Tests For Detection Of Cancer Research Articles

A non-invasive screening method using Caenorhabditis elegans for early detection of multiple cancer types: A prospective clinical study

Cancer is the second leading cause of death worldwide, according to the World Health Organization, surpassed only by cardiovascular diseases. Early identification and intervention can significantly improve outcomes. However, finding a universal, non-invasive, economical, and precise method for early cancer detection remains a significant challenge. This study explores the efficacy of an innovative cancer detection test, N-NOSE, leveraging a Caenorhabditis elegans olfactory assay on urine samples across a diverse patient group exceeding 1600 individuals diagnosed with various cancers, with samples from the Shikoku Cancer Center (Ehime, Japan) under approved ethical standards. Current cancer screening techniques often require invasive procedures, can be painful or complex, with poor performance, and might be prohibitively costly, limiting accessibility for many. N-NOSE addresses these challenges head-on by offering a test based on urine analysis, eliminating the need for invasive methods, and being more affordable with higher performance at early stages than extensive blood tests or comprehensive body scans for cancer detection. In this study, N-NOSE demonstrated a capability to accurately identify upwards of 20 cancer types, achieving detection sensitivities between 60 and 90 %, including initial-stage cancers. The findings robustly advocate for N-NOSE's potential as a revolutionary, cost-effective, and minimally invasive strategy for broad-spectrum early cancer detection. It is also particularly significant in low- and middle-income countries with limited access to advanced cancer diagnostic methods, which may contribute to the improved outcome of affected individuals.

Analytical Validation of the Multitarget Stool RNA Test for Colorectal Cancer Screening.

The multitarget stool RNA (mt-sRNA) test (ColoSense) is a noninvasive diagnostic test that screens for colorectal cancer and advanced adenomas in average-risk individuals aged 45 years and older. The mt-sRNA test incorporates a commercially available fecal immunochemical test, concentration of eight RNA transcripts, and participant-reported smoking status. As part of the CRC-PREVENT (Colorectal Cancer and Pre-Cancerous Adenoma Non-Invasive Detection Test) clinical trial, 12 analytical validation studies were conducted to assess analytical sensitivity, linearity, precision, interfering substances, cross-reactivity, carry-over, cross-contamination, and robustness. Analytical validation of the mt-sRNA test demonstrated limit of blank, limit of detection, and limit of quantification of <0.6, <0.7, and ≤2.5 copies/μL for all markers, respectively. The mt-sRNA test demonstrated linearity between 2.5 and 2500 copies/μL, and <20% coefficient of variation, and/or ≥95% concordance with regard to precision, interfering substances, carry-over, cross-contamination, and robustness. There was no significant impact of cross-reactivity from non-colorectal cancer diseases. These data provide a framework for laboratories to complete analytical validation for RNA-based panels that require premarket approval as a class III medical device from the US Food and Drug Administration.

Clinical validation of a cell-free DNA fragmentome assay for augmentation of lung cancer early detection.

Lung cancer screening via annual low-dose computed tomography (LDCT) has poor adoption. We conducted a prospective case-control study among 958 individuals eligible for lung cancer screening to develop a blood-based lung cancer detection test that when positive is followed by an LDCT. Changes in genome-wide cell-free DNA (cfDNA) fragmentation profiles (fragmentomes) in peripheral blood reflected genomic and chromatin characteristics of lung cancer. We applied machine learning to fragmentome features to identify individuals who were more or less likely to have lung cancer. We trained the classifier using 576 cases and controls from study samples, and then validated it in a held-out group of 382 cases and controls. The validation demonstrated high sensitivity for lung cancer, and consistency across demographic groups and comorbid conditions. Applying test performance to the screening eligible population in a five-year model with modest utilization assumptions suggested the potential to prevent thousands of lung cancer deaths.

