PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Biomarker stratification”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13Linked to original sources
PubMed2026

Systemic biomarkers of treatment response to methotrexate in people with painful knee osteoarthritis: A biological substudy of the PROMOTE randomised controlled clinical trial.

OBJECTIVE: Stratification of therapeutic responses may help identify efficacious therapies for osteoarthritis (OA). In the PROMOTE randomised trial, participants with elevated baseline high-sensitivity C-reactive protein (hs-CRP) showed greater pain reduction after methotrexate treatment. We set out to interrogate a broader panel of serum/plasma inflammatory response markers relevant to methotrexate actions as potential biomarkers of therapeutic effect. Our objectives were to: (i) characterize changes in these systemic markers during methotrexate treatment; determine whether (ii) baseline levels or (iii) changes in any marker during treatment were associated with treatment response; and (iv) compare these findings with the more established clinical inflammatory marker, hs-CRP. DESIGN: Plasma/serum samples from participants in PROMOTE's biological substudy were analysed for 35 inflammatory markers at baseline (pre-treatment) and at 6-months (post-treatment), by MesoScale V-plex multiplex assay. Those with paired biological and clinical data at both baseline and 6-months were included in the substudy analysis set. Relationships between markers and overall data structure were assessed by Pearson correlation and Principal Component analysis. Associations between markers (baseline levels or change over time) and change in average knee pain severity in past week (numerical rating scale, NRS) were evaluated by univariable linear regression, adjusting for baseline age, sex, and body mass index. Least Absolute Shrinkage and Selection Operator (LASSO) regression with bootstrap resampling enabled marker selection. Benjamini-Hochberg correction adjusted for multiple testing (Padj). RESULTS: 87 participants with paired blood marker and clinical data were eligible for substudy analysis. 18/35 markers were quantifiable and analysed. Systemic IL-8 and TNF-α levels decreased (Padj=0.015, 0.048 respectively) while IL-15 increased (Padj=0.033) with methotrexate treatment over 6-months. Analysing within this active treatment randomised arm, higher baseline IFN-γ was associated with greater reduction in NRS pain change (0.66 [0.01, 1.31], P=0.047), as was decreasing TNF-α over 6-months (2.25 [0.00, 4.5], P=0.049). LASSO identified higher IFN-γ, lower plasma IL-15 and IL-16, and younger age as the most important baseline predictors of pain improvement. hs-CRP was highly selected by LASSO for treatment response in both arms. In a secondary univariate treatment arm-by-biomarker interaction analysis, of the 19 markers, only hs-CRP showed consistent effects in adjusted models (at baseline, coeffic. 2.34 [0.53, 4.15], P=0.001; change over 6-months, (0.36 [0.06, 0.66], P=0.018). CONCLUSIONS: Blood measurement of IFN-γ, TNF-α, IL-15 and IL-16 as well as hs-CRP could act as potential markers to stratify the treatment response by average knee pain to methotrexate in knee osteoarthritis.

Humans↗
PubMedDate not supplied

N-terminal probrain natriuretic peptide as a predictor of short-term outcomes in acute myocardial infarction.

