Biomarker Insights最新文献

Background: Procalcitonin (PCT) is recognized as an inflammatory biomarker, often elevated in COVID-19 pneumonia alongside other biomarkers. Understanding its association with severe outcomes and comparing its predictive ability with other biomarkers is crucial for clinical management.

Objectives: This retrospective multicenter observational study aimed to investigate the association between PCT levels and adverse outcomes in hospitalized COVID-19 patients. Additionally, it sought to compare the predictive performance of various biomarkers.

Design: The study analyzed data from the Society of Critical Care Medicine (SCCM) Viral Infection and Respiratory Illness Universal Study (VIRUS) registry, comprising COVID-19 patients hospitalized across multiple Mayo Clinic sites between March 2020 and June 2022.

Methods: A total of 7851 adult COVID-19 patients were included. Patients were categorized into 6 groups based on the worst WHO ordinal scale. Multivariate models were constructed using peak biomarker levels within 72 hours of admission, adjusted for confounders.

Results: Elevated PCT levels were independently associated with increased odds of adverse outcomes, including ICU admission (adjusted odds ratio [aOR] 1.32, 95%CI 1.27-1.38), IMV requirement (aOR 1.35, 95%CI: 1.28-1.42), and in-hospital mortality (aOR 1.30, 95%CI: 1.22-1.37). A 3.48-fold increase in IMV requirement and 3.55 times increase in in-hospital mortality were noted with peak PCT ⩾ 0.25 ng/ml. Similar associations were observed with other biomarkers like NLR (AUC 0.730), CRP, IL-6, LDH (AUC 0.800), and D-dimer (AUC 0.719). Models incorporating NLR, LDH, D-dimer, and PCT demonstrated the highest predictive accuracy, with a combined model exhibiting an area under the curve (AUC) of 0.826 (95%CI 0.803-0.849).

Conclusions: Higher PCT levels were significantly linked to worse outcomes in COVID-19 patients, emphasizing its potential as a prognostic marker. Biomarker-based predictive models, particularly those including PCT, showed promising utility for risk assessment and clinical decision-making. Further prospective studies are warranted to validate these findings on a larger scale.

Background: Prostate cancer (PCa) patients with biochemical recurrence (BCR) following radical prostatectomy or radiation therapy often present with very low prostate-specific antigen (PSA) levels (⩽0.5 ng/mL). Accurate detection of recurrence at such low levels is crucial for guiding treatment decisions.

Objectives: To assess the diagnostic efficacy of [¹⁸F]PSMA-1007 PET/MR (PSMA-PETMR) in detecting BCR of PCa in patients with very low PSA levels.

Design: A prospective study conducted between May 2021 and January 2023, with data subsequently analyzed retrospectively after a 2-year follow-up.

Methods: The cohort comprised 157 PCa patients with BCR, of whom 52 had PSA levels ⩽ 0.5 ng/mL and underwent PSMA-PETMR imaging. The imaging protocol incorporated multiparametric MRI (mpMRI) and PET acquisitions, with lesion classification following PSMA-RADS version 1.0. Detection rates of recurrent lesions, including local recurrence, lymph node metastasis, and skeletal metastasis, were evaluated.

Results: PSMA-PETMR exhibited a 63.5% detection rate for recurrent PCa at low PSA levels, surpassing traditional diagnostic methods. Thirty-four local recurrences, 12 metastatic lymph nodes, and 4 skeletal metastases were identified. Follow-up imaging enhanced the detection rate to 73.1% by reclassifying initially equivocal findings. PSMA-PETMR influenced clinical decision-making in 17% of patients by facilitating personalized treatment strategies.

Conclusion: PSMA-PETMR significantly improves the detection of recurrent PCa in patients with very low PSA levels, offering precise lesion localization and supporting personalized treatment approaches. Further studies are needed to optimize its clinical use and validate its long-term benefits.

Background: DNAJC12 (DnaJ heat shock protein family (Hsp40) member C12) encodes a member of the molecular chaperone Hsp40/DnaJ family, which are important protein folding and proteostasis regulators. Its role as a biomarker has been studied for a limited number of cancer types. Objectives: Here, we sought to investigate the potential of DNAJC12 mRNA and protein expression as a prognostic and predictive biomarker for breast cancer (BC).