Micro tensile tester measurement of biomechanical properties and adhesion force of microtubule-polymerization-inhibited cancer cells

Both mechanical and adhesion properties of cancer cells are complex and reciprocally related to migration, invasion, and metastasis with large cell deformation. Therefore, we evaluated these properties for human cervical cancer cells (HeLa) simultaneously using our previously developed micro tensile tester system. For efficient evaluation, we developed image analysis software to modify the system. The software can analyze the tensile force in real time. The modified system can evaluate the tensile stiffness of cells to which a large deformation is applied, also evaluate the adhesion strength of cancer cells that adhered to a culture substrate and were cultured for several days with their adhesion maturation. We used the modified system to simultaneously evaluate the stiffness of the cancer cells to which a large deformation was applied and their adhesion strength. The obtained results revealed that the middle phase of tensile stiffness and adhesion force of the microtubule-depolymerized group treated with colchicine (an anti-cancer drug) (stiffness, 13.4 ± 7.5 nN/%; adhesion force, 460.6 ± 258.2 nN) were over two times larger than those of the control group (stiffness, 5.0 ± 3.5 nN/%; adhesion force, 168.2 ± 98.0 nN). Additionally, the same trend was confirmed with the detailed evaluation of cell surface stiffness using an atomic force microscope. Confocal fluorescence microscope observations showed that the stress fibers (SFs) of colchicine-treated cells were aligned in the same direction, and focal adhesions (FAs) of the cells developed around both ends of the SFs and aligned parallel to the developed direction of the SFs. There was a possibility that the microtubule depolymerization by the colchicine treatment induced the development of SFs and FAs and subsequently caused an increment of cell stiffness and adhesion force. From the above results, we concluded the modified system would be applicable to cancer detection and anti-cancer drug efficacy tests.

Discovery and technical validation of high-performance methylated DNA markers for the detection of cervical lesions at risk of malignant progression in low- and middle-income countries

BackgroundCervical cancer remains a leading cause of death, particularly in developing countries. WHO screening guidelines recommend human papilloma virus (HPV) detection as a means to identify women at risk of developing cervical cancer. While HPV testing identifies those at risk, it does not specifically distinguish individuals with neoplasia. We investigated whether a quantitative molecular test that measures methylated DNA markers could identify high-risk lesions in the cervix with accuracy.ResultsMarker discovery was performed in TCGA-CESC Infinium Methylation 450 K Array database and verified in three other public datasets. The panel was technically validated using Quantitative Multiplex-Methylation-Specific PCR in tissue sections (N = 252) and cervical smears (N = 244) from the USA, South Africa, and Vietnam. The gene panel consisted of FMN2, EDNRB, ZNF671, TBXT, and MOS. Cervical tissue samples from all three countries showed highly significant differential methylation in squamous cell carcinoma (SCC) with a sensitivity of 100% [95% CI 74.12–100.00], and specificity of 91% [95% CI 62.26–99.53] to 96% [95% CI 79.01–99.78], and receiver operating characteristic area under the curve (ROC AUC) = 1.000 [95% CI 1.00–1.00] compared to benign cervical tissue, and cervical intraepithelial neoplasia 2/3 with sensitivity of 55% [95% CI 37.77–70.84] to 89% [95% CI 67.20–98.03], specificity of 93% [95% CI 84.07–97.38] to 96% [95% CI 79.01–99.78], and a ROC AUC ranging from 0.793 [95% CI 0.68–0.89] to 0.99 [95% CI 0.97–1.00] compared to CIN1. In cervical smears, the marker panel detected SCC with a sensitivity of 87% [95% CI 77.45–92.69], specificity 95% [95% CI 88.64–98.18], and ROC AUC = 0.925 [95% CI 0.878–0.974] compared to normal, and high-grade squamous intraepithelial lesion (HSIL) at a sensitivity of 70% (95% CI 58.11–80.44), specificity of 94% (95% CI 88.30–97.40), and ROC AUC = 0.884 (95% CI 0.822–0.945) compared to low-grade intraepithelial lesion (LSIL)/normal in an analysis of pooled data from the three countries. Similar to HPV-positive, HPV-negative cervical carcinomas were frequently hypermethylated for these markers.ConclusionsThis 5-marker panel detected SCC and HSIL in cervical smears with a high level of sensitivity and specificity. Molecular tests with the ability to rapidly detect high-risk HSIL will lead to timely treatment for those in need and prevent unnecessary procedures in women with low-risk lesions throughout the world. Validation of these markers in prospectively collected cervical smear cells followed by the development of a hypermethylated marker-based cervical cancer detection test is warranted.

