Early Cancer Research Articles

Adenomatous Polyposis Coli (APC) Promoter Gene Methylation in Urine-Derived DNA: A Non-invasive Biomarker for Early Bladder Cancer Detection and Tumor Aggressiveness

Adenomatous Polyposis Coli (APC) Promoter Gene Methylation in Urine-Derived DNA: A Non-invasive Biomarker for Early Bladder Cancer Detection and Tumor Aggressiveness

MiRNA in Machine-Learning-Based Diagnostics of Oral Cancer.

MicroRNAs (miRNAs) are crucial regulators of gene expression, playing significant roles in various cellular processes, including cancer pathogenesis. Traditional cancer diagnostic methods, such as biopsies and histopathological analyses, while effective, are invasive, costly, and require specialized skills. With the rising global incidence of cancer, there is a pressing need for more accessible and less invasive diagnostic alternatives. This research investigates the potential of machine-learning (ML) models based on miRNA attributes as non-invasive diagnostic tools for oral cancer. Methods and Tools: We utilized a comprehensive methodological framework involving the generation of miRNA attributes, including sequence characteristics, target gene associations, and cancer-specific signaling pathways. The miRNAs were classified using various ML algorithms, with the BayesNet classifier demonstrating superior performance, achieving an accuracy of 95% and an area under receiver operating characteristic curve (AUC) of 0.98 during cross-validation. The model's effectiveness was further validated using independent datasets, confirming its potential clinical utility. Our findings highlight the promise of miRNA-based ML models in enhancing early cancer detection, reducing healthcare burdens, and potentially saving lives. This study paves the way for future research into miRNA biomarkers, offering a scalable and adaptable diagnostic approach for various cancers.

Preoperative Delta Neutrophil Index, Platelet Lymphocyte Ratio and Immature Granulocyte Count for Differentiating Metastatic Colon Cancer from Non-Metastatic Colon Cancer: A Retrospective Study.

Immature granulocytes show bone marrow activation before neutrophil response and there are studies in the literature showing that the number of immature granulocytes is an auxiliary marker in the diagnosis and treatment of different diseases. The Delta Neutrophil Index (DNI), Immature Granulocyte Count (IGC) have previously been studied as markers in thyroid and breast cancers. The aim of this study was to determine whether immature granulocyte IGC and DNI values measured in preoperative blood parameters have a diagnostic benefit for the detection of advanced colon cancer. A study was conducted on patients who had undergone selective operation for colon cancer in our clinic from February 2015 to February 2020. The patients were divided into two groups: early stage (stage I-III) and advanced stage (stage IV) colon cancer. The IGC and DNI values as well as other hematological parameters, demographic parameters (sex, age) in these two groups were compared. A total of 43 patients with mean age 67.47 (35-96) years were included in the study. Eighteen of the patients were male and 25 were female. When the early stage and advanced stage colon cancer groups were compared, no statistically significant difference was found between age, sex, white blood cell count, lymphocyte-to-monocyte ratio, eosinophil count, basophil count, mean platelet volume and: systemic immune-inflammation index score. It was observed that platelet-to-lymphocyte ratio, IGC and DNI or Immature Granulocyte Percentage (IGP) values were statistically significantly higher in the metastatic colon cancer group compared to the non-metastatic group. When the specificity and sensitivity of laboratory markers in metastatic colon cancer were examined, it was observed that the specificity and sensitivity of DNI or IGP and IGC were statistically higher than other values. DNI, IGC and PLR values, which are the parameters measured in the preoperative period are easily measurable laboratory parameters and do not involve additional costs in differentiating metastatic from non-metastatic colon cancer in the preoperative period.