Methods: Using in silico analysis and data from immunohistochemistry analysis (IHC) of 292 samples from patients with primary BC, we determined the expression pattern and prognostic value of DNAJC12 mRNA and protein expression.

Results: From online publicly available data, we were able to identify the transcripts of DNAJC12 as differentially expressed in patients with different clinicopathological characteristics, such as ER status (P < .001), PR status (P < .001), HER2 status (P < .010) and molecular subtype (P ⩽ .001). We also found DNAJC12 to be a potential prognostic predictor for overall survival, disease-free survival, and responsiveness to treatment; a low DNAJC12 mRNA expression is commonly associated with a worse prognosis. Using IHC analysis, we showed that low DNAJC12 protein-level expression is also associated with a worse prognosis in patients with all subtypes of BC and patients with Luminal BC, and its expression is significantly different between patients with different tumor size classifications (T1/T2 vs T3/T4; P = .013) or with different lymph node involvement (N0 vs N+; P = .005).

Conclusion: Our findings suggested a potential role for DNAJC12 as a prognostic and predictive biomarker for BC.

Background: There is an ongoing search for novel biomarkers of vascular dysfunction, extent of fibrosis and organ involvement in systemic sclerosis (SSc).

Objectives: We critically appraised the studies investigating the circulating concentrations of endothelin-1 in SSc patients and healthy controls.

Design: This was a systematic review with meta-analysis.

Data sources and methods: We searched electronic databases (PubMed, Scopus, and Web of Science) from inception to 15 June 2024. We assessed the risk of bias and the certainty of evidence using the JBI Critical Appraisal Checklist and GRADE, respectively.

Results: Endothelin-1 concentrations were significantly higher in SSc patients than in controls (26 studies; standardised mean difference, SMD = 0.98, 95% CI 0.73-1.23, P < .001; moderate certainty of evidence). In SSc patients, there were no significant differences in endothelin-1 concentrations between those with limited and diffuse cutaneous SSc (10 studies; SMD = 0.32, 95% CI -0.07 to 0.71 P = .11; very low certainty), and with and without digital ulcers (5 studies; SMD = 0.82, 95% CI -0.06 to 1.69, P = .066; very low certainty), pulmonary arterial hypertension (7 studies; SMD = 0.22, 95% CI -0.01 to 0.45, P = .066; very low certainty) or interstitial lung disease (3 studies; SMD = 0.09, 95% CI -0.18 to 0.35, P = .51; very low certainty). There was limited evidence in SSc patients with different video capillaroscopy pattern and telangiectasias. Subgroup and meta-regression analyses showed significant associations between the effect size and geographical location (studies investigating SSc patients and controls), year of publication (studies investigating SSc patients with limited and diffuse cutaneous SSc), and biological matrix assessed (studies investigating SSc patients with and without digital ulcers).

Conclusion: The results of this systematic review and meta-analysis highlight the potential role of endothelin-1 as a candidate biomarker of SSc. Further research is warranted to determine the utility of measuring endothelin-1 in SSc subgroups with different extent of fibrosis and organ involvement.

Registration: PROSPERO registration number - CRD42024566461.

Background: Immune checkpoint inhibitors (ICIs) hold a great promise in treatment of non-small cell lung cancer (NSCLC), while only a portion of patients benefited from the treatment, and others could not achieve optimal therapeutic effects from initial immunotherapy, even for those patients with PD-L1 (Programed cell death ligand 1) tested positive. However, the clinical markers for the selection of patients who will benefit from ICIs combination treatment beforehand are largely unknown.

Objectives: The purpose of this study was to explore the non-invasive biomarkers that can predict the efficacy of immune combination therapy in advanced/metastatic NSCLC patients.

Design: This study employed a retrospective cohort design to analyze dual predictive biomarkers in advanced non-small cell lung cancer (NSCLC) patients with immune combination therapy.