Barriers to the use of tests for early detection of colorectal cancer in Chile

This study aimed to assess the use of colorectal cancer (CRC) tests for prevention and early detection, alongside exploring the associated barriers to these tests. A stratified national survey was conducted in Chile, involving 1893 respondents (with a 2.3% error margin and 95% confidence interval). Logistic and multinomial regression analyses were employed to examine variations in test utilization likelihood and barrier. We found that the key determinants for undergoing CRC tests included age, health status, possession of private health insurance, and attainment of postgraduate education. Notably, 18% and 29% of respondents covered by public and private insurance, respectively, cited personal prevention as the primary motivation for test uptake. The principal obstacle identified was lack of knowledge, mentioned by 65% of respondents, while 29% and 19% of the publicly and privately insured respectively highlighted lack of access as a barrier. The results of this study provide valuable insights into factors influencing CRC screening, aiming to inform public health policies for expanding national coverage beyond diagnosis and treatment to encompass preventive measures.

Qualitative Fecal Immunochemical Test as a Screening Test for Colorectal Cancer

Colorectal cancer is one of the most common cancers, causing mortality, morbidity, and economic burden. Patient survival differs due to differences in access to health facilities, as well as diagnostic and therapeutic modalities. Early detection can allow colorectal cancer to be diagnosed at an earlier stage, improving patient outcomes and lowering mortality. Due to the lack of a national screening program in Indonesia, as well as the uneven availability of colonoscopy tools, the fecal immunochemical test has become the preferred screening method. This cross-sectional study aims to validate the application of the fecal immunochemical test for colorectal cancer detection. Fecal immunochemical test examination is performed on all patients with suspected colorectal cancer who will undergo a colonoscopy examination at Prof. Hospital dr. I.G.N.G. Ngoerah, Bali, Indonesia. Histopathological examination is used to diagnose colorectal cancer. This study included 78 people with a colorectal cancer prevalence of 40.91%. There were 38(57.6%) subjects with positive fecal immunochemical test results in this study, and 25(65.6%) of them were diagnosed with colorectal cancer. The sensitivity, specificity, positive predictive value, and negative predictive value of the qualitative fecal immunochemical test in detecting colorectal cancer were 92.59%, 66.67%, 65.79%, and 92.86%, respectively. The qualitative fecal immunochemical test has high sensitivity and can be used as an objective and accurate method of screening symptomatic patients with suspected CRC for colonoscopy.

Prostate Cancer Screening Behaviors and Health Beliefs Regarding Prostate Cancer Screening of Individuals Over 50 Years of Age: A Descriptive, Cross-Sectional Study

Purpose: This descriptive cross-sectional study was conducted to assess the prostate cancer screening behaviors and health beliefs related to prostate cancer screening among individuals aged 50 and over. &#x0D; Material and Methods: The study sample consisted of 72 men aged 50 and over receiving treatment at the orthopedics and traumatology clinic of a university hospital. Data were collected using a "Personal Information Form" and the "Prostate Cancer Screening Health Belief Model Scale." &#x0D; Results: The mean age of the participants in the study was 61.59±8.51 years. It was found that 22.2% of the participants had undergone Prostate-Specific Antigen testing, 73.6% had no knowledge about prostate cancer, and 75% had no knowledge about early detection tests for prostate cancer. Furthermore, participants who had knowledge about prostate cancer and early detection, had a family history of prostate cancer, and considered undergoing prostate examination had a higher rate of undergoing Prostate-Specific Antigen testing. Those who had never undergone a prostate examination, had no knowledge about prostate cancer and early detection tests, and did not plan to undergo prostate examination within the next six months had higher scores on the barrier perception scale, while those who had undergone Prostate-Specific Antigen testing and planned to undergo prostate examination within the next six months had higher scores on the health motivation perception scale. &#x0D; Conclusion: The study revealed a low rate of Prostate-Specific Antigen testing for early detection of prostate cancer, and participants' knowledge and health beliefs and perceptions related to prostate cancer and early detection tests were identified as key factors influencing prostate cancer screening behaviors.

