Non-cancer Individuals Research Articles

Evaluation of cfDNA fragmentation characteristics in plasma for the diagnosis of lung cancer: A prospective cohort study.

Lung cancer is one of the most prevalent cancers worldwide, yet only approximately 16% of patients are diagnosed in early stage, highlighting the urgent need for novel, highly accurate detection models. In our study, patients with suspected lung cancer or lung disease, as identified through radiographic imaging, along with healthy individuals, were consecutively recruited from Beijing Chest Hospital. Circulating free DNA (cfDNA) was extracted from plasma samples, and low-depth whole-genome sequencing was performed to identify fragmentomic features for model construction. A total of 265 participants were prospectively enrolled, comprising 124 lung cancer patients and 141 noncancer individuals. The model we developed was based on four cfDNA fragmentation characteristics, including 20-bp breakpoint nucleotides motif, fragmentation size coverage, fragmentation size distribution, and copy number variation. In an independent test cohort, the model achieved an area under the curve (AUC) of 0.861 (95% CI: 0.781-0.942) and demonstrated a sensitivity of 70% (95% CI: 53.5%-83.4%) at a specificity of 89.4% (95% CI: 76.9%-96.5%). Notably, the model was also effective in detecting early-stage cancer, with an AUC of 0.808 (95% CI: 0.69-0.925). In summary, our lung cancer detection model shows strong screening capabilities by leveraging four cfDNA fragmentation characteristics, exhibiting robust performance in early cancer diagnosis.

Healthcare use among cancer survivors during the COVID-19 pandemic: results from the SHARE COVID-19 Survey

PurposeTo estimate the association between a previous cancer diagnosis and healthcare use during the COVID-19 pandemic among Europeans and Israelis individuals.MethodsThis cross-sectional study was based on data from the Survey of Health, Ageing and Retirement in Europe (SHARE), including the SHARE COVID-19 Survey, which was conducted in the summer of 2020, in 27 countries. Cancer survivors (CS, n = 6409) were country-, sex-, age-, and education-matched (1:2) to non-cancer individuals (NC). Adjusted odds ratios (OR) and 95% confidence intervals (95%CI) were computed using logistic regression.ResultsOverall, CS were more likely to refer that they forwent medical appointments due to fear of COVID-19 (OR = 1.29, 95%CI 1.19–1.41) than NC, particularly those who lived with their partner and other relatives (OR = 1.79, 95%CI 1.39–2.30). Likewise, CS had their medical appointments postponed more often (OR = 1.54, 95%CI 1.44–1.64); this association was stronger among CS who lived with their partner and other relatives (OR = 1.96, 95%CI 1.63–2.36) who reported higher economic difficulties (OR = 1.73, 95%CI 1.50–2.00) and those with no multimorbidity (OR = 1.85, 95%CI 1.62–2.11). CS were also more likely to refer that they were unable to book an appointment (OR = 1.43, 95%CI 1.26–1.63), particularly those who reported that a person close to them died due to COVID-19 (OR = 2.72, 95%CI 1.47–5.01).ConclusionCS were more likely to forgo medical treatment, report healthcare postponements, and be unable to book an appointment than NC, which highlights the importance of closely monitoring the long-term impact of the COVID-19 pandemic along the cancer care continuum.

5-Hydroxymethylcytosines in circulating cell-free DNA as a diagnostic biomarker for nasopharyngeal carcinoma

ObjectiveTo evaluate the diagnostic value of 5-hydroxymethylcytosines (5hmC) in circulating cell-free DNA (cfDNA) for nasopharyngeal carcinoma (NPC) and to develop a diagnostic model. MethodsGenome-wide 5hmC profiles in cfDNA from 174 NPC patients and 146 non-cancer individuals were analyzed using the 5hmC-Seal technique. A cfDNA 5hmC-based diagnostic model to identify NPC patients was developed using least absolute shrinkage and selection operator (LASSO) logistic regression, and performance was evaluated with receiver operating characteristic (ROC) curves and confusion matrices. ResultsThe 5hmC-Seal data from patients with NPC showed a different genome-wide distribution than non-tumor samples. Our initial analysis revealed a 12-gene-based 5hmC marker panel to be an accurate diagnostic model effectively distinguishing between NPC samples and non-cancerous samples (training set: area under curve (AUC)= 0.97 [95 % CI: 0.94–0.99]; and test set: AUC= 0.93 [95 % CI: 0.88–0.98]) superior to EBV DNA testing. The diagnostic score performed well in differentiating the non-cancer subjects from early-stage NPC (training set: AUC=0.99 [95 % CI: 0.98–1]; test set: AUC=0.98 [95 % CI: 0.95–1]), and advanced-stage NPC (training set: AUC=0.96 [95 % CI: 0.93–0.99]; test set: AUC=0.93 [95 % CI: 0.88–0.98]). Notably, in EBV-negative patients, the diagnostic scores showed excellent capacity for distinguishing EBV-negative patients with NPC from non-cancer subjects in both the training set (AUC= 0.94 [95 % CI: 0.88–1]) and test set (AUC=0.91 [95 % CI: 0.81–1]). Conclusion5hmC modifications in cfDNA are promising noninvasive biomarkers for NPC, offering high sensitivity and specificity, particularly for early-stage and EBV-negative NPC.

