Background
The development of a non‐invasive and accurate diagnostic biomarker for endometriosis is urgently needed.
Objective
Evaluate the diagnostic accuracy of serum cancer antigen 125 (CA 125) ...for endometriosis.
Search strategy
We searched EMBASE, MEDLINE, and Web of Science from inception to January 2016.
Selection criteria
Diagnostic accuracy studies of serum CA 125 (index test) for histologically confirmed endometriosis (reference standard) were included.
Data collection and analysis
Two authors independently selected trials, extracted study characteristics and data. Methodological quality was assessed using Quality Assessment of Comparative Diagnostic Accuracy Studies (QUADAS‐2) checklist.
Main results
Twenty‐two studies (16 cohort, six case‐control), 3626 participants, were identified. Bivariate hierarchical models were used to pool accuracy data of 14 studies (2920 participants) using CA 125 ≥ 30 units/ml. Pooled specificity was 93% (95% CI 89–95%) and sensitivity 52% (95% CI 38–66%). CA 125 was significantly more sensitive for the diagnosis of moderate or severe endometriosis compared with minimal disease (63%, 95% CI 47–77% versus 24%, 95%CI 19–32%, P‐value = 0.001).
Conclusions
CA 125 performs well as a rule‐in test facilitating expedited diagnosis and ensuring investigation and treatment can be confidently tailored for the management of endometriosis. Unfortunately, a negative test, CA 125 < 30 units/ml, is unable to rule out endometriosis.
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Blood test CA 125: a rule‐in test for the diagnosis of women presenting with symptoms of endometriosis
Tweetable
Blood test CA 125: a rule‐in test for the #diagnosis of women presenting with symptoms of #endometriosis.
This article includes Author Insights, a video available at https://vimeo.com/rcog/authorinsights14055
Background
Circular RNAs (circRNAs) are structural ubiquitous RNA molecules. Accumulating evidences have elucidated that circRNAs play essential roles in the pathogenesis of diseases including ...cancers. Exosomal circRNAs are those circRNAs stably existing in exosomes and having high clinical values as novel potential diagnostic biomarkers of many diseases. Gastrointestinal (GI) malignancies, including pancreatic cancer, colorectal cancer, hepatocellular carcinoma (HCC), and gastric cancer, are leading causes of mortality worldwide and a major global health burden. However, no ideal tumor biomarkers of screening early GI cancers are currently available.
Methods
We collected data through Web of Science. The search terms used were as follows: circular RNA, circRNA, exosomes, exosomal circRNAs, biomarkers, gastrointestinal malignancies, pancreatic cancer, hepatocellular carcinoma, HCC, gastric cancer, colorectal cancer, physiological functions, biogenesis, molecular mechanism. Only articles published in English were included.
Results
We found that several circRNAs and exosomal circRNAs have been used as potential biomarkers to screen GI cancers including pancreatic cancer (hsa_circ_0001649, circ_0007534, circ_0030235, circRHOT1, circZMYM2, circ‐LDLRAD3, chr14:101402109‐101464448C, chr4:52729603‐52780244C, circ‐IARS, and circ‐PDE8A), HCC (circSETD3, circADAMTS13, hsa_circ_0007874, hsa_circ_104135, circFBLIM1, cSMARCA5, circRNA‐100338, and circPTGR1), colorectal cancer (hsa_circ_0001178, hsa_circ_0000826, hsa_circ_0004771, circDDX17, circITGA7, and circHIPK3), and gastric cancer (hsa_circ_0074362, circNRIP1, circAKT3, circ‐DONSON, circPSMC3, circ‐KIAA1244, circPVRL3, circPVT1, hsa_circ_0000096, ciRS‐133, hsa_circ_0001017, and hsa_circ_0061276).
Conclusion
CircRNAs and exosomal circRNAs have the potential high clinical diagnostic values for GI malignancies.