BACKGROUND: Risk stratification and prediction of high risk for mortality in patients with acute coronary syndromes is based on clinical evaluation, electrocardiogram, biochemical markers and various risk assessment scores. There is emerging evidence that N-terminal probrain natriuretic peptide possesses several characteristics of an ideal biomarker. In this study we looked into the role of N-terminal probrain natriuretic peptide in risk stratification and prediction of short-term events including mortality in patients presenting with acute coronary syndrome. METHODS AND RESULTS: A total of 120 consecutive patients admitted with a diagnosis of acute myocardial infarction, including both ST elevation myocardial infarction (n=80) and non-ST elevation myocardial infarction (n=40) were enrolled. Serum N-terminal probrain natriuretic peptide was measured using electrochemiluminiscence assay (Roche Diagnostics), on the Elecsys 2010 system. On two-dimentional echocardiography, modified Simpson's technique was used to measure the ejection fraction along with end-systolic volume. Various other demographic variables, echocardiographic parameters and risk scores were also assessed. Follow-up at day 30 included a two-dimentional echocardiographic evaluation and assessment for worsening heart failure, recurrent ischemia, and repeat hospitalization. Death due to cardiovascular cause by 30 days was also noted. The mean value of N-terminal probrain natriuretic peptide for the whole cohort was 2307 +/- 2287 pg/ml (271.4 +/- 269.1 pmol/L). For the purpose of comparative analysis, the median value was determined [1403 pg/ml (165 pmol/L)]. In patients having N-terminal probrain natriuretic peptide above median, the end-systolic volume was higher while ejection fraction was significantly lower at baseline (p<0.05). At 30 days follow-up, there was a further decline in ejection fraction from 47.7 +/- 11.4 to 43.9 +/- 9.9 (p<0.05), and clinical outcomes were worse in this group. There was a 5% mortality in the entire study group and all patients who died had N-terminal probrain natriuretic peptide above median. On multivariate logistic regression analysis, N-terminal probrain natriuretic peptide above median (OR=32.79, 95% CI 8.74-123.1, p<0.001) emerged as the strongest predictors of adverse outcomes, including 30-day mortality (p<0.001). CONCLUSIONS: N-terminal probrain natriuretic peptide emerged as a strong prognostic tool across the spectrum of acute myocardial infarction and had the strongest predictive value for short-term adverse outcomes including death.

Adult↗
PubMed2026

Transcriptome-based epigenetic screening identifies DNA hypermethylation signatures as prognostic biomarkers in oral squamous cell carcinoma.

Promoter DNA hypermethylation is a key epigenetic mechanism of gene silencing in cancer, yet the DNA hypermethylome of oral squamous cell carcinoma (OSCC) and its prognostic relevance remain poorly characterized. Here, we systematically identified and validated novel hypermethylated genes with prognostic significance in OSCC using a genome-wide discovery and multi-platform validation strategy. Candidate genes were first identified by pharmacologic demethylation combined with RNA sequencing across OSCC cell lines, then validated by quantitative RT-PCR, methylation-specific PCR, and bisulfite sequencing in OSCC cell lines, normal oral mucosa, and primary OSCC tumors, with independent confirmation in the TCGA-HNSC dataset. Immunohistochemistry confirmed protein-level silencing, and Kaplan-Meier survival analysis assessed prognostic significance across both cohorts. This pipeline identified five candidate genes, GPX3, ANG, CTGF, GPRC5B, and BAMBI, exhibiting cancer-specific promoter hypermethylation associated with transcriptional and protein silencing in OSCC. Validation in oral cavity tumor samples extracted from the TCGA-HNSC dataset confirmed tumor-specific hypermethylation and revealed significant inverse correlations between methylation and expression for GPX3, GPRC5B, and CTGF. Notably, CTGF hypermethylation was independently associated with poor overall survival in both cohorts (institutional cohort, p=0.03; oral tumor subset from TCGA-HNSC, p=0.01), and a combined ANG+CTGF methylation signature showed superior and reproducible prognostic performance across both platforms. Pathway analysis linked these genes to epithelial-mesenchymal transition and interferon response signaling. This study establishes the first validated DNA methylation biomarker panel for OSCC prognosis, identifying CTGF hypermethylation as a robust prognostic driver with translational potential for clinical risk stratification.

Humans↗
PubMed2005

Genetics of scleroderma: update on single nucleotide polymorphism analysis and microarrays.

PURPOSE OF REVIEW: Recent family, twin, and genetic association studies suggest a genetic basis for the susceptibility to systemic sclerosis or scleroderma. The purpose of this review is to summarize the results of genetic association and gene expression profiling studies from January 2004 to May 2005. RECENT FINDINGS: In the review period, only a handful reports on single nucleotide polymorphism analysis of candidate genes and transcriptional profiling have been published. SUMMARY: Currently, single nucleotide polymorphism association studies in systemic sclerosis use small sample sizes and have low reproducibility. To detect associations with candidate genes that confer a modest relative risk for disease in the general population, studies are needed with much larger sample sizes that also account for the effects of population stratification. Candidate genes or pathways identified through microarrays can be explored as potential biomarkers, used for molecular phenotyping of systemic sclerosis, or targeted for future genetic association studies.

DNA↗
PubMed2025

Patient stratification by genetic risk in Alzheimer's disease is only effective in the presence of phenotypic heterogeneity.