Abstract 6091: Multi-cancer early cancer detection and cancer-type identification with high sensitivity non-invasive using urine: Pancreatic lung cancer early detection

Abstract N-NOSE, a breakthrough cancer detection test from HIROTSU BIO SCIENCE, utilizes the unique chemotactic behavior of the nematode C. elegans. This nematode is drawn to the urine of individuals with 15 different types of cancers (including stomach, colon-rectum, lung, breast, pancreas, liver, prostate, uterus, esophagus, gallbladder, bile duct, kidney, urinary bladder, ovary, oropharynx) while avoiding urine from healthy persons, making N-NOSE a comprehensive primary screening tool. It has a high accuracy rate, with 87.5% sensitivity and 90.2% specificity for early-stage cancers. Being non-invasive and reasonably priced, N-NOSE has been a significant success in Japan since its 2020 launch, with over 500,000 screenings.This presentation delves into the technology aspect of N-NOSE in Japan, comparing its clinical research and key findings with competitors to underscore its effectiveness in early cancer detection. Furthermore, N-NOSE now advances to not only detect cancer but also identify its type in a noninvasive way, using urine and with high PPV.With pancreatic cancer being particularly lethal, we outline “N-NOSE plus pancreas,” the world’s first pancreatic cancer detection test at an early stage. This involves genetically modifying C. elegans to react specifically to early-stage pancreatic cancer urine samples, a development centered on the newly identified cr-4 GPCR in AWC neurons. Next, we profile our newest liver-cancer-specific test, “N-NOSE plus liver,” which offers early liver cancer detection with high sensitivity and specificity using urine.Finally, we highlight how N-NOSE bridges the gap in cancer screening and type identification, offering a complete, non-invasive solution. Citation Format: Eric Di Luccio, Takaaki Hirotsu. Multi-cancer early cancer detection and cancer-type identification with high sensitivity non-invasive using urine: Pancreatic lung cancer early detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6091.

Noninvasive Tests for Bladder Cancer Detection and Surveillance: A Systematic Review of Commercially Available Assays.

An important reason for the high health care costs associated with bladder cancer is the need for frequent cystoscopy for detection and surveillance of this disease. Cytologic analysis of voided urine specimens can assist, but is too inaccurate to replace cystoscopy. In an effort to create reliable, objective, noninvasive mechanisms for detecting bladder cancer, a number of urine-based molecular tests have been developed with the ultimate goal of reducing the frequency of cystoscopy. To summarize the performance of urine-based biomarker tests, currently commercially available in the US, as part of the initial workup for hematuria and for bladder cancer surveillance. In accordance with PRISMA guidelines we performed a systematic review of the literature on the performance of NMP22, BTA, UroVysion, ImmunoCyt/uCyt, CxBladder, and Bladder EpiCheck. Median sensitivity, specificity, negative (NPV) and positive predictive values (PPV) were calculated for each test based on the included studies. Twenty-eight studies met inclusion criteria for the performance of five urine-based biomarker tests in the setting hematuria workup. Median sensitivity ranged from 65.7% -100% and specificity ranged from 62.5% -93.8%. Median NPV ranged from 94.2% -98.3% and PPV ranged from 29% -58.7%. Fourteen studies met inclusion criteria for the performance of six tests in the setting of bladder cancer surveillance. Median sensitivity ranged from 22.6% -92.0% and specificity from 20.5% -97.9%. Median NPV ranged from 52.9% -96.5% and PPV ranged from 48.1% -75.7%. Our analysis finds that while these tests may provide some clinical utility, none of the assays have thus far demonstrated objective evidence to supplant the gold diagnostic standard.