Financial Distress in Genitourinary Cancer: Insights From CDC National Health Interview Survey.

This study leverages CDC National Health Interview Survey data to examine Financial Distress (FD) among genitourinary (GU) cancer survivors, specifically prostate cancer (PC), kidney cancer (KC), and bladder cancer (BC). It investigates the economic impacts faced by these patients, especially in relation to disparities in insurance coverage and its effects on material, psychological, and behavioral aspects of FD. We retrospectively analyzed responses from GU cancer survivors, stratifying by cancer status and age (18-64 years, ≥65 years). Medical financial hardship was divided into three domains: material, psychological, and behavioral. Associations between cancer history, hardship, and clinical factors were assessed using generalized ordinal logistic regressions. Significant health care access disparities were found, particularly for mental health services, with 25% of younger BC survivors and 4.7% of younger KC survivors reporting affordability issues, in contrast to 2.7% of noncancer individuals. Dental care was also problematic, with higher avoidance rates among younger BC (27%) and KC (15%) survivors compared with the general population. Surprisingly, noncancer individuals reported more difficulty in affording prescriptions than BC survivors across both age groups. PC survivors, however, showed lower FD across all domains versus noncancer controls, indicating fewer concerns about medical bills and a lesser tendency to forgo care. The study underscores significant gaps in the financial support system for GU cancer survivors, with urgent needs in mental and dental health care access. Policy interventions, including comprehensive insurance reforms, are imperative to alleviate the financial burdens on these individuals.

Gut microbiota Parabacteroides distasonis enchances the efficacy of immunotherapy for bladder cancer by activating anti-tumor immune responses

ObjectiveBladder cancer(BCa) was a disease that seriously affects patients’ quality of life and prognosis. To address this issue, many researches suggested that the gut microbiota modulated tumor response to treatment; however, this had not been well-characterized in bladder cancer. In this study, our objective was to determine whether the diversity and composition of the gut microbiota or the density of specific bacterial genera influence the prognosis of patients with bladder cancer.MethodsWe collected fecal samples from a total of 50 bladder cancer patients and 22 matched non-cancer individuals for 16S rDNA sequencing to investigate the distribution of Parabacteroides in these two groups. Further we conducted follow-up with cancer patients to access the impact of different genera of microorganisms on patients survival. We conducted a Fecal Microbiota Transplantation (FMT) and mono-colonization experiment with Parabacteroides distasonis to explore its potential enhancement of the efficacy of anti-PD-1 immunotherapy in MB49 tumor-bearing mice. Immunohistochemistry, transcriptomics and molecular experiment analyses were employed to uncover the underlying mechanisms.ResultsThe 16S rDNA showed that abundance of the genus Parabacteroides was elevated in the non-cancer control group compared to bladder cancer group. The results of tumor growth curves showed that a combination therapy of P. distasonis and ICIs treatment significantly delayed tumor growth and increased the intratumoral densities ofboth CD4+T and CD8+T cells. The results of transcriptome analysis demonstrated that the pathways associated with antitumoral immune response were remarkably upregulated in the P. distasonis gavage group.ConclusionP. distasonis delivery combined with α-PD-1 mAb could be a new strategy to enhance the effect of anti-PD-1 immunotherapy. This effect might be achieved by activating immune and antitumor related pathways.