Case-only designs in longitudinal cohorts are a valuable resource for identifying disease-relevant genes, pathways, and novel targets influencing disease progression. This is particularly relevant in Alzheimer's disease (AD), where longitudinal cohorts measure disease "progression," defined by rate of cognitive decline. Few of the identified drug targets for AD have been clinically tractable, and phenotypic heterogeneity is an obstacle to both clinical research and basic science. In four cohorts (n = 7241), we performed genome-wide association studies (GWAS) and Mendelian randomization (MR) to discover novel targets associated with progression and assess causal relationships. We tested opportunities for patient stratification by deriving polygenic risk scores (PRS) for AD risk and severity and tested the value of these scores in predicting progression. Genome-wide association studies identified no loci associated with progression at genome-wide significance (&#x3b1; = 5&#xd7;10-8); MR analyses provided no significant evidence of an association between cognitive decline in AD patients and protein levels in brain, cerebrospinal fluid (CSF), and plasma. Polygenic risk scores for AD risk did not reliably stratify fast from slow progressors; however, a deeper investigation found that APOE &#x3b5;4 status predicts amyloid-&#x3b2; and tau positive versus negative patients (odds ratio for an additional APOE &#x3b5;4 allele = 5.78 [95% confidence interval: 3.76-8.89], P<0.001) when restricting to a subset of patients with available CSF biomarker data. These results provided no evidence for large-effect, common-variant loci involved in the rate of memory decline, suggesting that patient stratification based on common genetic risk factors for progression may have limited utility. Where clinically relevant biomarkers suggest diagnostic heterogeneity, there is evidence that a priori identified genetic risk factors may have value in patient stratification. Mendelian randomization was less tractable due to the lack of large-effect loci, and future analyses with increased samples sizes are needed to replicate and validate our results.

Alzheimer Disease↗
PubMed2005

Biomarkers in acute coronary syndromes and their role in diabetic patients.

Diabetic patients with acute coronary syndromes are at high risk for cardiovascular complications but risk stratification in these patients remains challenging. Regularly, diabetic patients have a less typical clinical presentation, which could lead to delayed diagnosis and subsequent delayed initiation of treatment. Since diabetic patients derive particular benefit from aggressive anti-platelet therapy, early diagnostic and therapeutic risk stratification of these patients is of critical importance to improve their adverse outcome. Although the electrocardiogram remains a pivotal diagnostic tool in the evaluation of patients suspected of having an acute coronary syndrome, only significant ST-segment changes provide reasonable prognostic information. Therefore, repeated assessment of circulating protein biomarkers represents a valuable diagnostic tool for improving efficacy and safety of decision-making in these patients. The combined use of biomarkers reflecting distinct pathophysiological aspects, such as myocardial necrosis, vascular inflammation, oxidative stress and neurohumoral activation, may significantly improve triage of patients with chest pain. These tools may identify those patients that are at particularly high risk for short-term and/or long-term cardiovascular events. Eventually, tailored medical and interventional treatment of diabetic patients should help to prevent these cardiac events in a cost-effective manner.

Acute Disease↗
PubMed2006

Patient-related variables predicting acute coronary syndrome following admission for chest pain of possible coronary origin.

OBJECTIVE: Improving risk stratification of patients experiencing acute chest pain with non-revealing electrocardiogram and cardiac biomarkers could reduce missed acute coronary syndrome and avoid unnecessary hospitalization. METHODS: We assessed the ability of situational, circumstantial, and other patient-related variables in predicting acute coronary syndrome in 921 consecutive patients randomly admitted to this medical department with chest pain of possible coronary origin. A reference group comprised 107 patients referred promptly to the coronary care unit with acute myocardial infarction. RESULTS: Acute coronary syndrome eventually developed in 219 (23.7%) patients. Age and proportions of male patients and those with diabetes, which were significantly lower in the heterogeneous chest pain group than in the reference group, did not differ when re-evaluation was performed between the latter group and the subgroup of patients who eventually developed acute coronary syndrome. Overweight and a family history of premature coronary artery disease remained significantly higher in the reference group, while prevalence of pre-existing coronary artery disease, previous coronary angiography, and coronary intervention remained significantly lower. Variables most significantly predictive of acute coronary syndrome resulted: pre-existing coronary artery disease [odds ratio (OR) 3.2; 95% confidence interval (CI) 2.17-4.71; P<0.001), older age (OR 1.35; 95% CI 1.17-1.57; P<0.001), male sex (OR 1.77; 95% CI 1.19-2.61; P=0.004), diabetes (OR 1.6; 95% CI 1.11-2.32; P=0.01), self-initiation of pain relief treatment before seeking medical help (OR 1.54; 95% CI 1.07-2.23; P=0.02), and conviction that hospitalization for acute coronary disease was mandatory (OR 1.46; 95% CI 1.03-2.07; P=0.03). CONCLUSIONS: Easily obtainable patient-related variables might improve risk stratification and assist physicians to decide on policy in the emergency department and upon hospitalization.