Changes in plasma and fecal metabolomes in colorectal cancer (CRC) progression (normal-adenoma-CRC) remain unclear. Here, plasma and fecal samples were collected from four independent cohorts of ...1,251 individuals (422 CRC, 399 colorectal adenoma CRA, and 430 normal controls NC). By metabolomic profiling, signature plasma and fecal metabolites with consistent shift across NC, CRA, and CRC are identified, including CRC-enriched oleic acid and CRC-depleted allocholic acid. Oleic acid exhibits pro-tumorigenic effects in CRC cells, patient-derived organoids, and two murine CRC models, whereas allocholic acid has opposing effects. By integrative analysis, we found that oleic acid or allocholic acid directly binds to α-enolase or farnesoid X receptor-1 in CRC cells, respectively, to modulate cancer-associated pathways. Clinically, we establish a panel of 17 plasma metabolites that accurately diagnoses CRC in a discovery and three validation cohorts (AUC = 0.848–0.987). Overall, we characterize metabolite signatures, mechanistic significance, and diagnostic potential of plasma and fecal metabolomes in CRC.
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•Altered plasma and fecal metabolites in CRC and colorectal adenoma are identified•CRC-enriched oleic acid and CRC-depleted allocholic acid are key metabolites in CRC•Metabolites bind to tumor cell receptor to modulate downstream oncogenic pathways•Plasma metabolites are potential diagnostic biomarkers of CRC and adenoma
Sun et al. reveal signature plasma and fecal metabolites across colorectal cancer (CRC) progression including CRC-enriched oleic acid and CRC-depleted allocholic acid, and decipher their mechanistic role in colorectal tumorigenesis. Sun et al. also demonstrate the diagnostic potential of plasma metabolites in CRC or adenoma patients from four independent cohorts.
Exosomes are membranous vesicles containing various biomolecules including lncRNAs which are involved in cellular communication and are secreted from many cells including cancer cells. In our study, ...investigated the exosomal GAS5 and lincRNA-p21 lncRNA levels in urine samples from 30 patients with prostate cancer (PCa) and 49 patients with benign prostatic hyperplasia. Quantification of lncRNA molecules was performed by real-time PCR. We observed a significant difference in the exosomal lincRNA-p21 levels between PCa and BPH patients whereas the GAS5 levels did not reveal a difference. Our data suggest that the discriminative potential of exosomal lincRNA-p21 levels may help to improve the diagnostic prediction of the malignant state for patients with PCa.
Urinary microRNAs (miRNAs) are emerging as clinically useful tool for early and non‐invasive detection of various types of cancer including bladder cancer (BCA). In this study, 205 patients with BCA ...and 99 healthy controls were prospectively enrolled. Expression profiles of urinary miRNAs were obtained using Affymetrix miRNA microarrays (2578 miRNAs) and candidate miRNAs further validated in independent cohorts using qRT‐PCR. Whole‐genome profiling identified 76 miRNAs with significantly different concentrations in urine of BCA compared to controls (P < 0.01). In the training and independent validation phase of the study, miR‐31‐5p, miR‐93‐5p and miR‐191‐5p were confirmed to have significantly higher levels in urine of patients with BCA in comparison with controls (P < 0.01). We further established 2‐miRNA‐based urinary DxScore (miR‐93‐5p, miR‐31‐5p) enabling sensitive BCA detection with AUC being 0.84 and 0.81 in the training and validation phase, respectively. Moreover, DxScore significantly differed in the various histopathological subgroups of BCA and decreased post‐operatively. In conclusion, we identified and independently validated cell‐free urinary miRNAs as promising biomarkers enabling non‐invasive detection of BCA.
