Cutoff Finder: A Comprehensive and Straightforward Web Application Enabling Rapid Biomarker Cutoff Optimization

Budczies, Jan; Klauschen, Frederick; Sinn, Bruno Valentin; Győrffy, Balázs; Schmitt, Wolfgang; Darb‐Esfahani, Silvia; Denkert, Carsten

doi:10.1371/journal.pone.0051862

Cited by 1,060 publications

(986 citation statements)

References 31 publications

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“…The cut-off points for age, the CRP/ALB ratio, and NLR were determined using the method reported by Budczies et al (25). TNM, tumor-node-metastasis; AJCC, American Joint Committee on Cancer; CI, confidence interval; CRP, C-reactive protein; ALB, albumin; NLR, neutrophil/lymphocyte ratio.…”

Section: Univariate Analysismentioning

confidence: 99%

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C‑reactive protein/albumin and neutrophil/lymphocyte ratios and their combination predict overall survival in patients with gastric cancer

et al. 2017

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Abstract. Multiple studies have reported the prognostic association of certain inflammatory factors with various types of cancer. The present study assessed the prognostic value of the C-reactive protein (CRP)/albumin (Alb) ratio and the neutrophil/lymphocyte ratio (NLR), separately and in combination, in gastric cancer (GC). A total of 337 cases pathologically diagnosed with gastric adenocarcinoma were retrospectively evaluated. The clinicopathological and prognostic relevance of the CRP/Alb ratio and NLR and their combination were analyzed. The optimal cut-off values of the CRP/Alb ratio and NLR were 0.38 and 3.14, respectively. High CRP/Alb ratio (≥0.38) and NLR (≥3.14) values were associated with increased tumor invasion, more distant metastasis and a more advanced tumor-node-metastasis stage (all P<0.05). In addition, a high NLR value was also associated with increased tumor size (P= 0.02). The CRP/Alb ratio (≥0.38/<0.38) and NLR (≥3.14/<3.14) were independent prognostic factors for overall survival time (OS) in GC by multivariate analysis (P= 0.005 and P= 0.001). Using the CRP/Alb ratio and NLR classification, patients were stratified into three subgroups with different OS time (P<0.001), which were identified as independent prognostic variables in multivariate analysis (P<0.001). The present study demonstrated that the CRP/Alb ratio and NLR were independent prognostic factors for OS in patients with GC. The combination of these indexes was associated with significant prognostic value and may further stratify prognosis. IntroductionGastric cancer (GC) is one of the most common types of tumor globally. In 2015, GC had the second highest incidence and rate of mortality among cancer patients in China (1). Due to the rapid progression of GC and the absence of early specific symptoms and signs, the majority of patients are diagnosed at the late stage of gastric carcinoma (2-5). At present, surgery is the preferred treatment for patients without distant metastasis, and postoperative metastasis and recurrence are the predominant causes of mortality (3,5). Although disease-free and overall survival (OS) may be improved by postoperative chemotherapy and radiotherapy, the prognosis of GC remains poor (3,6). Identifying simple but effective prognostic markers for GC remains an important aim for researchers.Inflammation occurs in various types of tumor, and serves a crucial function in tumor development and distant metastasis (7-10). Previous studies have indicated that inflammation is associated with the formation of the tumor microenvironment by inflammatory mediators, including vasoactive amines and cytokines (11-13). The C-reactive protein (CRP)/albumin (Alb) ratio is used as a novel inflammation-based prognostic indicator in multiple types of tumor. Previous studies have demonstrated the prognostic value of CRP/Alb ratio in colorectal (14) and esophageal cancer (15), hepatocellular carcinoma (16), and renal (17) and pancreatic cancer (18). Another important inflammatory marker is the neutrophil/lymphocyte ratio (...