Acute Disease↗
PubMed2026

Identification of molecular subtypes in clear cell renal cell carcinoma based on chromatin regulators and tumor immune microenvironment profiling.

In the histological classification of renal cell carcinoma, clear cell renal cell carcinoma (ccRCC) accounts for the highest proportion and is the most common subtype. Despite advances in management, it continues to be associated with considerable incidence and mortality. Although surgery and systemic therapies are available, their efficacy is constrained by pronounced intratumoral heterogeneity and treatment resistance. Identifying robust biomarkers and clarifying the underlying biological mechanisms are therefore essential to improving diagnosis, risk stratification and therapeutic decision-making. In this work, we identified two ccRCC molecular subtypes displaying divergent chromatin regulator (CR) profiles and different clinical prognoses. Using the genes differentially expressed between these subgroups, we constructed a CR-related score (CRS) that effectively stratified patients according to survival. More analysis concluded that the low expression of CR was more linked with the immune-activated tumors, which encompassed the immune pathway enrichment, as well as the elevation of numerous immune cell subtypes. Moreover, elevated CRS was associated with improved immunotherapy responsiveness. Drug-sensitivity analyses nominated several candidate agents, and SMARCD3 knockdown in 786-O cells inhibited proliferation and migration and reduced sensitivity to masitinib. Collectively, these findings support the prognostic and therapeutic relevance of CR-related states in ccRCC and provide a framework for future experimental validation of chromatin-regulated tumor-immune interactions.

Humans↗
PubMed2026

Osteoarthritis phenotypes: advancing precision medicine through clinical, structural, and molecular stratification.

PURPOSE: Osteoarthritis (OA) is now understood as a heterogeneous syndrome driven by diverse biological, biomechanical, metabolic, genetic, and molecular mechanisms. This variability explains differences in disease progression and treatment response, challenging the traditional "one-size-fits-all" approach. This review highlights OA phenotyping as a key step toward precision medicine, focusing on clinical, structural, and molecular classifications that inform individualized care. METHODS: A narrative review was conducted using a non-systematic search of major databases and Osteoarthritis Research Society International sources (2010-2026). Evidence was thematically synthesized across clinical, imaging, and molecular domains to characterize OA phenotypes and their potential relevance to precision medicine. RESULTS: Multiple OA phenotypes were identified: inflammatory, metabolic, biomechanical, cartilage-subchondral, pain-sensitization, and aging/senescence. These exhibit distinct clinical features, risk factors, and therapeutic responses. Imaging-based phenotypes (e.g., inflammatory, meniscus-cartilage, subchondral bone, atrophic, hypertrophic) and molecular endotypes (low turnover, structural damage, systemic inflammation) further refine stratification. Pain-structure discordance is notable in sensitization phenotypes and may predict poorer surgical outcomes. Joint-specific variations and emerging genomic and epigenetic insights underscore disease complexity. Advances in imaging, biomarkers, and machine learning may enable earlier detection and patient clustering, though clinical application remains limited. CONCLUSION: Phenotype- and endotype-based classification represents a critical advancement toward precision OA management. Tailored interventions based on stratification hold promise for improving outcomes; however, clinical translation remains limited by overlapping phenotypes, lack of validated biomarkers, and inconsistent results from phenotype-driven trials. Wider clinical adoption requires standardized definitions, validation across joints, and integration of multimodal diagnostic tools into routine practice.

Humans↗
PubMed2001

Troponins in patients with acute coronary syndromes: biologic, diagnostic, and therapeutic implications.