Multi-dimensional cell-free DNA-based liquid biopsy for sensitive early detection of gastric cancer

BackgroundGastric cancer is the fifth most common cancer type. Most patients are diagnosed at advanced stages with poor prognosis. A non-invasive assay for the detection of early-stage gastric cancer is highly desirable for reducing associated mortality.MethodsWe collected a prospective study cohort of 110 stage I–II gastric cancer patients and 139 non-cancer individuals. We performed whole-genome sequencing with plasma samples and profiled four types of cell-free DNA (cfDNA) characteristics, fragment size pattern, copy number variation, nucleosome coverage pattern, and single nucleotide substitution. With these differential profiles, we developed an ensemble model to detect gastric cancer signals. Further, we validated the assay in an in-house first validation cohort of 73 gastric cancer patients and 94 non-cancer individuals and an independent second validation cohort of 47 gastric cancer patients and 49 non-cancer individuals. Additionally, we evaluated the assay in a hypothetical 100,000 screening population by Monte Carlo simulation.ResultsOur cfDNA-based assay could distinguish early-stage gastric cancer from non-cancer at an AUROC of 0.962 (95% CI: 0.942–0.982) in the study cohort, 0.972 (95% CI: 0.953–0.992) in the first validation cohort and 0.937 (95% CI: 0.890–0.983) in the second validation cohort. The model reached a specificity of 92.1% (128/139) and a sensitivity of 88.2% (97/110) in the study cohort. In the first validation cohort, 91.5% (86/94) of non-cancer individuals and 91.8% (67/73) of gastric cancer patients were correctly identified. In the second validation cohort, 89.8% (44/49) of non-cancer individuals and 87.2% (41/47) of gastric cancer patients were accurately classified.ConclusionsWe introduced a liquid biopsy assay using multiple dimensions of cfDNA characteristics that could accurately identify early-stage gastric cancer from non-cancerous conditions. As a cost-effective non-invasive approach, it may provide population-wide benefits for the early detection of gastric cancer.Trial registrationThis study was registered on ClinicalTrials.gov under the identifier NCT05269056 on March 7, 2022.

Multi-dimensional cell-free DNA-based liquid biopsy for sensitive detection of head and neck squamous cell carcinomas.

e18054 Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type worldwide. The mortality from HNSCC is closely linked to stage. However, the majority of HNSCC patients were diagnosed at an advanced stage. Therefore, a non-invasive assay for the early detection of HNSCCs is highly desirable for reducing the associated mortality. Methods: We collected a study cohort of 281 participants including 140 pathologically confirmed with head and neck squamous cell carcinomas (HNSCCs) and 141 with non-cancerous conditions. A plasma sample was collected from each participant along with general health screening examinations before any invasive examinations. We performed low-pass whole-genome sequencing with plasma samples and profiled three types of cell-free DNA (cfDNA) characteristics, fragment size pattern (FSP), copy number variation (CNV), and single nucleotide substitution (SNS). We developed an ensemble model with these differential profiles to identify HNSCC patients from non-cancer individuals. We further collected a validation cohort consisting of 90 HNSCC patients and 95 non-cancer individuals to validate the cfDNA-based assay. Results: The liquid biopsy assay that incorporated three types of cfDNA characteristics was able to identify HNSCC patients from non-cancer individuals at an AUROC of 0.989 in the study cohort and 0.984 in the validation cohort. At a specificity of 95.7% (135/141), it achieved a sensitivity of 95.7% (134/140) in the study cohort. With this threshold (0.580), in the validation cohort, 93.7% (89/95) of non-cancer individuals and 93.3% (84/90) of HNSCC patients were correctly identified. Specifically, the sensitivities in early stage (I&II) HNSCCs were 94.5 % (52/55) and 87.5% (28/32) in the study and validation cohort, respectively. Of note, the inferred probabilities of cancer showed consistent trends to increase with pathological stages in both cohorts (P=0.032 and 0.047, respectively). On the contrary, the differentiation grades and sub-locations did not significantly affect the performance of the assay. Conclusions: We introduced a liquid biopsy assay using multiple dimensions of cfDNA characteristics that could accurately identify HNSCCs from non-cancerous conditions. As a cost-effective non-invasive approach, it may be conveniently incorporated into annual general physical examinations to provide supplementary information about the risk of HNSCCs.