Recent sequencing studies demonstrated the MYD88 L265P mutation in more than 70% of primary central nervous system lymphomas (PCNSL), and the clinical significance of this mutation has been proposed ...as diagnostic and prognostic markers in PCNSL. In contrast, mutational analyses using cell‐free DNAs have been reported in a variety of systemic lymphomas. To investigate how sensitively the MYD88 L265P mutation can be identified in cell‐free DNA from PCNSL patients, we carried out droplet digital PCR (ddPCR) and targeted deep sequencing (TDS) in 14 consecutive PCNSL patients from whom paired tumor‐derived DNA and cell‐free DNA was available at diagnosis. The MYD88 L265P mutation was found in tumor‐derived DNA from all 14 patients (14/14, 100%). In contrast, among 14 cell‐free DNAs evaluated by ddPCR (14/14) and TDS (13/14), the MYD88 L265P mutation was detected in eight out of 14 (ddPCR) and in 0 out of 13 (TDS) samples, implying dependence on the detection method. After chemotherapy, the MYD88 L265P mutation in cell‐free DNAs was traced in five patients; unexpectedly, the mutations disappeared after chemotherapy was given, and they remained undetectable in all patients. These observations suggest that ddPCR can sensitively detect the MYD88 L265P mutation in cell‐free DNA and could be used as non‐invasive diagnostics, but may not be applicable for monitoring minimal residual diseases in PCNSL.
Our findings might provide new perspectives on the utility of ddPCR‐based detection of L265P MyD88 mutations in cell‐free DNAs as a non‐invasive diagnostic marker of PCNSL.
Background
Basal cell carcinoma can simulate melanoma and specific dermoscopic criteria have not yet been defined in a large cohort.
Objective
To identify dermoscopic “trump” characteristics for ...differential diagnosis, identify cluster groups and assess the clinical impact of this study's findings.
Methods
Retrospective, multicentric comparative study of atypical, non‐facial basal cell carcinoma (≥1 seven‐point checklist criteria) and melanoma (with at least one BCC criteria) at dermoscopy. Observed dermoscopic features were used to develop a proposed score. Lesion clusters were defined with hierarchical analysis. Clinical impact was assessed with a blinded reader study following this study's results.
Results
A total of 146 basal cell carcinoma and 76 melanoma were included. Atypical vascular pattern was common to most lesions (74.5%). Twelve trump features were included in the proposed score (sensitivity 94.1% and specificity 79.5%). Cluster analysis identified 3 basal cell carcinoma and 3 melanoma clusters. Findings improved overall diagnostic accuracy and confidence (26.8% and 13.8%, respectively; p < 0.001).
Conclusions
These findings support the notion that atypical vascular pattern should be considered a shared feature of both melanoma and atypical basal cell carcinoma. Our proposed score improves diagnostic accuracy and confidence. Absence of pigmented features was associated with lower diagnostic accuracy and confidence.
Metabolomics offers a noninvasive methodology to identify metabolic markers for pathogenesis and diagnosis of diseases. This work aimed to characterize circulating metabolic signatures of benign ...thyroid nodule (BTN) and papillary thyroid carcinoma (PTC) via serum‐plasma matched metabolomics. A cohort of 1,540 serum‐plasma matched samples and 114 tissues were obtained from healthy volunteers, BTN and PTC patients enrolled from 6 independent centers. Untargeted metabolomics was determined by liquid chromatography‐quadrupole time‐of‐flight mass spectrometric and multivariate statistical analyses. The use of serum‐plasma matched samples afforded a broad‐scope detection of 1,570 metabolic features. Metabolic phenotypes revealed significant pattern differences for healthy versus BTN and healthy versus PTC. Perturbed metabolic pathways related mainly to amino acid and lipid metabolism. It is worth noting that, BTN and PTC showed no significant differences but rather overlap in circulating metabolic signatures, and this observation was replicated in all study centers. For differential diagnosis of healthy versus thyroid nodules (BTN + PTC), a panel of 6 metabolic markers, namely myo‐inositol, α‐N‐phenylacetyl‐L‐glutamine, proline betaine, L‐glutamic acid, LysoPC(18:0) and LysoPC(18:1) provided area under the curve of 97.68% in the discovery phase and predictive accuracies of 84.78–98.18% in the 4 validation centers. Taken together, serum‐plasma matched metabolomics showed significant differences in circulating metabolites for healthy versus nodules but not for BTN versus PTC. Our results highlight the true metabolic nature of thyroid nodules, and potentially decrease overtreatment that exposes patients to unnecessary risks.