The cardiac troponins have expanded the spectrum of detectable myocardial injury and enhanced the clinician's ability to identify patients with acute coronary syndromes who are at higher risk for death or recurrent ischemic events. Based on available data, it appears most likely that any reliably detected troponin elevation results from myocyte necrosis. This notion has served as the basis for the recent revision of diagnostic criteria for acute myocardial infarction based on cardiac troponin. Nevertheless, further research is necessary to conclusively refute the possibility that the release of cardiac troponins may also occur in the setting of reversible myocyte injury resulting from cellular ischemia. Such an investigation establishing biologic correlates of troponin elevation is likely to prove valuable in guiding diagnostic terminology as well as in therapy. For example, clinical research finding cardiac troponin elevation to be predictive of intracoronary thrombus and distal microvascular obstruction has been important to the evaluation of troponins for targeting powerful antiplatelet and antithrombin therapies. Whether related to irreversible or reversible injury, the cardiac troponins have blurred the traditional boundaries between unstable angina and myocardial infarction and have evolved as powerful tools for risk stratification and therapeutic decision-making.

Biomarkers↗
PubMed1998

A strategy for the use of cardiac injury markers (troponin I and T, creatine kinase-MB mass and isoforms, and myoglobin) in the diagnosis of acute myocardial infarction.

OBJECTIVE: To design a strategy for cardiac injury marker testing in the diagnosis of acute myocardial infarction. DESIGN: Prospective study. Group I (n=54 patients): evaluation of clinical performance. Specimens collected at 0, 3, 6, and 12 (+/-1.5) hours after presentation. World Health Organization criteria were used for diagnosis of acute myocardial infarction. Group II (n=57 patients): evaluation of temporal evolution. Time intervals 0 to 1.5, 1.5 to 4.5, 4.5 to 7.5, and 7.5 to 13.5 hours. Patients identified by positive creatine kinase-MB (CK-MB) mass or myoglobin. Fourteen patients in Group I qualified for Group II. Hence, the total number of patients was 97. SETTING: A team of laboratorians and clinicians at the University of California, Davis, hospital assessed the clinical performance and temporal evolution of serial CK-MB isoform, troponin I, and troponin T results in comparison to parallel CK-MB mass and myoglobin results. MAIN OUTCOME MEASURES: Group I: sensitivity, specificity, and positive and negative predictive values. Group II: the time interval of the first positive result for each cardiac injury marker. Strategy and conclusions were based on study results and a literature review. PARTICIPANTS: Emergency department patients with acute onset of chest pain and other complaints, possibly indicative of myocardial ischemia, who were under evaluation for admission. RESULTS: Twenty-seven cases of acute myocardial infarction were documented. Group I: troponin I had the highest specificity (100%) and the highest positive predictive value (100%); troponin I, troponin T, and CK-MB mass had the highest sensitivity (90.0%); and the negative predictive values of troponin I, troponin T, and CK-MB mass were comparable (97.8%, 97.6%, and 97.6%, respectively). Group II: early diagnosis (within 1.5 hours) was provided by both CK-MB isoforms and CK-MB mass, and then by myoglobin and troponins, in order of decreasing frequency. CONCLUSIONS: Creatine kinase-MB mass, myoglobin, and troponin I were selected as the cardiac injury markers of choice at our institution. The strategy calls for serial testing of myoglobin and CK-MB mass initially-and serially if warranted by heightened clinical suspicion--with troponin I added if indicated for (1) specific confirmation, (2) late presentation, or (3) risk stratification.

Biomarkers↗
PubMed2026

An international framework for clinical translation of molecular classifiers in osteosarcoma.

Despite well-recognized biological heterogeneity, osteosarcoma has been treated as a single disease for over four decades with minimal improvement in survival. Clinical features are inadequate for risk stratification, and no molecular classifiers guide therapy. An international working group evaluated candidate prognostic biomarkers for clinical translation. Pre-treatment circulating tumor DNA is positioned for clinical implementation, while additional classifiers warrant prospective validation. This work establishes a path to risk-adapted, biologically informed treatment.