Precise health perspectives: Unraveling the interplay of reproductive factors in hormone receptor–positive and triple-negative breast cancer among Bangladeshi women.

e22503 Background: Breast cancer is a major cause of cancer-related deaths in Bangladesh, with an incidence rate of 22.5 per 100,000 females per year. Urbanization is linked to the increasing incidence of breast cancer, altering lifestyles and reproductive behaviors. Reproductive factors play a key role in breast cancer risk, with variations between TNBC and Hr+BC. This study aims to investigate the relationship between TNBC and Hr+BC and reproductive factors among Bangladeshi women to provide valuable insights for breast cancer prevention and management in the region. Methods: Conducted in a tertiary hospital-based setting, our survey included 1000 adult Bangladeshi females aged 18 or older. Among them, 250 had TNBC, 250 had Hr+BC, and the remaining 500 were non-cancer individuals. Propensity score matching (PSM) was utilized to match the age and age of menarche of 500 healthy individuals with 250 TNBC and 250 Hr+BC individuals separately. The presence of TNBC or Hr+BC was confirmed through participants' previous histopathology reports. Detailed reproductive characteristics and demographics were collected using a structured questionnaire. Significant variables identified in the bivariate model were included in the adjusted multivariable multinomial logistic regression. Results: Demographic and reproductive characteristics in the Hr+BC, TNBC, and healthy groups were analyzed. The mean ±SEM age was Hr+BC (44.96±0.65), TNBC (42.74±0.65), and healthy (39.31±0.55) years. Patients with Hr+BC and TNBC, compared to healthy individuals, were older, with delayed first marriage and first birth, and more abortions. Both demographic and reproductive factors correlated with Hr+BC and TNBC, with higher likelihood in postmenopausal, irregular menstruation, vaginal delivery, breastfeeding > 6 months, and hormonal contraceptive use. Reproductive factors associated with Hr+BC and TNBC risk were outlined. The adjusted model revealed delayed menarche increased Hr+BC risk by 1.71 times (OR 1.71, 95% CI 1.19-2.44) but decreased TNBC risk by 30% (OR 0.70, 95% CI 0.52-0.95). Longer time between first marriage and first birth (OR 1.40, CI 95% 1.10-1.78), irregular menstruation (OR 2.83, 95% CI 1.31-6.10), and hormonal contraceptive use (OR 5.68, 95%1.52-21.25) increased Hr+BC risk; pre-obesity decreased risk (OR 0.36 95% CI 0.18-0.72). Irregular menstruation (OR 4.30, 95% CI1.87-9.42) and hormonal contraceptive use (OR 8.54, 95% CI 1.81-40.14) increased TNBC risk. Higher abortions raised TNBC risk (OR 2.27, 95% CI 01.30-3.98) but not Hr+BC. Living in rural Bangladesh increased risk for both Hr+BC (4.81 times) and TNBC (16.77 times). Conclusions: Our findings highlight the significant impact of reproductive factors on Hr+BC and TNBC development in Bangladeshi women, emphasizing variations in risk profiles among different breast cancer types.

High-sensitive multi-cancers early detection for 8 cancer types by cell-free DNA targeted methylation sequencing: A retrospective cohort study.

3043 Background: Early screening effectively reduces mortality associated with cancer. Currently, most cancers lack effective screening paradigms. We developed blood-based multi-cancers early detection (MCED) and cancer signal origin (CSO) approaches in 8 types of cancers including esophageal, stomach, colorectal, pancreatic, liver, lung, breast and ovarian cancer. Methods: DNA methylation data generated based on GM-seq by public and internal whole genome methylation data. Based on these data, a panel of 155,362 CpG sites spanning the 2.0M genome was constructed and validated. We enrolled a case-control cohort of 746 participants (522 cancers, 224 non-cancers) for MCED model development. cell-free DNA (cfDNA) was isolated from 10 ml peripheral blood from each participant. A targeted methylation sequencing of cfDNA in plasma baseline was established using 224 non-cancers blood samples for 8 types of cancers. Finally, we developed a MCED model named AMBER for distinguishing cancer from non-cancer individuals. Results: DNA methylation data were from 8 types of cancers (cancer tissues: n=812, adjacent/normal tissues: n=416, cancer peripheral bloods: n=624, normal peripheral bloods: n=503) in internal and Infinium Human Methylation 450K array (cancer tissues: n=5000+, adjacent/normal tissues: n=1000+) from public data. 224 non-cancer individuals (healthy: n=196, cancer benign: n=28, male: female, 54.3%: 45.7%) were collected as control, while 522 cancer patients (male: female, 50.0%: 50.0%, stage I 26.9%, II 21.1%) from esophageal (n=56, stage I: n=10), stomach (n=47, stage I: n=11), colorectal (n=72, stage I: n=16), pancreatic (n=64, stage I: n=16), liver (n=69, stage I: n=22), lung (n=103, stage I: n=46), breast (n=41) and ovarian cancer (n=70, stage I: n=17). AMBER showed 99.1% specificity and total sensitivity 77.2% (95% confidence interval (CI): 73.4% to 80.7%). Of them, 56.8% (95% CI: 48.2% to 65.2%) of all stage I cases were detected, 70.6% (95% CI: 61.2% to 79.0%) for stage II, 84.5% (95% CI: 77.6% to 89.9%) for stage III, and 96.7% (95% CI: 91.8% to 99.1%) for stage IV. Strikingly, for stage I cancers, the sensitivity of esophageal, stomach, colorectal, pancreatic, liver, lung and ovarian cancer were 80.0%, 63.6%, 43.8%, 62.5%, 86.4%, 30.4% and 82.4% respectively. The sensitivity of esophageal, stomach, colorectal, pancreatic, liver, lung, breast and ovarian cancer reached 91.1%, 76.6%, 75.0%, 78.1%, 94.2%, 55.3%, 65.9% and 90.0%. For CSO model, the accuracy of TPO1 and TPO2 was 78.9% (95% CI: 74.6% to 82.8%) and 89.1% (95% CI: 85.6% to 92.0%). Conclusions: Our MCED tests demonstrated superior performance in detecting 8 types of cancers, especially early cancer screening, by utilizing cfDNA methylation information. It suggests the model can complement lack of multi-cancers early detection.