Method: An analysis was conducted on baseline information of 144 patients with advanced/metastatic NSCLC who received ICIs treatment from the November of 2018 to the January of 2023 in Beijing Chest Hospital. We established a scoring group chart to make quantitative prediction for overall survival (OS) and progression-free survival (PFS) based on 4 variables, and set up the nomogram model as well as Decision curve analysis (DCA) to assess clinical benefits of ICIs combination in treatment of patients with advanced/metastatic NSCLC.

Results: We found that serum globulin (GLB) >26.6 (g/L) (HR = 1.865, P = .002), absolute neutrophil counts (ANC) (10⁹/L) > 5 (HR = 2.146, P < .001), and bone metastasis (HR = 2.148, P < .001) were independent factors affecting the PFS of NSCLC patients. GLB > 26.6 (g/L) (HR = 1.741, P = .018), ANC (10⁹/L) >5 (HR = 1.807, P = .008), bone metastasis (HR = 1.651, P = .002), and PD-L1 Negative (HR = 2.432, P = .032) were independent factors affecting the OS of NSCLC patients. Same variables and cut-off value have good predictive efficacy in both PFS and OS.

Conclusion: In patients with advanced/metastatic NSCLC receiving ICIs combination treatment, the GLB, ANC, bone metastasis, and PD-L1 may serve as useful predictive markers for the prognosis of NSCLC patients with ICIs combination treatment.

[This corrects the article DOI: 10.1177/11772719231222111.].

Background: Reduced expression of thyroid hormone receptors (TRs) has been observed in various human malignancies, though its predictive value in hepatocellular carcinoma (HCC) remains uncertain.

Objective: To explore the predictive value of TRs in patients with hepatocellular carcinoma.

Design: The design was bioinformatic analysis combined with experimental study.

Methods: This study utilized Kaplan-Meier analysis of TR expression profiles from The Cancer Genome Atlas (TCGA). Expression levels of TRs in HCC and immune single cells were assessed using datasets from the Gene Expression Omnibus (GEO) and TCGA, analyzed with R software. Cox and logistic regression analyses were also conducted. Functional assays, including wound healing, CCK-8, and Transwell migration assays, were employed to investigate the role of the THRB gene.

Results: Kaplan-Meier analysis revealed that low THRB expression was significantly associated with reduced overall survival (OS), 5-year OS and disease-specific survival (DSS) in HCC patients (P < 0.05), while no significant association was found with THRA expression. Both Cox regression and logistic regression identified low THRB expression as an independent risk factor for HCC. THRB expression was significantly downregulated in tumor tissues compared to non-tumorous tissues in 3 GEO datasets and the TCGA profile. Functional assays confirmed that THRB inhibited HCC cell proliferation and migration. Additionally, single-cell RNA sequencing revealed that THRB was primarily expressed in CD16+ monocytes within tumor tissues and was associated with a poor OS rate.

Conclusion: Reduced THRB expression, but not THRA, was correlated with decreased OS in HCC patients.

Background: Latent TB infection (LTBI) affects one fourth of the global population. Currently, there is an absence of an optimal strategy for distinguishing between active tuberculosis (aTB) and LTBI. While some researchers have explored cytokines other than interferon-gamma (IFN-γ) as biomarkers, results have shown significant variability in their ability to differentiate between these conditions. This meta-analysis aims to evaluate the performance of activation phenotype and chemokine markers in distinguishing between aTB and LTBI.

Objectives: To assess the diagnostic accuracy of specific biomarkers (HLA-DR⁺ IFNγ⁺, CD38⁺ IFNγ⁺, MCP-1, and RANTES) in differentiating aTB from LTBI.

Design: This study was conducted in accordance with the PRISMA guidelines for systematic reviews and meta-analyses of diagnostic studies.

Data sources and methods: We conducted a comprehensive search of PubMed, Scopus, Sciences Direct, and Web of Science for primary studies published in English up to 2023. Studies were included if they reported sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC) for the biomarkers in question. We calculated pooled diagnostic sensitivity, specificity, DOR, and AUC, and used the summary receiver operating characteristic curve (SROC) to summarize the diagnostic performance of each biomarker.