What's new?
When thyroid nodules are classified “indeterminate,” is it better to wait and see, or take out the thyroid? Usually, doctors remove the thyroid, resulting in a lifetime of levothyroxine replacement, yet most often the nodules are not cancerous. Here, the authors investigated whether metabolic profile could give a more accurate prediction of whether a thyroid nodule is cancerous. They tested healthy patients, those with benign nodules, and those with papillary thyroid carcinoma. Healthy patients showed distinct differences from those with benign nodules and those with carcinomas, while significant overlap was observed between circulating metabolites from BTN and PTC patients.
Detecting cancer at an early stage before clinical manifestation could be an effective strategy to decrease cancer mortality. Thus, identifying liquid biopsy biomarkers with high efficacy could be a ...promising approach for non-invasive diagnosis of cancer.
Liquid biopsies are increasingly used as a supplement to biopsy, as it enables disease progression to be detected months before clinical and radiographic confirmation. Many bodily fluids contain exosomal microRNAs (miRNAs) which could provide a new class of biomarkers for early and minimally invasive cancer diagnosis due to the stability of miRNAs in exosomes. In this review, we mainly focused on the exosomal miRNAs (liquid biopsy) as biomarkers in the diagnosis and prognosis of various cancers.
Exosomal miRNAs can be used as diagnostic and prognosis biomarkers that provide unique insights and a more dynamic perspective of the progression and therapeutic responses in various malignancies. Therefore, the development of novel and more sensitive technologies that exploit exosomal miRNAs should be a priority for cancer management.
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•An ultrasensitive fluorescent breath ammonia sensor (BFCUR-ENF) was prepared for noninvasive diagnosis.•BFCUR-ENF showed ultra-low LOD for ammonia and exhibited good photo-stability ...and recyclability.•BFCUR-ENF was used for noninvasive diagnosis of patients with chronic kidney disease (CKD) and Helicobacter pylori (H. pylori) infection.
Breath ammonia detection has been a significant non-invasive approach for disease diagnosis. However, the reported methods for breath ammonia detection suffer from high cost, time-consuming, complex operation, or low selectivity. Fluorescence analysis as an alternative method has not been introduced in the detection of breath ammonia due to its insufficient sensitivity. In this work, a rationally designed strategy is proposed to improve the sensitivity of fluorescence sensors by increasing the amount of recognition site and enhancing the brightness of the solid-state fluorescence in sensor molecule. Briefly, three curcumin (CUR) derivatives BFCUR, MBFCUR and MBFCURM with D-π-A-π-D conjugated system were synthesized. Compared with the other two control molecules MBFCUR and MBFCURM, whose phenol groups at one or both ends of BFCUR were protected by a methyl group, BFCUR has two response sites, thus, two intramolecular charge transfer (ICT) interactions occurred after exposure to ammonia, suggesting the improved sensitivity. Moreover, the large steric hindrance of boron trifluoride in BFCUR can prevent the π-π stacking of molecules and endow BFCUR with bright solid-state fluorescence. BFCUR was subsequently loaded into electrospun nanofibers (ENFs) with high specific surface area, which further improved the detection sensitivity. The obtained BFCUR-loaded ENFs sensor (denoted as BFCUR-ENF) exhibited ultra-low LOD of 22 ppb for ammonia. BFCUR-ENF is successfully applied to breath ammonia detection in healthy volunteers, patients with chronic kidney disease (CKD) and Helicobacter pylori (H. pylori) infection, demonstrating its great application potentials. Taken together, the first fluorescent sensor for breath ammonia detection was successfully constructed for noninvasive diagnosis of CKD and H. pylori.
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