Next-Generation Screening for Colorectal Cancer, an Incremental Approach to a Global Disease.

New screening tests for early detection of colorectal cancer and its precursors are rapidly emerging with the focus on noninvasive tests which can be used in both structured opportunistic and population-based organized screening programs. Novel technologies are identifying new combinations of promising markers. Conducting large prospective clinical trials of efficacy requires very large numbers of subjects constituting intended-use populations. These trials are often preceded by studies using smaller numbers of "convenience" samples to derive panels of relevant markers and algorithms to combine them and define what constitutes a positive test. The article by Gagrat and colleagues in this issue reports results from one such study designed to yield a "next-generation" multitargeted (mt-sDNA) stool test. This report exemplifies the advantages and limitations of this approach. See related article by Gagrat et al., p. 119.

Abstract IA007: The WID-qEC test for simple and accurate endometrial cancer detection

Abstract Endometrial cancer incidence has been rising over the past ten years. Delays in diagnosis reduce survival and necessitate more aggressive treatment. We developed the WID-qEC test, a PCR-based test that evaluates DNA methylation in gene regions of GYPC and ZSCAN12, using 726 cervico-vaginal samples from women with and without endometrial cancer. So far, the WID-qEC test has been validated in an additional 1388 women in various settings, including a case/control study utilizing self-samples and a nested case/control set from a screening cohort including samples taken up to 3 years prior to endometrial cancer diagnosis. In a recent prospective observational study (the EPI-SURE study), the primary aim was to compare the performance of conventional index imaging tests (i.e., sonography) with the WID-qEC test for endometrial cancer detection. We invited all women aged ≥ 45 years with abnormal uterine bleeding attending a tertiary gynecological diagnostic referral center in the UK between June and November 2022 to participate. A cervicovaginal sample for the WID-qEC test was obtained prior to the current diagnostic pathway, and the test was performed blinded to the clinical outcome. Patients were followed until diagnostic resolution or until June 12, 2023. Four hundred of the eligible 474 women consented to study participation; one patient withdrew. Based on 603 index imaging tests (i.e., sonography), 186 (46.6%) women were recommended for a reference histology test (i.e., biopsy+/-hysteroscopy). Twelve cancers were diagnosed. 198 reference histology test procedures detected nine cancers and missed two; one further cancer was directly diagnosed at hysterectomy without a prior reference test. Endometrial thickness assessment from an ultrasound scan was possible in 379 (95.0%) of the 399 women and a pre-specified cut-off of ≥ 4.5mm had sensitivity, specificity, positive (PPV) and negative (NPV) predictive values of 90.9% (95% CI: 62.3-98.4), 79.1% (95% CI: 74.5-82.9), 11.8% (95% CI: 6.5-20.3) and 99.6% (95% CI: 98.0-99.9), respectively. Using a cut-off of &amp;gt; 3mm, the specificity was 45.8% (95% CI: 40.7–51.0) without a change in sensitivity. The WID-qEC test was possible in 390 (97.7%) of the 399 patients with 90.9% sensitivity (95% CI: 62.3-98.4), 92.1% specificity (95% CI: 88.9-94.4), a PPV of 25.6% (95% CI:14.6-41.1) and a NPV of 99.7% (95% CI: 98.3-99.9) when the pre-specified threshold (WID-qEC sumPMR ≥ 0.03) was applied. When a higher threshold was applied (WID-qEC sumPMR ≥ 0.3) the specificity increased to 97.3% (95% CI: 95.1-98.5) without a change in sensitivity. The WID-qEC test delivers fast results and shows improved performance compared with a combination of imaging index tests. Triage of women with abnormal uterine bleeding using the WID-qEC test could reduce the number of women requiring histological assessments for identification of potential malignancy and, specifically, reduce the false positive rate by up to 95% (from 52.6% based on the endometrial thickness of &amp;gt; 3mm to 2.6% based on a WID-qEC sumPMR ≥ 0.3). Citation Format: Martin Widschwendter, Iona Evans, Daniel Reisel, Allison Jones, Alba Bajrami, Simrit Nijjar, Sarah A Solangon, Rupali Arora, Elisa Redl, Lena Schreiberhuber, Isma Ishaq-Parveen, Julia Rothärmel, Chiara Herzog, Davor Jurkovic. The WID-qEC test for simple and accurate endometrial cancer detection [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr IA007.