Assessment of plasma cell-free DNA fragmentation for multi-cancer early detection: An independent clinical validation study.

e15037 Background: Cell-free DNA (cfDNA) in the circulation has gained significant attention due to its potential applications for non-invasive early cancer detection. Fragmentomics of cfDNA is emerging as a promising field of biomarker research, exhibiting the capability to sensitively detect multiple cancer types. In previous retrospective research, we developed an approach called PatternWGS for comprehensive analysis of cfDNA fragmentation patterns and presented a multi-cancer detection model. In this study, we aim to evaluate the performance of PatternWGS in an independent validation cohort including lung, breast, colorectal, liver, and gastric cancers from a new clinical center. Methods: Participants with confirmed diagnosis of lung, breast, colorectal or liver cancer were enrolled in the cancer group. Non-cancer participants without known presence of malignancies were recruited from the same clinical center. Plasma samples from patients with lung (n=47), breast (n=19), colorectal (n=14), liver (n=8) and gastric (n=6) cancers, along with 101 non-cancer individuals were collected in this study. cfDNA was isolated from plasma and stored within a month prior to the whole genome sequencing. The characteristics of cfDNA fragmentation integrating fragment size profiles, motif patterns, genomic coverage distributions were utilized to evaluate the performance for cancer signal detection. In addition, the performance of estimated cfDNA tumor fraction, using copy number aberrations (ichorCNA), was compared with our approach. Results: 94 patients with one of five types of cancers and 101 non-cancer controls were prospectively enrolled between July 2023 and November 2023. Among the cancer group, 64% were at early stages (Stage I: 48%, Stage II: 16%). A significantly higher proportion of shorter fragments was observed in cancer group, and the degree increased with increasing cancer stage. Overall sensitivity across cancer types and stages was 72.3%, and the specificity for non-cancer controls was 80%. As expected, the sensitivity of cancer detection is higher in late-stage patients compared to those in the early-stages (61% in stage I, 80% in stage II, 84.6% in stage III, and 91.7% in stage IV). The sensitivity of detecting lung (72% had stage I cancer), breast, colorectal, liver, and gastric cancers reached 57.4%, 84.2%, 85.7%, 87.5% and 100% respectively. The detection performance using cfDNA tumor fraction by ichorCNA demonstrated a relatively low overall sensitivity of 28.7% (24.6% for stage I-II, 44% for stage III-IV). Conclusions: This independent clinical validation study, which focused on exploring plasma cfDNA fragmentation, demonstrated ideal performance in early-stage cancer detection. The cfDNA fragmentation-based approach exhibited a superior sensitivity in detecting early cancer signals compared with copy number aberrations-based approach.

Germline NPAT inactivating variants as cause of hereditary colorectal cancer.

