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EClinicalMedicine Aug 2023Anal cancer prevention has two critical points: the incidence rate is several fold higher for some groups, such as people living with human immunodeficiency virus (HIV)...
BACKGROUND
Anal cancer prevention has two critical points: the incidence rate is several fold higher for some groups, such as people living with human immunodeficiency virus (HIV) and men who have sex with men (MSM), and there is not a well-defined guideline for its screening. This systematic review evaluates the accuracy of DNA HRHPV (high-risk human papillomavirus), mRNA HPV, DNA HPV16 isolated and p16 staining biomarkers in anal canal smears for identifying anal intraepithelial neoplasia (AIN) 2 or 3, summarised as anal high-grade squamous intraepithelial lesions (aHSIL), and cancer.
METHODS
We searched the MEDLINE, Cochrane Library and Embase electronic databases as well as Grey literature to identify eligible papers published up to 31st July 2022. This systematic review and meta-analysis included observational studies comparing biomarker tests to histopathology after HRA (High-resolution Anoscopy) as a reference standard. We (ACM, TF) analysed studies in which patients of both sexes were screened for anal cancer using DNA HRHPV, mRNA HPV, DNA HPV16 and/or p16 biomarkers. The analysis was performed in pairs, for instance AIN2 or worse (AIN2+) vs. AIN1, HPV infection and normal (AIN1-). PROSPERO CRD42015024201.
FINDINGS
We included 21 studies with 7445 patients. DNA HR HPV showed a higher sensitivity 92.4% (95% CI 84.2-96.5), specificity 41.7% (95% CI 33.9-44.9) and AUC 0.67, followed by the mRNA HPV test, with a sensitivity 77.3% (95% CI 73.2%-80.9%), specificity 61.9% (95% CI 56.6-66.9) and AUC 0.78. DNA HPV16 showed higher specificity 71.7% (95% CI 55.3-83.8), followed by p16 test, 64.1% (95% CI 51.0-75.4); Sensitivity of DNA HPV16 was 53.3% (95% CI 35.4-70.3) and AUC 0.69, while p16 had a sensitivity of 68.8% (95% CI 47.9-84.1) and AUC 0.74. Subgroup analysis of MSM with HIV, with 13 studies and 5123 patients, showed similar accuracy, with a bit higher sensitivities and lower specificities. Considering the measure of the total between-study variability, mRNA HPV tests showed the smallest area of the 95% prediction ellipse, 6.0%, influenced by the low logit sensitivity, 0.011. All other groups of tests exceed 50% prediction ellipse area, which represent a high heterogeneity.
INTERPRETATION
Our findings suggested that DNA HR HPV can be a useful tool for screening for aHSIL and anal cancer if followed by biomarker with a higher specificity. As an isolated test, mRNA HPV had better performance.
FUNDING
There was no funding source for this study.
PubMed: 37588624
DOI: 10.1016/j.eclinm.2023.102128 -
Journal of Oncology 2019This systematic review evaluates the accuracy of the mRNA HPV biomarker in cervical smears to identify cervical intraepithelial neoplasia (CIN) 2 or 3 and cervical... (Review)
Review
OBJECTIVE
This systematic review evaluates the accuracy of the mRNA HPV biomarker in cervical smears to identify cervical intraepithelial neoplasia (CIN) 2 or 3 and cervical cancer.
DATA SOURCE
Eligible studies were identified by performing a search of electronic databases on Medline via Pubmed, Lilacs, Cochrane Library, Embase, and Grey literature for papers published between January 1990 and June 2018.
STUDY ELIGIBILITY CRITERIA
As no randomized studies were identified, this review focuses on observational studies in which the mRNA HPV diagnostic test was compared to a histopathology reference standard. We analyzed studies that included women screened for cervical cancer using mRNA HPV.
STUDY APPRAISAL AND SYNTHESIS METHODS
After screening, 61 studies including 29,674 patients met the inclusion criteria and were analyzed. Dichotomization was performed by defining CIN2 or worse (CIN2+) versus CIN1, HPV infection, and normal (CIN 1-). The analysis was discriminated by the following tests: Aptima, PreTect HPV Profeer, NucliSens EasyQ HPV, OncoTect, and Quantivirus.
RESULTS
Analyzing by technique, Aptima, with 28 studies, exhibited superior performance, showing for the outcomes CIN2+ and CIN3+ an AUC of 0.88 (0.82-0.95) and 0.91 (0.84-0.99), a pooled sensitivity of 92.8% (95%CI 91.9-93.7) and 95.6% (95%CI 94.5-96.5), and a pooled specificity of 60.5% (95%CI 59.8-61.3) and 61.9% (95%CI 61.1-62.7), respectively.