Early onset Colorectal Cancer and its association with its histological subtypes

Objective: There are different clinicopathological features between early and late onset colorectal cancer. We aimed to characterize the histological features of colorectal cancer (CRC) at different age groups in our institution. Methods: Total 232 patients with histologically proven colorectal cancer between ages 13-99 were included. This is retrospective study. Data collected from tumour registry Shifa International Hospital from January 1st 2018 to December 31st 2020. Pearson Chi square test was used for significance of categorical variables. P-values less than 0.05 were considered significant. Results: Mean age at diagnosis was 55.49+/-16.43 years. Out of total 232 patients 58.6% were male and 41.3% were females (p value= 0.16). 150 (64.9%) were aged > 50 years and 81 (35.1%) were age < or equal to 50 years (p value = 0.44). Most common histological subtype was adenocarcinoma that was found in 188 (81%) cases. One hundred fifty five (66.8%) patients had Grade-II tumor, 67(28.9%) with Grade-III and 10 (4.3%) with Grade-I tumor. Fifty eight (25%) patients presented with metastatic disease. A significantly higher percentage of patients with signet ring cell cancer presented with a high-grade tumor when compared with patients with adenocarcinoma and mucinous carcinoma (93.7% vs 21.8%, p-value- <0.001%; 93.7% vs 39.2%, p-value <0.001).A significantly higher percentage of patients with mucinous adenocarcinoma and signet ring cell carcinoma presented at age less than 50 as compared to those with adenocarcinoma (60.7%, 56.2% and 30.8% respectively; p-value <0.05). Conclusion: This study signifies that mucinous and signet ring cell type CRC present at an early age and with a higher proportion of patients with high tumour grade. Early diagnosis is key to help improve outcomes in these patients. doi: https://doi.org/10.12669/pjms.40.10.10143 How to cite this: Ibrar F, Atiq M, Shafqat F, Khan HM. Early onset Colorectal Cancer and its association with its histological subtypes. Pak J Med Sci. 2024;40(10):2395-2399. doi: https://doi.org/10.12669/pjms.40.10.10143 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Cost-effectiveness analysis of simple hysterectomy compared to radical hysterectomy for early cervical cancer: analysis from the GCIG/CCTG CX.5/SHAPE trial.

SHAPE (Simple Hysterectomy And PElvic node assessment) was an international phase III trial demonstrating that simple hysterectomy was non-inferior to radical hysterectomy for pelvic recurrence risk, but superior for quality of life and sexual health. The objective was to conduct a cost-effectiveness analysis comparing simple vs. radical hysterectomy for low-risk early-stage cervical cancer. Markov model compared the costs and benefits of simple vs. radical hysterectomy for early cervical cancer over a 5-year time horizon. Quality-adjusted life years (QALYs) were estimated from health utilities derived from EQ-5D-3L surveys. Sensitivity analyses accounted for uncertainty around key parameters. Monte Carlo simulation estimated complication numbers according to surgical procedure. Simple hysterectomy was more effective and less costly than radical hysterectomy. Average overall costs were $11,022 and $12,533, and average gains were 3.56 and 3.54 QALYs for simple and radical hysterectomy, respectively. Baseline health utility scores were 0.81 and 0.83 for simple and radical hysterectomy, respectively. By year 3, these scores improved for simple hysterectomy (0.82) but not for radical hysterectomy (0.82). Assuming 800 early cervical cancer patients annually in Canada, the model estimated 3 vs. 82 patients with urinary retention, and 49 vs. 86 patients with urinary incontinence persisting 4 weeks after simple vs. radical hysterectomy, respectively. Results were most sensitive to variability in health utilities after surgery, but stable through wide ranges of costs and recurrence estimates. Simple hysterectomy is less costly and more effective in terms of quality-adjusted life expectancy compared to radical hysterectomy for early cervical cancer. ClinicalTrials.gov Identifier: NCT01658930.

Early Onset Pancreatic Adenocarcinoma (EOPAC): presentation, clinical course and treatment outcomes in comparison to Average Onset Pancreatic Adenocarcinoma (AOPAC): a retrospective cohort study