Protocol for the ONLOOP trial: pragmatic randomized trial evaluating a province-wide system of personalized reminders for evidence-based surveillance tests in adult survivors of childhood cancer in Ontario

BackgroundChildhood cancer treatment while often curative, leads to elevated risks of morbidity and mortality. Survivors require lifelong periodic surveillance for late effects of treatment, yet adherence to guideline-recommended tests is suboptimal. We created ONLOOP to provide adult survivors of childhood cancer with detailed health information, including summaries of their childhood cancer treatment and recommended surveillance tests for early detection of cardiomyopathy, breast cancer, and/or colorectal cancer, with personalized reminders over time.MethodsThis is an individually randomized, registry-based pragmatic trial with an embedded process and economic evaluation to understand ONLOOP’s impact and whether it can be readily implemented at scale. All adult survivors of childhood cancer in Ontario overdue for guideline-recommended tests will be randomly assigned to one of two arms: (1) intervention or (2) delayed intervention. A letter of information and invitation will detail the ONLOOP program. Those who sign up will receive a personalized toolkit and a screening reminder 6 months later. With the participants’ consent, ONLOOP will also send their primary care clinician a letter detailing the recommended tests and a reminder 6 months later.The primary outcome will be the proportion of survivors who complete one or more of the guideline-recommended cardiac, breast, or colon surveillance tests during the 12 months after randomization. Data will be obtained from administrative databases. The intent-to-treat principle will be followed. Based on our analyses of administrative data, we anticipate allocating at least 862 individuals to each trial arm, providing 90% power to detect an absolute increase of 6% in targeted surveillance tests completed. We will interview childhood cancer survivors and family physicians in an embedded process evaluation to examine why and how ONLOOP achieved success or failed. A cost-effectiveness evaluation will be performed.DiscussionThe results of this study will determine if ONLOOP is effective at helping adult survivors of childhood cancer complete their recommended surveillance tests. This study will also inform ongoing provincial programs for this high-risk population.Trial registrationClinicalTrials.gov NCT05832138.

Novel proteomics-based plasma test for early detection of multiple cancers in the general population

ObjectiveEarly detection of cancer is crucial for reducing the global burden of cancer, but effective screening tests for many cancers do not exist. This study aimed to develop a novel...

Comparing P53 expression and genome-wide transcriptome profiling to Comet assay in lymphocytes from melanoma patients and healthy controls.

This study compared the expression of TP53 in lymphocytes from malignant melanoma (MM) patients with positive sentinel nodes to healthy controls (HCs) following exposure to various doses of UVA radiation. The Lymphocyte Genome Sensitivity (LGS) assay indicated significant differences in DNA damage in lymphocytes between MM patients and HCs. qPCR data demonstrated an overall 3.4-fold increase in TP53 expression in lymphocytes from MM patients compared to healthy controls, following treatment with 0.5 mW/cm2 UVA radiation. Western blotting confirmed that p53 expression was increased in MM lymphocytes following UVA exposure compared to healthy individuals. Genome transcriptome profiling data displayed differences in gene expression between UVA-treated lymphocytes from MM patients and HCs. Peripheral lymphocytes from MM patients are more susceptible to the genotoxic effects of UVA compared to healthy individuals. Our previous studies showed that UVA exposure of various intensities caused significant differences in the levels of DNA damage between lymphocytes from cancer patients compared to HCs through the LGS assay. The present study's results provide further credibility to the LGS assay as a screening test for cancer detection. Peripheral lymphocytes could be a promising blood biopsy biomarker for staging of carcinomas and prevention of carcinoma progression at early stages.

