the title " Development of a molecular genetic classification of breast cancer " (C202313). "
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    ABSTRACT: Radiation-induced DNA damage activates the DNA damage response (DDR). DDR up-regulation may predict radio-resistance and increase the risk of early local recurrence despite radiotherapy in early stage breast cancers. In 1755 early stage breast cancers, DDR signalling [ATM, ATR, Ckh1, Chk1 phosphorylated at serine 345, Chk2, p53], base excision repair [PARP1, POLß, XRCC1, FEN1, SMUG1], non-homologous end joining (Ku70/Ku80, DNA-PKcs) and homologous recombination [RAD51, BRCA1, γH2AX, BLM, WRN, RECQL5, PTEN] protein expression was correlated to time to early local recurrence. Pre-clinically, radio sensitization by inhibition of Chk1 activation by ATR inhibitor (VE-821) and inhibition of Chk1 (V158411) were investigated in MDA-MB-231 (p53 mutant) and MCF-7 (p53 wild-type) breast cancer cells. In the whole cohort, 208/1755 patients (11.9%) developed local recurrence of which 126 (61%) developed local recurrence within 5 years of initiation of primary therapy. Of the 20 markers tested, only pChk1 and p53 significantly associated with early local recurrence (p value = 0.015 and 0.010, respectively). When analysed together, high cytoplasmic pChk1-nuclear pChk1 (p=0.039), high cytoplasmic pChk1-p53 (p= 0.004) and high nuclear pChk1-p53 (p=0.029)co-expression remain significantly linked to early local recurrence. In multivariate analysis, cytoplasmic pChk1 level independently predicted early local recurrence (p=0.025). In patients who received adjuvant local radiotherapy (n=949), p53 (p=0.014) and high cytoplasmic pChk1-p53 (p=0.017) remain associated with early local recurrence. Pre-clinically, radio-sensitisation by VE-821 or V158411 was observed in both MCF-7 and MDA-MB-231 cells and was more pronounced in MCF-7 cells. We conclude that pChk1 is a predictor of radio-resistance and early local recurrence.
    Molecular oncology 09/2015; In Press. DOI:10.1016/j.molonc.2015.09.009 · 5.33 Impact Factor
    • "AR, ER (α and β), and PR-expression were determined on tissue micro-arrays (TMAs) and correlated to prospectively collected progression free survival (PFS) and overall survival (OS) data. Study execution and reporting was performed in adherence to REMARK criteria [16] "
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    ABSTRACT: Androgen receptor (AR), estrogen receptor α and β (ERα, ERβ), and progesterone receptor (PR) are potential therapeutic targets in epithelial ovarian cancer. In this study we evaluate the prognostic value of these hormone receptors in ovarian cancer patients. In a prospective multicenter randomized controlled phase II trial 196 ovarian cancer patients were randomized to carboplatin/docetaxel±celecoxib. Of 121 patients sufficient tumor tissue was available for hormone receptor analysis. Tissue micro-arrays were stained for AR, ERα, ERβ, and PR. Cluster analysis was performed to identify subgroups based on hormone receptor expression profile. Receptor expression was correlated to progression-free survival (PFS) and overall survival (OS) in uni- and multivariate analysis. AR, ERα, ERβ, and PR were expressed in respectively 10%, 31%, 73%, and 19%. In patients with synchronous metastasis tissue available (n=69 patients), discordant receptor expression was observed in 9-32%. ERβ-expression was associated with poor PFS and OS (hazard ratios 1.88 and 1.92). Clustering analysis revealed a subgroup with hormone receptor negative disease that had a favorable PFS and OS. Hormone receptors are expressed in the majority of ovarian cancer tumors and may serve as therapeutic targets. Clustering analysis can reveal subgroups with different outcome, which may prove valuable in selecting patients for endocrine therapy. Copyright © 2015. Published by Elsevier Inc.
    Gynecologic Oncology 06/2015; 138(3). DOI:10.1016/j.ygyno.2015.06.032 · 3.77 Impact Factor
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    • "The case series included 42 patients who developed distant metastasis within 5 years of surgery and 50 patients who were free of distant metastasis for at least 5 years, all were selected so they had a similar age and tumor size. The same case series has been investigated at the gene expression level, and clinico-pathological features have been already reported (Callari et al, 2014) complying with the Remark guidelines (McShane et al, 2005). A written informed consent signed by each patient authorised the use of material left over from the diagnosis for research purposes. "
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    ABSTRACT: Breast cancer clinical outcome is affected by tumor molecular features, and the identification of subtype-specific prognostic biomarkers is relevant for breast cancer translational research. Gene expression signatures proved to be able to complement prognostic information provided by classical clinico-pathological features. Recently, microRNAs (miRNAs) have been causally linked to tumorigenesis and cancer progression and have been associated with patient outcome, also in breast cancer. MicroRNAs associated with the development of distant metastasis were identified in a cohort of 92 ESR1+/ERBB2- lymph node-negative breast cancers from patients not receiving adjuvant treatment. Results were confirmed and further investigated in a total of 1246 miRNA and gene expression profiles of the Molecular Taxonomy of Breast Cancer International Consortium data set. Moderated t-test, univariable and multivariable Cox regression models were used for statistical analyses. miR-30e* was identified as independent protective prognostic factor in lymph node-negative untreated patients with ESR1+/ERBB2- tumours and retained a significant association with a good prognosis in treated patients with the same tumor subtype as well as in the ERBB2+ subtype, but not in ESR1-/ERBB2- tumours. We highlighted a relevant and subtype-specific role in breast cancer for miR-30e* and demonstrated that adding miRNA markers to gene signatures and clinico-pathological features can help for a better prognostication.British Journal of Cancer advance online publication, 9 June 2015; doi:10.1038/bjc.2015.206
    British Journal of Cancer 06/2015; 113(2). DOI:10.1038/bjc.2015.206 · 4.84 Impact Factor
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