BackgroundPancreatic adenocarcinoma (PAC) is a disease of decimal prognosis, with around 50% of patients presenting with metastatic disease. Previous trials reported a high incidence of early onset pancreatic cancer (EOPAC) in Egypt, presenting about 25% of patients with PAC. The clinic-pathological features and prognosis of EOPAC needs more study.Patients and methodsA retrospective analysis of patients’ records at Shefa Al-Orman comprehensive cancer center database. Patients with histo-pathologically confirmed diagnosis of PAC. We categorized patients according to the age at diagnosis into EOPAC (≤ 50 years) and average onset PAC (AOPAC). Data on risk factors, family history, presenting symptoms, clinic-pathological features, treatment, and prognosis were extracted. Patients with histopathologically confirmed diagnosis of pancreatic cancer diagnosed between December 2016-December 2022 were included.ResultsThe study cohort consisted of 412 patients. EOPAC represented 20.3% of patients, with no significant differences in risk factors and family history compared to AOPAC. Duration of symptoms before diagnosis is longer in EOPAC, with the majority of EOPAC presenting with localized disease (23.8%) and locally advanced tumors (28.5%) compared to AOPAC. AOPAC presented more with metastatic disease (64% vs. 45.2%, p = 0.003). EOPAC are usually submitted to more aggressive treatment including radical surgery, neoadjuvant therapy, and aggressive chemotherapy regimens in metastatic disease. Disease free survival (DFS) of EOPAC was shorter than AOPAC (11 months vs. 17 months, p = 0.889), but overall survival OS was significantly longer in EOPAC (10 months vs. 6 months, p = 0.013).ConclusionPatients with EOPAC in Egypt represent around 25% of cases. EOPAC tend to have a shorter disease free survival (DFS) in patients presenting with localized disease. The overall survival (OS) is longer in EOPAC compared to AOPAC. Further studies are mandatory to identify the epidemiological and risk factors of EOPAC in Egypt.

Effect of a Physical Exercise Intervention on Physical Function Parameters and Blood Analytical Changes in Lung Cancer Survivors: A Feasibility Study.

Background: Lung cancer carries a high burden of systemic symptoms, including in survivors, leading to a reduced quality of life (QoL). We assessed whether a 12-week multicomponent supervised exercise programme, including muscular strength and aerobic training, was beneficial in patients who had undergone surgery for early non-small cell lung cancer (NSCLC) in terms of physical performance, QoL, and metabolic and nutritional analytical parameters. Methods: Physical performance was measured by gait speed, handgrip strength, 30 s sit-to-stand (30s-STS) test repetitions, distance covered in the 6 min walk test (6MWT), and the Short Physical Performance Battery (SPPB) score. QoL was assessed with the EORTC-QLQ-C30 questionnaire. Blood glucose, cholesterol, triglycerides, total proteins, albumin, pre-albumin, creatinine, c-reactive protein, insulin-growth factor 1 (IGF-1), and the haemoglobin and hematocrit percentages were measured before and after the intervention in order to observe any beneficial effects related to metabolic markers. Results: After the intervention, the mean scores for the 6MWT (p < 0.001), STS (p < 0.001), 6MWT (p < 0.01), and SPPB (p < 0.01) had significantly improved. However, handgrip strength and nutritional analytical were unchanged. The EORTC-QLQ-C30 functions and symptoms significantly improved after the intervention (p < 0.05 and p < 0.01, respectively). A significant decrease in cholesterol, triglycerides, and IGF-1 and a significant increase in pre-albumin in blood was also observed post-intervention (p < 0.05). Conclusions: This supervised, community-based 12-week multicomponent was feasible (adherence rate 70.35%) and provided benefits not only to physical performance but also to the quality of life of patients with NSCLC.

Early Cancer Detection via Multi-microRNA Profiling of Urinary Exosomes Captured by Nanowires.

Multiple microRNAs encapsulated in extracellular vesicles (EVs) including exosomes, unique subtypes of EVs, differ in healthy and cancer groups of people, and they represent a warning sign for various cancer scenarios. Since all EVs in blood cannot be transferred from donor to recipient cells during a single blood circulation, kidney filtration could pass some untransferred EVs from blood to urine. Previously, we reported on the ability of zinc oxide nanowires to capture EVs based on surface charge and hydrogen bonding; these nanowires extracted massive numbers of microRNAs in urine, seeking cancer-related microRNAs through statistical analysis. Here, we report on the scalability of the nanowire performance capability to comprehensively capture EVs, including exosomes, in urine, extract microRNAs from the captured EVs in situ, and identify multiple microRNAs in the extracted microRNAs differing in noncancer and lung cancer subjects through machine learning-based analysis. The nanowire-based extraction allowed the presence of about 2500 species of urinary microRNAs to be confirmed, meaning that urine includes almost all human microRNA species. The machine learning-based analysis identified multiple microRNAs from the extracted microRNA species. The ensembles could classify cancer and noncancer subjects with the area under the receiver operating characteristic curve of 0.99, even though the former were staged early.