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Section: Univariate Analysismentioning

confidence: 99%

“…OS was defined as the time interval between diagnosis and mortality due to GC or the last follow-up. The optimal cut-off points for continuous prognostic indices were determined using the method reported by Budczies et al (25). Survival curves were constructed using the Kaplan-Meier method.…”

Section: Introductionmentioning

confidence: 99%

C‑reactive protein/albumin and neutrophil/lymphocyte ratios and their combination predict overall survival in patients with gastric cancer

et al. 2017

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“…41 (21) 20 (8) 12 (7) 5 (3) 2 (2) 0 126 (42) 84 (38) 46 (26) 20 (12) 8 (6) 2 (2) 0 12 (4) 8 (6) 2 (1) 1 (1) 0 0 44 (24) 20 (9) 11 (6) 5 (3) 2 (2) 0 141 (50) 91(46) 45 (25) 20 (12) 8 (6) 2 (2) Statistical analysis ROC curves were generated to obtain relevant cutoffs (22). Associations with disease-free and overall survival (DFS, from initial diagnosis to the diagnosis of local or distant recurrence; OS, from initial diagnosis to death) were analyzed (KaplanMeier plots, log-rank test).…”

Section: Translational Relevancementioning

confidence: 99%

A Case-Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic Markers in Male Breast Cancer

Humphries

Rajan

Droop

et al. 2017

Clinical Cancer Research

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Purpose: Breast cancer affects both genders, but is understudied in men. Although still rare, male breast cancer (MBC) is being diagnosed more frequently. Treatments are wholly informed by clinical studies conducted in women, based on assumptions that underlying biology is similar.Experimental Design: A transcriptomic investigation of male and female breast cancer was performed, confirming transcriptomic data in silico. Biomarkers were immunohistochemically assessed in 697 MBCs (n ¼ 477, training; n ¼ 220, validation set) and quantified in pre-and posttreatment samples from an MBC patient receiving everolimus and PI3K/mTOR inhibitor.Results: Gender-specific gene expression patterns were identified. eIF transcripts were upregulated in MBC. eIF4E and eIF5 were negatively prognostic for overall survival alone (log-rank P ¼ 0.013; HR ¼ 1.77, 1.12-2.8 and P ¼ 0.035; HR ¼ 1.68, 1.03-2.74, respectively), or when coexpressed (P ¼ 0.01; HR ¼ 2.66, 1.26-5.63), confirmed in the validation set. This remained upon multivariate Cox regression analysis [eIF4E P ¼ 0.016; HR ¼ 2.38 (1.18-4.8), eIF5 P ¼ 0.022; HR ¼ 2.55 (1.14-5.7); coexpression P ¼ 0.001; HR ¼ 7.04 (2.22-22.26)]. Marked reduction in eIF4E and eIF5 expression was seen post BEZ235/everolimus, with extended survival.Conclusions: Translational initiation pathway inhibition could be of clinical utility in MBC patients overexpressing eIF4E and eIF5. With mTOR inhibitors that target this pathway now in the clinic, these biomarkers may represent new targets for therapeutic intervention, although further independent validation is required.

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“…The study used the standardized, 3-endpoint, cut-off algorithm (pCR, DFS and OS) (23). The Ki-67 index and preoperative chemotherapy variables were divided into 3 subgroups each: ≤15, 15.1-35 and ≥35%, and pCR rates were 4.2, 12.8 and 29.0%, respectively (P<0.0005).…”

Section: Ki-67 Ohno Et Almentioning

confidence: 99%

Current status of the prognostic molecular biomarkers in breast cancer: A systematic review

et al. 2017

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Abstract. Biomarkers that facilitate the prediction of breast cancer prognosis can improve the quality of life in patients during the long period of illness and treatment. Particularly in recent years, with the advent of a more exhaustive analysis of genetic information and gene products, the molecular mechanisms at play during breast cancer have gradually become clearer. In the present study, a systematic review of the literature between 2009 and 2014 was conducted by searching for the keywords ʻbreast cancerʼ, ʻbiomarkersʼ, ʻdiagnosisʼ, ʻprognosisʼ and ʻdrug responseʼ to clarify the present state of knowledge regarding biomarkers. In the final analysis, 16 studies on biomarkers for the breast cancer prognosis were retrieved. From these, 7 biomarkers in 9 studies were found to be strongly reliable predictors of prognosis and a further 7 biomarkers in 7 studies were poorly reliable. The use of these prognostic biomarkers should increase the options available for treatment algorithms.

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Cutoff Finder: A Comprehensive and Straightforward Web Application Enabling Rapid Biomarker Cutoff Optimization

Cited by 1,060 publications

References 31 publications

C‑reactive protein/albumin and neutrophil/lymphocyte ratios and their combination predict overall survival in patients with gastric cancer

C‑reactive protein/albumin and neutrophil/lymphocyte ratios and their combination predict overall survival in patients with gastric cancer

A Case-Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic Markers in Male Breast Cancer

Current status of the prognostic molecular biomarkers in breast cancer: A systematic review

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