Two independent exome sequencing initiatives aimed to identify new genes involved in the predisposition to nonpolyposis colorectal cancer led to the identification of heterozygous loss-of-function variants in NPAT, a gene that encodes a cyclin E/CDK2 effector required for S phase entry and a coactivator of histone transcription, in two families with multiple members affected with colorectal cancer. Enrichment of loss-of-function and predicted deleterious NPAT variants was identified in familial/early-onset colorectal cancer patients compared to non-cancer gnomAD individuals, further supporting the association with the disease. Previous studies in Drosophila models showed that NPAT abrogation results in chromosomal instability, increase of double strand breaks, and induction of tumour formation. In line with these results, colorectal cancers with NPAT somatic variants and no DNA repair defects have significantly higher aneuploidy levels than NPAT-wildtype colorectal cancers. In conclusion, our findings suggest that constitutional inactivating NPAT variants predispose to mismatch repair-proficient nonpolyposis colorectal cancer.

Metabolic Syndrome According to Dietary and Health-Related Lifestyle in Male Cancer Survivors and Non-Cancer over 40 Years of Age.

Researchers often report higher metabolic syndrome (MetS) pr\4;evalence among cancer survivors than among non-cancer individuals. This study aims to explore the impact of cancer presence, activity type, and dietary lifestyle on MetS in males over 40 years of age. Participants (n = 9846; 618 cancer survivors, 9228 non-cancer) were selected by extracting data from a Korean government database spanning the years 2016 to 2021. Physical activity patterns, dietary habits, and MetS factors were measured, and a multiple logistic regression analysis was statistically processed for an odds ratio (OR). MetS was present in 32.8% of cancer survivors and 28.6% of non-cancer individuals. Gastric cancer survivors exhibited a 16% lower OR for MetS versus non-cancer participants. The ORs were higher by 1.60-, 1.45-, and 1.26-fold for colorectal, urinary, and other cancers, respectively. Cancer survivors with high calorie, carbohydrate, and fat intakes exhibited ORs of 2.01 (95% CI 1.28-4.04), 2.33 (95% CI 1.28-4.54), and 1.39 (95% CI 1.05-2.37) compared to the recommended level. The high fiber-intake group reduced the MetS OR by 20%. In conclusion, The MetS prevalence was higher in survivors with colorectal cancer, urinary cancer, and other cancers, while it was lower in patients with gastric cancer. Survivors with low rates of eating three meals a day, high skipping breakfast, increased eating-out rate, and no nutritional learning opportunity displayed higher MetS prevalence. Additionally, cancer survivors who had more strength and leisure activities had a lower OR of MetS.

Abstract 1057: A blood-based multi-omics test for multicancer early detection: Combined retrospective and prospective studies

Abstract Background: Recent studies have demonstrated that blood-based multi-cancer early detection (MCED) approaches may hold promise for identifying asymptomatic cancer patients from general population. However, most studies only exploit a single aspect of cancer hallmarks, which is challenging for the biological reasons as cancer is a heterogenous disease with a wide spectrum of pathological and clinical behaviors. Here we report a multi-omics MCED assay named SeekInCare, a CE-IVD Mark blood test, which incorporates genomic hallmarks: copy number aberrations, fragment size, end motifs and oncogenic viruses via shallow whole genome sequencing from cfDNA, and seven plasma protein tumor markers in 8 ml blood. Methods: SeekInCare was developed using several retrospective cohorts and the method has been described in a publication (DOI: 10.1016/j.jmoldx.2021.06.003) IF: 4.1 Q2. Results: We present the validation in a retrospective cohort consisting of 584 non-cancer individuals and 617 cancer patients covering 27 cancer types. SeekInCare achieved 65.5% sensitivity at 97.9% specificity, resulting in an AUC of 0.936. The sensitivities were 46.9%, 60.0%, 68.9%, 81.8% in stage I, II, III, IV patients. The sensitivities of 10 common cancer types are as the following: breast (46.2%), stomach (46.4%), colorectum (56.5%), gallbladder (60.0%), lung (62.8%), pancreas (64.7%), lymphoma (68.5%), esophagus (70.0%), liver (77.5%), and leukemia (86.7%). These cancer types account for 73.5% of cancer incidence and 81.8% of cancer-related mortality in China. We prospectively evaluated SeekInCare in a real-world cohort consisting of 1203 individuals who received the test as a laboratory developed test (median follow-up time: 753 days) in which it achieved 60.0% sensitivity, 96.1% specificity, 11.5% PPV and 99.7% NPV. Conclusion: The performances of SeekInCare in both retrospective and prospective studies demonstrate that SeekInCare is an effective blood-based MCED test with similar performance as Grail’s Galleri test, which paves the way for clinical utility as a cancer screening test in average-risk populations. Citation Format: Mao Mao, Shiyong Li, Qingqi Ren, Yi Luan, Weijie Liang, Shuaipeng Geng, Dao-Ling Huang, Dandan Zhu, Yinyin Chang, Wei Wu, Yingying Zhang, Linfeng Zhang, Yan Wang, Yumin Feng, Bing Wei, Jie Ma, Chaohui Duan, Guanghui Long. A blood-based multi-omics test for multicancer early detection: Combined retrospective and prospective studies [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 1057.