Roles of microRNA-486-5p in the diagnosis and the association with clinical symptoms of cervical cancer.

Aim: To explore the predictive value of miR-486-5p in early cervical cancer and the associations of miR-486-5p with different clinical symptoms.Materials & methods: A total of 185 women were recruited. The relative expression levels of serum miR-486-5p were analyzed by real-time polymerase chain reaction. The receiver operator characteristic curves were utilized to reflect the predictive performance of miR-486-5p and squamous cell carcinoma antigen for early cervical cancer. Univariate logistic regression and ranked logistic regression were used to explore the associations of miR-486-5p with different clinical symptoms of early cervical cancer, with odd ratios (ORs) and 95% confidence intervals.Results: Eighty-one women (44.26%) had early cervical cancer. The relative expression of serum miR-486-5p was 1.99-fold higher in early cervical cancer patients than that in controls (p<0.0001). The predictive performance of miR-486-5p for early cervical cancer was significantly superior to that of squamous cell carcinoma antigen, with an area under the curve of 0.865 (p<0.001), sensitivity of 1.000and specificity of 0.804. In addition, overexpressed miR-486-5p was associated with high odds of maximum tumor diameter increase (OR=1.30, 95%CI: [1.01-1.66]).Conclusion: MiR-486-5p may be a potential biomarker for the early cervical cancer diagnosis, and was linked to the risk of maximum tumor diameter.

EXPRESS: Early Onset Colorectal Cancer, not just the Age: data from a large health organization.

Early onset colorectal cancer (EO-CRC) is increasing. We investigated the risk factors for ER-CRC compared to late onset CRC (LO-CRC). CRC patients between the years 1999 and 2021 were retrospectively evaluated. Data regarding demographics, comorbidities, malignancies, and mortality were collected. Data were retrieved using the MdClone platform from a large Health Maintenance Organization. The cohort was subdivided into EO-CRC (age ≤50 years) and LO-CRC (age ≥51 years) groups. 61,679 patients diagnosed with CRC were included in our analysis, 30,456 (49.4%) males, and 4,891 (7.9%) Arabs, with an average age at diagnosis of 70.1±13.1 years. 5561 (9%) patients were included in the EO-CRC group. Over the last decades, higher rates of EO-CRC were diagnosed compared to the previous decade, 9.8% vs 8.3%, p<0.001. A higher percentage of EO-CRC patients were females (52.8% vs 50.4%), had a family history of CRC (9.9% vs 5.5%), were Arabs (18.7% vs 6.9%), and were smokers (32.7% vs 30.2%) compared to LO-CRC patients. Significantly lower rates of comorbidities such as ischemic heart disease, diabetes mellitus, hypertension, obesity, and iron deficiency anemia were found among EO-CRC patients, with a lower all-cause mortality (27.7% vs 63.1%, p<0.001). 348 (6.3%) of the EO-CRC patients had another Lynch-related cancer until age 50 years compared to 45 (0.1%) at the LO-CRC. Young individuals with increased risk for CRC need special consideration and should be referred early for screening and endoscopic investigation, particularly those with a family history of CRC, smokers, and those of Arab ethnicity.

Bedside to bench and back again-translational research in interventional pulmonology.

Translational research in Interventional Pulmonology has made significant advances in recent years, ranging from novel biomarkers and imaging to practice-changing clinical trials in lung cancer and pleural disease. This review article aims to summarize key research studies in the field to understand the latest published evidence and to highlight areas of growing academic interest. In lung cancer, the role of novel imaging and biomarkers and their potential utility in early lung cancer diagnosis will be highlighted. In pleural disease, less invasive/conservative treatment in pneumothorax, early aggressive treatment in pleural infection along with novel biomarkers, and the shift beyond drainage strategies in malignant pleural effusion and mesothelioma will be discussed. This overview of translational research in the field of interventional pulmonology will ultimately help to highlight the gaps in current evidence to promote research in areas of clinical significance.

The RECONCILE study protocol: Exploiting image-based risk stratification in early prostate cancer to discriminate progressors from non-progressors (RECONCILE).