DNA Methylation Testing for Endometrial Cancer Detection in Urine, Cervicovaginal Self-Samples and Cervical Scrapes

ABSTRACT Endometrial cancer is the sixth most common cancer in women globally and has a rising incidence, accounting for 417,000 new diagnoses and more than 97,000 deaths in 2020. Early detection is critical because of a poor advanced-stage prognosis and high relapse risk. Postmenopausal bleeding precedes endometrial cancer in 90% of cases, yet only 5% to 10% of patients with this symptom have an underlying malignancy. Recent cytology research has demonstrated endometrial cancer cells in vaginal samples, suggesting urine and cervicovaginal self-samples may allow convenient and minimally invasive screening. In addition, screening samples for DNA methylation in tumor suppressor genes can increase testing efficacy of triaging patients with postmenopausal bleeding as it does not require intact tumor cells. This study aimed to evaluate the diagnostic performance of endometrial cancer detection using DNA methylation analysis in paired urine, cervicovaginal self-samples, and clinician-taken cervical scrapes. Paired samples from participants of the SOLUTION1 study with endometrial cancer were collected between October 2016 and August 2020. A complete urine void and cervicovaginal self-sample was collected at home, whereas the cervical scrape was taken by a clinician in the operating room before surgery. Each patient had a paired urine, cervicovaginal self-sample, and clinician-taken cervical scrape available for methylation analysis. Controls were collected from the Urine Controls (URIC) biobank and Dutch national cervical cancer screening program. Promoter hypermethylation of the ADCYAP1, BHLHE22, CDH13, CDO1, GALR1, GHSR, HAND2, SST, and ZIC1 genes was tested using quantitative methylation-specific polymerase chain reaction. Optimal 3-marker combinations were determined for each sample type using multivariable logistic regression analysis, and diagnostic performances of each marker and 3-marker panels were assessed by leave-one-out cross validation. A total of 103 endometrial cancer patients were included in this study, with 317 unpaired samples of control women. Methylation levels of all markers were significantly higher in all 3 sample types of endometrial cancer patients compared with healthy control women. In urine, the non–cross-validated area under the curve of the DNA methylation markers ranged between 0.61 and 0.93, in cervicovaginal self-samples between 0.62 and 0.91, and in clinician-taken cervical scrapes between 0.61 and 0.95. Most markers (7/9) showed the highest performance in urine, with the remaining 2 showing best performance in clinician-taken cervical scrapes. The optimal 3-marker combination panels showed area under the curve values of 0.95 (05% confidence interval [CI], 0.92–0.98) for urine, 0.94 (95% CI, 0.90–0.97) for cervicovaginal self-samples, and 0.97 (95% CI, 0.96–0.99) for clinician-taken cervical scrapes. The sensitivity and specificity of the optimal urine testing panel were both 90%, were 89% sensitivity and 92% specificity for cervicovaginal self-samples, and were 93% sensitivity and 90% specificity for clinician-taken cervical scrapes. The leave-one-out cross-validation analysis revealed virtually equal performances in marker panels for each of the 3 testing modalities. The results of this study demonstrate high diagnostic potential of DNA methylation testing in minimally and noninvasive samples for endometrial cancer detection, emphasizing the potential for patient-friendly home-based sample collection.