Humoral and cellular immune responses against SARS-CoV-2 post-vaccination in immunocompetent and immunocompromised cancer populations.

The study was prompted by a desire to better assess the immune status of patients among our cancer host cohort, one of the largest in the New York metropolitan region. Hackensack Meridian Health is the largest healthcare system in New Jersey and cared for more than 75,000 coronavirus disease 2019 patients in its hospitals. The John Theurer Cancer Center sees more than 35,000 new cancer patients a year and performs more than 500 hematopoietic stem cell transplants. As a result, the work was undertaken to assess the effectiveness of vaccination in inducing humoral and cellular responses within this demographic.

Alterations in colorectal cancer virome and its persistence after surgery

Viruses are a key component of the colon microbiome, but the relationship between virome and colorectal cancer (CRC) remains poorly understood. We seek to identify alterations in the viral community that is characteristic of CRC and examine if they persist after surgery. Forty-nine fecal samples from 25 non-cancer (NC) individuals and 12 CRC patients, before and 6-months after surgery, were collected for metagenomic analysis. The fecal virome of CRC patients demonstrated an increased network connectivity as compared to NC individuals. Co-exclusion of influential viruses to bacterial species associated with healthy gut status was observed in CRC, suggesting an altered virome induced a change in the healthy gut bacteriome. Network analysis revealed lower connectivity within the virome and trans-kingdom interactions in NC. After surgery, the number of strong correlations decreased for trans-kingdom and within the bacteria and virome networks, indicating lower connectivity within the microbiome. Some co-occurrence patterns between dominant viruses and bacteria were also lost after surgery, suggesting a possible return to the healthy state of gut microbiome. Microbial signatures characteristic of CRC include an altered virome besides an altered bacterial composition. Elevated viral correlations and network connectivity were observed in CRC patients relative to healthy individuals, alongside distinct changes in the cross-kingdom correlation network unique to CRC patients. Some patterns of dysbiosis persist after surgery. Future studies should seek to verify if dysbiosis truly persists after surgery in a larger sample size with microbiome data collected at various time points after surgery to explore if there is field-change in the remaining colon, as well as to examine if persistent dysbiosis correlates with patient outcomes.

Evaluation of tumor-educated platelet long non-coding RNAs (lncRNAs) as potential diagnostic biomarkers for colorectal cancer.

Cancer-derived circulating components are increasingly considered as candidate sources for non-invasive diagnostic biomarkers. This study aimed to investigate the expression of tumor-educated platelet (TEP) long non-coding RNAs (lncRNAs) in colorectal cancer (CRC) patients and determine whether it could be served as a potential tool for CRC diagnosis. Relative quantitative real-time PCR (qRT-PCR) was used to detect the expression levels of three cancer-related platelet-derived lncRNAs CCAT1, HOTTIP, and XIST in 75 CRC patients and 42 healthy controls. Quantitative data were analyzed by SPSS (IBM Corp., Armonk, NY, USA) for comparison of cancer and non-cancer individuals. The receiver operating characteristic (ROC) curve analysis was further performed to assess the diagnostic values of lncRNAs within the CRC patients. The expression levels of lncRNAs colon cancer associated transcript 1 (CCAT1) ( P = 0.006) and HOXA transcript at the distal tip (HOTTIP) ( P = 0.049), but not X-inactive specific transcript (XIST) ( P = 0.12), were significantly upregulated in CRC patients compared to healthy individuals. However, there were no significant correlations between platelet lncRNAs and clinicopathological characteristics, including sex, age, tumor location, differentiation, and size (all at P > 0.05). The area under the ROC curve (AUC) of the lncRNA CCAT1 was 0.61 (sensitivity, 71%; specificity, 50%). TEP lncRNA CCAT1 is detectable in the circulation of CRC patients and could be considered as a potential diagnostic biomarker.

Synergistic Analysis of Lung Cancer's Impact on Cardiovascular Disease Using ML-Based Techniques.