RECONCILE (ClinicalTrials.gov:NCT04340245) will identify molecular and radiomic markers associated with clinical progression and radiological progression events in a cohort of localised, newly diagnosed Gleason 3 + 4 tumours. Molecular markers will be correlated against standard of care MRI-targeted histology and oncological outcomes. RECONCILE is an ethics approved (20/LO/0366) single centre, prospective, longitudinal, observational cohort study of recently diagnosed (within 12 months), organ-confined Gleason 3 + 4 cancers (MCCL ≤10mm) currently under active surveillance. 60 treatment-naïve participants with a concordant MRI lesion (Likert score 4 or 5) and PSA ≤ 15 ng/ml will be recruited. Blood, urine and targeted prostate tissue cores will be subject to next generation sequencing at baseline and one year in all participants. Semen will be collected from a specified sub-population. Baseline and interval MR images will be extracted from standard of care prostate MRI ahead of radiomic analysis. Data extracted from radiological and biological samples will be used to derive the association of molecular change and radiological progression, the primary outcome of the study. To compensate for spatial intratumoral heterogeneity and inherent sampling bias, a molecular index will be derived for each participant using the molecular profile of tumour tissue at both baseline (MolBL) and one year (MolFU). We will extract a ΔMolBL:MolFU score for each participant. Molecular progression will be defined as a MolBL:MolFU score >95% CI of the combined ΔMolBL scores. Radiological progression is defined as a PRECISE score of 4 or 5. The study is powered to detect an association with a statistical power of 80%. Recruitment began in July 2020 (n = 62). To date, 37 participants have donated tissue for analysis. We have designed and implemented a prospective, longitudinal study to evaluate the underlying molecular landscape of intermediate risk, MR-visible prostate tumours. Recruitment is ongoing.

Machine learning-derived peripheral blood transcriptomic biomarkers for early lung cancer diagnosis: Unveiling tumor-immune interaction mechanisms.

Lung cancer continues to be the leading cause of cancer-related mortality worldwide. Early detection and a comprehensive understanding of tumor-immune interactions are crucial for improving patient outcomes. This study aimed to develop a novel biomarker panel utilizing peripheral blood transcriptomics and machine learning algorithms for early lung cancer diagnosis, while simultaneously providing insights into tumor-immune crosstalk mechanisms. Leveraging a training cohort (GSE135304), we employed multiple machine learning algorithms to formulate a Lung Cancer Diagnostic Score (LCDS) based on peripheral blood transcriptomic features. The LCDS model's performance was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC) in multiple validation cohorts (GSE42834, GSE157086, and an in-house dataset). Peripheral blood samples were obtained from 20 lung cancer patients and 10 healthy control subjects, representing an in-house cohort recruited at the Sixth People's Hospital of Chengdu. We employed advanced bioinformatics techniques to explore tumor-immune interactions through comprehensive immune infiltration and pathway enrichment analyses. Initial screening identified 844 differentially expressed genes, which were subsequently refined to 87 genes using the Boruta feature selection algorithm. The random forest (RF) algorithm demonstrated the highest accuracy in constructing the LCDS model, yielding a mean AUC of 0.938. Lower LCDS values were significantly associated with elevated immune scores and increased CD4+ and CD8+ T-cell infiltration, indicative of enhanced antitumor-immune responses. Higher LCDS scores correlated with activation of hypoxia, peroxisome proliferator-activated receptor (PPAR), and Toll-like receptor (TLR) signaling pathways, as well as reduced DNA damage repair pathway scores. Our study presents a novel, machine learning-derived peripheral blood transcriptomic biomarker panel with potential applications in early lung cancer diagnosis. The LCDS model not only demonstrates high accuracy in distinguishing lung cancer patients from healthy individuals but also offers valuable insights into tumor-immune interactions and underlying cancer biology. This approach may facilitate early lung cancer detection and contribute to a deeper understanding of the molecular and cellular mechanisms underlying tumor-immune crosstalk. Furthermore, our findings on the relationship between LCDS and immune infiltration patterns may have implications for future research on therapeutic strategies targeting the immune system in lung cancer.