CONCLUSION
This study supports the current hypothesis that the mRNA HPV assay is an adequate tool for secondary cervical cancer screening.
PubMed: 31281360
DOI: 10.1155/2019/6935030 -
Biomarkers in Medicine Apr 2019This systematic review evaluates the accuracy of mRNA HPV biomarker for the identification of cervical intra-epithelial neoplasia (CIN) or cervical cancer during a... (Meta-Analysis)
Meta-Analysis
This systematic review evaluates the accuracy of mRNA HPV biomarker for the identification of cervical intra-epithelial neoplasia (CIN) or cervical cancer during a follow-up after conization, taking histopathology as reference standard. A search of electronic databases was performed, for studies published until June 2018. As results, after screening, five studies including 1148 patients met the inclusion criteria. Dichotomization was performed by CIN2+ versus CIN1-. By analyzing all five studies, a sensitivity of 62.4% (95% CI: 54.8-69.7), specificity of 91.9% (95% CI: 90.0-93.5) and area under the curve of 0.5685 were revealed. mRNA HPV assay presents a high specificity and is an adequate tool for cervical cancer screening in the follow-up after conization.
Topics: Alphapapillomavirus; Female; Humans; RNA, Messenger; Recurrence; Sensitivity and Specificity; Uterine Cervical Neoplasms
PubMed: 30924676
DOI: 10.2217/bmm-2018-0373 -
Journal of Cancer Research and Clinical... Dec 2023During eukaryotic gene expression, alternative splicing of messenger RNA precursors is critical in increasing protein diversity and regulatory complexity. Multiple... (Review)
Review
During eukaryotic gene expression, alternative splicing of messenger RNA precursors is critical in increasing protein diversity and regulatory complexity. Multiple transcript isoforms could be produced by alternative splicing from a single gene; they could eventually be translated into protein isoforms with deleted, added, or altered domains or produce transcripts containing premature termination codons that could be targeted by nonsense-mediated mRNA decay. Alternative splicing can generate proteins with similar, different, or even opposite functions. Increasingly strong evidence indicates that abnormal RNA splicing is a prevalent and crucial occurrence in cellular differentiation, tissue advancement, and the development and progression of cancer. Aberrant alternative splicing could affect cancer cell activities such as growth, apoptosis, invasiveness, drug resistance, angiogenesis, and metabolism. This systematic review provides a comprehensive overview of the impact of abnormal RNA alternative splicing on the development and progression of hepatocellular carcinoma.
Topics: Humans; Alternative Splicing; RNA; Carcinoma, Hepatocellular; RNA, Messenger; Liver Neoplasms; Protein Isoforms; RNA Splicing
PubMed: 37898981
DOI: 10.1007/s00432-023-05474-8 -
Carcinogenesis Feb 2024Solute carrier organic anion (SLCO) transporters (OATP transporters) are involved in cellular uptake of drugs and hormones. Germline variants in SLCO1B3 and SLCO2B1 have... (Meta-Analysis)
Meta-Analysis
Solute carrier organic anion (SLCO) transporters (OATP transporters) are involved in cellular uptake of drugs and hormones. Germline variants in SLCO1B3 and SLCO2B1 have been implicated in prostate cancer progression and therapy response, including to androgen deprivation and statin medications, but results have appeared heterogeneous. We conducted a cohort study of five single-nucleotide polymorphisms (SNPs) in SLCO1B3 and SLCO2B1 with prior evidence among 3208 men with prostate cancer who participated in the Health Professionals Follow-up Study or the Physicians' Health Study, following participants prospectively after diagnosis over 32 years (median, 14 years) for development of metastases and cancer-specific death (lethal disease, 382 events). Results were suggestive of, but not conclusive for, associations between some SNPs and lethal disease and differences by androgen deprivation and statin use. All candidate SNPs were associated with SLCO mRNA expression in tumor-adjacent prostate tissue. We also conducted a systematic review and harmonized estimates for a dose-response meta-analysis of all available data, including 9 further studies, for a total of 5598 patients and 1473 clinical events. The A allele of the exonic SNP rs12422149 (14% prevalence), which leads to lower cellular testosterone precursor uptake via SLCO2B1, was associated with lower rates of prostate cancer progression (hazard ratio per A allele, 0.80; 95% confidence interval, 0.69-0.93), with little heterogeneity between studies (I2, 0.27). Collectively, the totality of evidence suggests a strong association between inherited genetic variation in SLCO2B1 and prostate cancer prognosis, with potential clinical use in risk stratification related to androgen deprivation therapy.