Results: Sixteen studies involving 1696 participants were included in the analysis. Among them, 925 individuals were diagnosed with aTB, while 771 were classified as having LTBI. The specificity, sensitivity, DOR, and AUC for CD38⁺ IFNγ⁺, HLA-DR⁺ IFNγ⁺, RANTES, and MCP-1 were (0.97 [95% CI: 0.72-1.00], 0.90 [95% CI: 0.75-0.96], 291.863, and 0.9432), (0.90 [95% CI: 0.70-0.97], 0.83 [95% CI: 0.63-0.94], 41.819, and 0.8598), (0.68 [95% CI: 0.55-0.79], 0.72 [95% CI: 0.56-0.84], 5.733, and 0.7979), and (0.63 [95% CI: 0.54-0.72], 0.63 [95% CI: 0.50-0.75], 2.892, and 0.7290) respectively.

Conclusion: The findings indicate that CD38⁺ IFNγ⁺ and HLA-DR⁺ IFNγ⁺ demonstrated the highest diagnostic accuracy. Additional prospective research is necessary to identify the optimal combination of biomarkers to enhance diagnostic accuracy in clinical settings.

Registration: This review has been registered on PROSPERO: (CRD42023472091). Available from: https://www.crd.york.ac.uk/prospero/#recordDetails.

Background: Rheumatoid arthritis (RA) is complicated with interstitial lung disease (ILD). Gastroesophageal reflux disease is prevented by Helicobacter pylori infection and is a predisposing factor for idiopathic pulmonary fibrosis. However, the prevalence of H. pylori infection in RA patients with ILD has not been sufficiently investigated.

Objective: In this study, we analyzed anti-H. pylori antibodies in RA patients with ILD.

Design: Case-control observational study.

Methods: Anti-H. pylori antibodies were analyzed in the sera of RA patients using a commercially available enzyme-linked immunosorbent assay kit.

Results: The positivity of anti-H. pylori antibodies in RA with ILD (n = 30 [18.0%], P = .0227), usual interstitial pneumonia (n = 10 [14.3%], P = .0212), and airway disease (n = 30 [18.0%], P = .0227) was significantly lower than that of RA without chronic lung disease (n = 78 [27.5%]). The positivity of anti-H. pylori antibodies was also lower in RA with chronic lung disease (n = 68 [18.2%], P = .0059). Multiple logistic regression analyses showed that the presence of anti-H. pylori antibodies was independently and protectively associated with chronic lung disease in RA.

Conclusion: The seroprevalence of H. pylori was lower in RA with ILD. H. pylori infection prevented ILD in patients with RA by protecting them from gastroesophageal reflux disease.

Background: Acute mesenteric venous thrombosis (MVT) is rarely suspected as primary diagnosis in emergency departments and still carries an in-hospital mortality rate of above 20%.

Objectives: The aim of this study was to find differences in clinical and laboratory markers between patients with acute MVT and a control group of suspected but confirmed as not having any type of acute mesenteric ischaemia (AMI).

Design: Data was retrieved from the AMESI (Acute MESenteric Ischaemia) study. This international, multicenter prospective case-control study from 32 sites collected data on patients with suspected AMI during a 10-month period.

Methods: Independent factors associated with acute MVT were evaluated in a multivariable logistic regression analysis and expressed as odds ratios (OR) with 95% confidence intervals (CI).

Results: D-dimer was not significantly higher in MVT (n = 73) compared to non-AMI (n = 287) patients (median 7.0 mg/L vs 4.5 mg/L, P = .092). After entering BMI, atherosclerotic disease, history of venous thromboembolism, CRP, and D-dimer as covariates in a multi-variable logistic regression analysis, absence of atherosclerotic disease (OR 0.096, 95% CI 0.011-0.84; P = .034) and elevated D-dimer (OR 2.59/one SD increment, 95% CI 1.07-6.28; P = .034) were associated with MVT. The discriminative ability of D-dimer for MVT as assessed by area under the curve in the receiver operating characteristics analysis was 0.63 (95% CI 0.49-0.78).

Conclusion: Elevated D-dimer was associated with MVT, but the discriminative ability of D-dimer was poor. There is an urgent need to find a more accurate plasma biomarker for this condition.

Trial registration: NCT05218863 (registered 19.01.2022).