P4.07E.03 Real-World Data on Early Lung Cancer in Never-Smokers and Light Smokers-Prevalence, Family History, and Molecular Alterations

P4.07E.03 Real-World Data on Early Lung Cancer in Never-Smokers and Light Smokers-Prevalence, Family History, and Molecular Alterations

OA17.03 Missed Opportunities for Early Lung Cancer Detection in a Multi-Disciplinary Thoracic Oncology Clinic Cohort

OA17.03 Missed Opportunities for Early Lung Cancer Detection in a Multi-Disciplinary Thoracic Oncology Clinic Cohort

The Impact of the COVID-19 Lockdown on Cancer Referrals in Primary Care in the UK: Two Years On

Background: Cancer is common, with most cancer patients presenting initially to a general practitioner. The COVID-19 pandemic led to changes in the delivery of primary care, which could have affected cancer referrals. This observational study looked at two-week cancer referrals (2WRs) made before, during and after the first UK COVID-19 lockdown in 2020, at a GP practice in the Wirral, England. Methods: A search was conducted to find the cancer referrals made between 23rd March 2020 - 1st July 2020, during the first lockdown. Using the same methodology, cancer referral data was collected for the corresponding time periods in 2019 and 2021. The number of 2WRs and positive diagnostic yields were then compared. Results: The number of cancer referrals decreased by 40.4% in 2020, compared to 2019. In 2021, the number of referrals then increased by 225%, compared to 2020. Overall, the number of cancer referrals increased between 2019-2021. The positive diagnostic yield for the 2020 2WRs increased by 251.4%, compared to that of 2019. The calculated yield for the 2021 data then decreased by 10.8% compared to 2020. Overall, the positive diagnostic yield increased between 2019-2021. Conclusion: The numbers and outcomes of cancer referrals at this Wirral GP practice have changed considerably following the first UK COVID-19 lockdown in 2020, and the influence of the pandemic was still affecting cancer referrals in 2021. A greater focus on early cancer detection in primary care could help overcome the ways in which the pandemic has affected primary care delivery.

Long-Term Laryngeal Function and Quality of Life Following Treatment of Early Glottic Cancer: A Meta-Analysis.

To review the literature concerning long-term functional outcomes and quality of life (QoL) in patients undergoing transoral laser microsurgery (TLM) versus radiotherapy (RT) for early glottic cancer. A systematic search was conducted across PubMed, Scopus, and Cochrane Library from inception until April 2024. Articles considered were primary studies directly comparing the 2 treatment modalities in a population of T1 and T2 glottic cancer. Interest outcomes were patient report outcome measures (PROMs) of vocal function and QoL, clinician-reported measures, and acoustic analyses parameters. There was no significant difference between TLM and RT in grade, roughness, breathiness, asthenia, strain (relative risk, 1.11; 95% confidence interval [CI], 0.60-2.07; I2 = 90.96; P < .001), Voice Handicap Inventory-30 scores (standardized mean difference [SME] 0.51; 95% CI, -0.04-1.07; I2 = 89.72; P < .001), or fundamental frequency (SME 0.56; 95% CI, -0.14-1.25; I2 = 91.12; P < .001). The TLM group had significantly better performance with regards to jitter (SME 0.54; 95% CI, 0.08-1.00; I2 = 79.42; P < .001) and shimmer (SME 0.53; 95% CI, 0.11-0.95; I2 = 74.94; P < .001). The risk of bias was assessed to be serious. The findings suggest comparable long-term PROMs between TLM and RT in the treatment of early glottic carcinoma, with TLM showing better acoustic analysis outcomes. However, the available evidence remains scarce, of high heterogeneity, and at risk of bias. A direct comparison between TLM and RT through large randomized controlled trials is needed to provide more substantial evidence to determine the optimum treatment.