Topics: Male; Humans; Prostatic Neoplasms; Androgen Antagonists; Androgens; Follow-Up Studies; Cohort Studies; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Prospective Studies; Genotype; Organic Anion Transporters; Solute Carrier Organic Anion Transporter Family Member 1B3
PubMed: 37856781
DOI: 10.1093/carcin/bgad075 -
Danish Medical Journal Mar 2016The study of potential biomarkers in haematological malignancies has gained momentum in past decades. We compiled a systematic review to outline potential biomarkers... (Review)
Review
INTRODUCTION
The study of potential biomarkers in haematological malignancies has gained momentum in past decades. We compiled a systematic review to outline potential biomarkers based on alternative pre-mRNA splicing that were suggested to be clinically useful for the diagnosis, prognosis and response to therapeutics in diffuse large B-cell lymphoma (DLBCL).
METHODS
A comprehensive search of the literature in PubMed, Embase and Scopus was performed and supplemented with screening of reference lists. Only articles concerning potential biomarkers originating from reports on alternative pre-mRNA splicing were included. The contributions of these studies will help develop personalised medicine. Therefore, the clinical utility of the potential biomarkers was evaluated.
RESULTS
A total of 16 studies were included of which eight described seven different potential diagnostic biomarkers. Eight studies reported two potential prognostic biomarkers for CD44, its spliced mRNA variants and the resulting proteins that were the most frequently reported. Furthermore, two studies reported two proteins originating from alternative pre-mRNA splicing as potentially predictive biomarkers.
CONCLUSIONS
Alternative pre-mRNA splicing is a promising potential diagnostic, prognostic and predictive biomarker for the identification of pathogenic impacts in DLBCL. The use of these potential biomarkers in the clinical management of DLBCL awaits prospective clinical validation supporting its potential to contribute to the shift towards more personalised medicine.
Topics: Biomarkers, Tumor; Disease Management; Humans; Lymphoma, Large B-Cell, Diffuse; Prognosis; RNA Precursors
PubMed: 26931194
DOI: No ID Found -
Alimentary Pharmacology & Therapeutics May 2024The faecal immunochemical test (FIT) is an inexpensive and convenient modality to screen for colorectal cancer. However, its one-time sensitivity for detecting... (Review)
Review
BACKGROUND
The faecal immunochemical test (FIT) is an inexpensive and convenient modality to screen for colorectal cancer. However, its one-time sensitivity for detecting colorectal cancer and cancer precursors is limited. There is growing interest in using the non-haemoglobin contents of FIT residual buffer to enhance colonic neoplasia detection.
AIM
To establish from the literature a framework to catalogue candidate biomarkers within FIT residual buffer for non-invasive colorectal cancer screening.
METHODS
The search strategy evaluated PubMed, Scopus, Web of Science, Embase, and Google Scholar for publications through 25 October 2023, with search terms including FIT, buffer, OC-sensor, biomarkers, microbiome, microRNA (miR), colon, rectum, screening, neoplasm, and early detection. Studies employing home-based collection samples using quantitative FIT first processed for haemoglobin were included. One author reviewed all articles; a second author completed a 20% full-text audit to ensure adherence to eligibility criteria.
RESULTS
A broad search yielded 1669 studies and application of eligibility criteria identified 18 relevant studies. Multiple protein, DNA/RNA, and microbiome biomarkers (notably haptoglobin, miR-16, miR-27a-3p, miR-92a, miR-148a-3p, miR-223, miR-421, let-7b-5p, and Tyzzerella 4) were associated with colorectal neoplasia. Furthermore, studies highlighted the short-term stability of biomarkers for clinical use and long-term stability for research purposes.
CONCLUSIONS
This scoping review summarises the framework and progress of research on stability of biomarkers in FIT residual buffer and their associations with colorectal neoplasia to guide opportunities for further confirmatory studies to enhance colorectal cancer screening.