Journal Article↗
PubMed2026

Mitochondria related gene signature serves as prognosis prediction and risk stratification of cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma (CHOL) is a highly aggressive biliary malignancy with poor clinical outcomes and limited effective prognostic biomarkers. Mitochondrial dysfunction participates in multiple oncological processes of CHOL, yet the prognostic roles of mitochondria&#x2011;related genes (MRGs) remain poorly understood. This study aimed to characterize MRGs expression in CHOL and develop a molecular prognostic model for predicting patient survival and guiding clinical management. METHODS: RNA sequencing (RNA-seq) and clinical data of CHOL were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) (GSE89748) databases. Differentially expressed MRGs were identified, and 10 machine learning algorithms were used to construct prognostic models. The optimal model (highest average C-index) was selected to establish a mitochondria-related risk score (MRRS), which was validated internally and externally. A nomogram integrating clinical factors and MRRS was developed, and biological mechanisms were explored via functional and immune analyses. RESULTS: A 3-MRG (MAP3K1, MRPL18, PYGB) prognostic signature was constructed, stratifying patients into high- and low-risk groups with significantly different overall survival. The model showed high predictive accuracy, with an area under the curve (AUC) up to 0.845, and MRRS was an independent prognostic factor. The signature was associated with mitochondrial pathways, and the high-risk group had distinct immune infiltration and mutation profiles. CONCLUSIONS: A validated MRG prognostic model effectively stratifies CHOL patients and has potential clinical value for prognosis prediction. Further validation in larger cohorts is needed to confirm its applicability.

Cholangiocarcinoma (CHOL)↗
PubMed2006

Profiling bladder cancer using targeted antibody arrays.

Bladder cancer is a common malignancy requiring a high degree of surveillance because of the frequent recurrences and the poor clinical outcome of invasive disease. To date, serum biomarkers for bladder cancer lack optimal sensitivity and specificity to assist in diagnosis and disease categorization. Here, we designed antibody arrays for bladder cancer by selecting antibodies against targets differentially expressed in bladder tumors. Serum protein profiles measured by an antibody array containing 254 antibodies discriminated bladder cancer patients from controls (n = 95) with a correct classification rate of 93.7%. A second independent antibody array containing 144 antibodies revealed that protein profiles provide predictive information by stratifying patients with bladder tumors (n = 37) based on their overall survival (P = 0.0479). In addition, serum proteins, such as c-met, that were top ranked at identifying bladder cancer patients were associated with pathological stage, tumor grade, and survival when validated by immunohistochemistry of tissue microarrays containing bladder tumors (n = 173). This study provides experimental evidence for the use of several integrated technologies strengthening the process of biomarker discovery. Serum protein profiles obtained by antibody arrays represent comprehensive means for bladder cancer diagnosis and clinical outcome stratification, which could potentially assist in selection of cancer patients who would benefit from early, individualized therapeutic intervention.

Adult↗
PubMed2003

Prognostic molecular markers for planning adjuvant chemotherapy trials in Dukes' B colorectal cancer patients: how much evidence is enough?

The benefit of postoperative adjuvant chemotherapy in patients with Dukes' B colorectal cancer is still uncertain and its routine use is not recommended. Prognostic biomarkers may be useful for identifying high-risk patients with resected, node-negative disease, and this stratification may represent an innovative strategy for designing adjuvant chemotherapy trials. Featured prognostic molecular markers can be divided into the following categories: cell proliferation indices (Ki-67, Mib-1, proliferating cell nuclear antigen); oncogenes/tumor suppressor genes [p53, K-ras, Deleted in Colorectal Cancer (DCC), Bcl-2, c-erbB2]; DNA repair (microsatellite instability); markers of angiogenesis (vascular count, vascular endothelial growth factor); markers of invasion/metastasis (plasminogen-related molecules, matrix metalloproteinases); and biochemical markers (thymidylate synthase). Studies that have investigated their prognostic role in Dukes' B colorectal cancer patients are reviewed here. Current data do not provide sufficient evidence for the incorporation of available prognostic biomarkers into clinical practice. However, a biomarker-based approach could be an effective strategy for improving results of postoperative adjuvant treatments in high-risk Dukes' B colorectal cancer patients. Markers of altered DCC function have shown promising prognostic role and sufficient prevalence in retrospective investigations and they deserve further assessment in prospective studies.

Biomarkers, Tumor↗