Differential methylation of circulating free DNA assessed through cfMeDiP as a new tool for breast cancer diagnosis and detection of BRCA1/2 mutation

BackgroundRecent studies have highlighted the importance of the cell-free DNA (cfDNA) methylation profile in detecting breast cancer (BC) and its different subtypes. We investigated whether plasma cfDNA methylation, using cell-free Methylated DNA Immunoprecipitation and High-Throughput Sequencing (cfMeDIP-seq), may be informative in characterizing breast cancer in patients with BRCA1/2 germline mutations for early cancer detection and response to therapy.MethodsWe enrolled 23 BC patients with germline mutation of BRCA1 and BRCA2 genes, 19 healthy controls without BRCA1/2 mutation, and two healthy individuals who carried BRCA1/2 mutations. Blood samples were collected for all study subjects at the diagnosis, and plasma was isolated by centrifugation. Cell-free DNA was extracted from 1 mL of plasma, and cfMeDIP-seq was performed for each sample. Shallow whole genome sequencing was performed on the immuno-precipitated samples. Then, the differentially methylated 300-bp regions (DMRs) between 25 BRCA germline mutation carriers and 19 non-carriers were identified. DMRs were compared with tumor-specific regions from public datasets to perform an unbiased analysis. Finally, two statistical classifiers were trained based on the GLMnet and random forest model to evaluate if the identified DMRs could discriminate BRCA-positive from healthy samples.ResultsWe identified 7,095 hypermethylated and 212 hypomethylated regions in 25 BRCA germline mutation carriers compared to 19 controls. These regions discriminate tumors from healthy samples with high accuracy and sensitivity. We show that the circulating tumor DNA of BRCA1/2 mutant breast cancers is characterized by the hypomethylation of genes involved in DNA repair and cell cycle. We uncovered the TFs associated with these DRMs and identified that proteins of the Erythroblast Transformation Specific (ETS) family are particularly active in the hypermethylated regions. Finally, we assessed that these regions could discriminate between BRCA positives from healthy samples with an AUC of 0.95, a sensitivity of 88%, and a specificity of 94.74%.ConclusionsOur study emphasizes the importance of tumor cell-derived DNA methylation in BC, reporting a different methylation profile between patients carrying mutations in BRCA1, BRCA2, and wild-type controls. Our minimally invasive approach could allow early cancer diagnosis, assessment of minimal residual disease, and monitoring of response to therapy.

Predictive Value of Multi-Phase CT Radiomics in Delineating Early and Advanced T Staging of Colon Cancer

This study leveraged the power of multi-phase CT radiomics, which extracts detailed features from multi-phase images, to explore the distinction between early (T1-T2) and advanced (T3-T4) colon cancer stages in each of multiple phases, providing valuable insights to healthcare professionals and enhancing their decision-making capabilities. A total of 191 patients with surgically confirmed primary colon cancer were retrospectively included, and multi-phase CT scans (non-enhanced contrast phase, arterial phase, portal venous phase, and delayed phase) were conducted within one week before surgery. Three-dimensional segmentation of colonic tumors was performed on the images of the four phases, and radiomics features of each colonic tumor were automatically extracted. Minimum redundancy maximum relevance (mRMR) was applied to features selection in each of the four phases. The least absolute shrinkage and selection operator logistic regression was conducted to determine the association between radiomics features and early (T1-T2) and advanced (T3-T4) stages of colon cancer. Additionally, diagnostic performance comparison was carried out in four phases. The mean (±SD) age of the 191 individuals was 61.87±13.137 years, with females comprising 43.5% of the cohort. The selected features for the non-enhanced, arterial, portal venous, and delayed phases numbered 7, 11, 6, and 10, respectively. In the test set, the AUC values for the on-enhanced, arterial, portal venous, and delayed phases were 0.86 (0.76-0.96), 0.84 (0.73-0.94), 0.82 (0.71-0.93), and 0.86 (0.75-0.97), with corresponding accuracies of 0.84, 0.80, 0.75, and 0.88, sensitivities of 0.73, 0.64, 0.86, and 0.68, and specificities of 0.91, 0.91, 0.68, and 1.00, respectively. DeLong's test revealed no statistically significant differences in the AUC values between the four phases within the test sets (P = 0.3233~ 0.9912). Multi-phase CT radiomics demonstrated substantial value in differentiating between early (T1-T2) and advanced (T3-T4) stages of patients with colon cancer.

Key issues in diagnostic accuracy of sentinel lymph node biopsy in early-stage ovarian cancer: systematic review and meta-analysis

ObjectiveSentinel lymph node (SLN) mapping may reduce the morbidity of lymphadenectomy while maintaining diagnostic accuracy. Nevertheless, SLN mapping in epithelial ovarian cancer is still under investigation. This systematic review and...