Topics: Humans; Early Detection of Cancer; Colorectal Neoplasms; Rectum; MicroRNAs; Hemoglobins; Occult Blood; Biomarkers; Feces; Mass Screening
PubMed: 38534182
DOI: 10.1111/apt.17947 -
Blood Cancer Journal Jun 2020B-cell maturation antigen (BCMA) plays a critical role in regulating B-cell proliferation and survival. There is evidence for BCMA expression in various hematologic... (Meta-Analysis)
Meta-Analysis
B-cell maturation antigen (BCMA) plays a critical role in regulating B-cell proliferation and survival. There is evidence for BCMA expression in various hematologic malignancies, suggesting that BCMA may play an important role as a biomarker or therapeutic target in these diseases. Given advances in understanding the role of BCMA in B-cell development and the promise of BCMA as a therapeutic target, a systematic review is needed to rigorously assess the evidence for BCMA expression and identify areas of consensus and future research. The objective of this review was to summarize the evidence on BCMA protein and mRNA expression across hematologic malignancies. Using a PubMed database search up to 28 August 2019, a systematic literature review of publications reporting BCMA expression in patients with hematologic malignancies was conducted. Data from published congress abstracts presented at the American Society of Clinical Oncology and the American Society of Hematology were also searched. Studies that assessed BCMA expression (protein or mRNA) in patients of any age with hematologic malignancies were included. A total of 21 studies met inclusion criteria and were included in the review. BCMA was expressed in several hematologic malignancies, including multiple myeloma (MM), chronic lymphocytic leukemia, acute B-lymphoblastic leukemia, non-Hodgkin lymphoma (NHL), and Hodgkin lymphoma. BCMA was expressed at uniformly high levels across all 13 MM studies and at low to moderate levels in acute myeloid leukemia and acute lymphoblastic leukemia. These results suggest that BCMA is a relevant target in MM as well as in a subset of B-cell leukemia. BCMA expression in Hodgkin lymphoma and NHL varied across studies, and further research is needed to determine the utility of BCMA as an antibody target and biomarker in these diseases. Differences in sample type, timing of sample collection, and laboratory technique used may have affected the reporting of BCMA levels.
Topics: B-Cell Maturation Antigen; Gene Expression Regulation, Neoplastic; Hematologic Neoplasms; Hodgkin Disease; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin; Multiple Myeloma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; RNA, Messenger
PubMed: 32606424
DOI: 10.1038/s41408-020-0337-y -
Clinical and Translational... Jun 2016Despite moderate to high detection rates of fecal immunochemical tests (FITs) of colorectal cancer (CRC), detection of adenomas remains limited. Further stool tests... (Review)
Review
OBJECTIVES
Despite moderate to high detection rates of fecal immunochemical tests (FITs) of colorectal cancer (CRC), detection of adenomas remains limited. Further stool tests exist, which are not used in routine practice, such as DNA or RNA markers and protein markers. We aimed at systematically investigating and summarizing evidence for diagnostic performance of combinations of FIT with other stool tests compared with FIT alone in early detection of CRC and its precursors.
METHODS
We systematically reviewed studies that evaluated FITs in combination with other stool tests and compared measures of diagnostic accuracy with and without additional stool tests. PubMed and Web of Science were searched from inception to May 2015. Reference lists of eligible studies were also screened. Two reviewers extracted data independently.
RESULTS
Some of the reports on DNA, RNA, or tissue tests, including tests based on DNA mutations, methylation, and integrity in selected genes as well as microRNA expression, showed some improvements of diagnostic test accuracy. In contrast, so far assessed stool protein markers did generally not lead to substantial improvements in performance of FIT when added to the latter. Many marker combinations were reported only in one study each, and few studies were conducted in a true screening setting.
CONCLUSIONS
Several stool markers show potential to improve performance of FITs. However, the results require confirmation in further studies, which should also evaluate the costs and cost-effectiveness of combined screening strategies.
PubMed: 27253514
DOI: 10.1038/ctg.2016.29 -
Cancer Epidemiology, Biomarkers &... Oct 2007Despite different available methods for colorectal cancer (CRC) screening and their proven benefits, morbidity, and mortality of this malignancy are still high, partly... (Review)
Review
BACKGROUND
Despite different available methods for colorectal cancer (CRC) screening and their proven benefits, morbidity, and mortality of this malignancy are still high, partly due to low compliance with screening. Minimally invasive tests based on the analysis of blood specimens may overcome this problem. The purpose of this review was to give an overview of published studies on blood markers aimed at the early detection of CRC and to summarize their performance characteristics.
METHOD
The PUBMED database was searched for relevant studies published until June 2006. Only studies with more than 20 cases and more than 20 controls were included. Information on the markers under study, on the underlying study populations, and on performance characteristics was extracted. Special attention was given to performance characteristics by tumor stage.
RESULTS
Overall, 93 studies evaluating 70 different markers were included. Most studies were done on protein markers, but DNA markers and RNA markers were also investigated. Performance characteristics varied widely between different markers, but also between different studies using the same marker. Promising results were reported for some novel assays, e.g., assays based on SELDI-TOF MS or MALDI-TOF MS, for some proteins (e.g., soluble CD26 and bone sialoprotein) and also for some genetic assays (e.g., L6 mRNA), but evidence thus far is restricted to single studies with limited sample size and without further external validation.
CONCLUSIONS
Larger prospective studies using study populations representing a screening population are needed to verify promising results. In addition, future studies should pay increased attention to the potential of detecting precursor lesions.
Topics: Biomarkers, Tumor; Genetic Markers; Humans; Neoplasm Proteins; Neoplasm Staging; Neoplasms; Predictive Value of Tests
PubMed: 17932341
DOI: 10.1158/1055-9965.EPI-06-0994