Counseling on the Importance of IVA Test for Early Detection of Cervical Cancer at Posyandu

Cervical cancer is a significant global health problem, especially in females. Early detection of cervical cancer is essential in reducing mortality from this disease. Visual Inspection with Acetic Acid (IVA) Test is an effective and affordable method to detect precancerous changes in the cervix. Knowledge of IVA tests and access to them can be challenging, especially in community environments such as Posyandu. Various strategies have been proposed to increase public understanding and awareness of the IVA Test. This includes training Posyandu cadres, socialization at Posyandu meetings, live demonstrations, and awareness campaigns. Partnerships with local health centres are also crucial for regular IVA Test services. By integrating these efforts, it is hoped that the public will be more aware of the importance of IVA tests for early detection of cervical cancer and have better access to this service. Doing so can increase the chances of early detection, reduce mortality from cervical cancer, and protect women's overall health

Detection of Age-Related Somatic Alterations in Canine Blood Using Next-Generation Sequencing-Based Liquid Biopsy: An Analysis of over 4800 Dogs.

Age-related somatic genomic alterations in hematopoietic cell lines have been well characterized in humans; however, this phenomenon has not been well studied in other species. Next-generation sequencing-based liquid biopsy testing for cancer detection was recently developed for dogs and has been used to study the genomic profiles of blood samples from thousands of canine patients since 2021. In this study, 4870 client-owned dogs with and without a diagnosis or suspicion of cancer underwent liquid biopsy testing by this method. Copy number variants detected exclusively in genomic DNA derived from white blood cells (WBC gDNA-specific CNVs) were observed in 126 dogs (2.6%; 95% CI: 2.2-3.1); these copy number variants were absent from matched plasma cell-free DNA, and from tumor tissue in dogs with concurrent cancer. These findings were more common in older dogs and were persistent in WBC gDNA in over 70% of patients, with little to no change in the amplitude of the signal across longitudinal samples. Many of these alterations were observed at recurrent locations in the genome across subjects; the most common finding was a partial loss on CFA25, typically accompanied by a partial gain on the same chromosome. These early findings suggest that age-related somatic alterations may be present at an appreciable frequency in the general canine population. Further research is needed to determine the clinical significance of these findings.

Capitalizing glycomic changes for improved biomarker-based cancer diagnostics.

Cancer serum biomarkers are valuable or even indispensable for cancer diagnostics and/or monitoring and, currently, many cancer serum markers are routinely used in the clinic. Most of those markers are glycoproteins, carrying cancer-specific glycan structures that can provide extra-information for cancer monitoring. Nonetheless, in the majority of cases, this differential feature is not exploited and the corresponding analytical assays detect only the protein amount, disregarding the analysis of the aberrant glycoform. Two exceptions to this trend are the biomarkers α-fetoprotein (AFP) and cancer antigen 19-9 (CA19-9), which are clinically monitored for their cancer-related glycan changes, and only the AFP assay includes quantification of both the protein amount and the altered glycoform. This narrative review demonstrates, through several examples, the advantages of the combined quantification of protein cancer biomarkers and the respective glycoform analysis, which enable to yield the maximum information and overcome the weaknesses of each individual analysis. This strategy allows to achieve higher sensitivity and specificity in the detection of cancer, enhancing the diagnostic power of biomarker-based cancer detection tests.

Tumor-educated platelet blood tests for Non-Small Cell Lung Cancer detection and management

Liquid biopsy approaches offer a promising technology for early and minimally invasive cancer detection. Tumor-educated platelets (TEPs) have emerged as a promising liquid biopsy biosource for the detection of various cancer types. In this study, we processed and analyzed the TEPs collected from 466 Non-small Cell Lung Carcinoma (NSCLC) patients and 410 asymptomatic individuals (controls) using the previously established thromboSeq protocol. We developed a novel particle-swarm optimization machine learning algorithm which enabled the selection of an 881 RNA biomarker panel (AUC 0.88). Herein we propose and validate in an independent cohort of samples (n = 558) two approaches for blood samples testing: one with high sensitivity (95% NSCLC detected) and another with high specificity (94% controls detected). Our data explain how TEP-derived spliced RNAs may serve as a biomarker for minimally-invasive clinical blood tests, complement existing imaging tests, and assist the detection and management of lung cancer patients.