Cancer patients are known to have a higher likelihood of developing Cardiovascular Disease (CVD) compared to non-cancer individuals. Although various types of cancer can contribute to the onset of CVD, lung cancer is inherently linked with increased susceptibility. To bridge this hypothesis, we propose a Lung cancer detection and Cardiovascular Disease Prediction (LCDP) system through lung Computed Tomography (CT) scan images. The lung cancer detection module of the LCDP system utilizes Transfer Learning (TL) with AdaDenseNet for classification. It employs the improvised Proximity-based Synthetic Minority Over-sampling Technique (Prox-SMOTE), improving accuracy. In the CVD prediction module, the feature extraction was performed using the VGG-16 model, followed by classification using a Support Vector Machine (SVM) classifier. The impact and interdependence of lung cancer on CVD were evident in our evaluation, with high accuracies of 98.28% for lung cancer detection and 91.62% for CVD prediction.

Metabolomic profile of neuroendocrine tumors identifies methionine, porphyrin, and tryptophan metabolisms as key dysregulated pathways associated with patient survival.

Metabolic profiling is a valuable tool to characterize tumor biology but remains largely unexplored in neuroendocrine tumors (NETs). Our aim was to comprehensively assess the metabolomic profile of NETs and identify novel prognostic biomarkers and dysregulated molecular pathways. Multiplatform untargeted metabolomic profiling (GC-MS, CE-MS, and LC-MS) was performed in plasma from 77 patients with G1-2 extra-pancreatic NETs enrolled in the AXINET trial (NCT01744249) (study cohort) and from 68 non-cancer individuals (control). The prognostic value of each differential metabolite (n = 155) in NET patients (P < .05) was analyzed by univariate and multivariate analyses adjusted for multiple testing and other confounding factors. Related pathways were explored by Metabolite Set Enrichment Analysis (MSEA) and Metabolite Pathway Analysis (MPA). Thirty-four metabolites were significantly associated with progression-free survival (PFS) (n = 16) and/or overall survival (OS) (n = 27). Thirteen metabolites remained significant independent prognostic factors in multivariate analysis, 3 of them with a significant impact on both PFS and OS. Unsupervised clustering of these 3 metabolites stratified patients in 3 distinct prognostic groups (1-year PFS of 71.1%, 47.7%, and 15.4% (P = .012); 5-year OS of 69.7%, 32.5%, and 27.7% (P = .003), respectively). The MSEA and MPA of the 13-metablolite signature identified methionine, porphyrin, and tryptophan metabolisms as the 3 most relevant dysregulated pathways associated with the prognosis of NETs. We identified a metabolomic signature that improves prognostic stratification of NET patients beyond classical prognostic factors for clinical decisions. The enriched metabolic pathways identified reveal novel tumor vulnerabilities that may foster the development of new therapeutic strategies for these patients.

Neuropsychiatric complications and associated management in adolescent and young adult cancer survivors: An All of Us study.

About 4.5% of new cancer cases affect adolescent and young adult aged between 15 and 39 years in the United States (US). However, the effect of neuropsychiatric conditions on long-term adolescent and young adult cancer (AYAC) survivors has not been formally investigated. Thus, the impact and management of late neuropsychiatric complications in AYAC survivors compared to non-cancer-matched controls (NCMC) in the US were evaluated using the All of Us (AoU) Research Program. Participants in the AoU Controlled Tier Dataset (v6) diagnosed with cancer between ages 15 and 39 were identified from electronic health records and surveys. AYAC survivors were matched with NCMC using the optimal pair-matching algorithm at a 1:4 ratio. Data on past diagnoses, current follow-up care, and treatment patterns of neuropsychiatric complications were collected. Analysis was performed on 788 AYAC survivors and 3152 NCMC. AYAC survivors, with an average of 8.8 years since their first cancer diagnosis, were more likely than NCMC to receive a diagnosis of neuropathy, memory loss and epilepsy (p < 0.001). Survivors also had a higher rate of follow-up care and treatment utilization for these neurological conditions compared to NCMC (p < 0.05). Treatment utilization was highest among survivors receiving care for epilepsy (88%), and lower for neuropathy (70%), memory loss (61%), and chronic fatigue (59%). This large study reveals that AYAC survivors, on average 9 years after their cancer diagnosis, require more frequent follow-up care for neurological complications compared to non-cancer individuals. However, the management of neuropathy, memory loss, and chronic fatigue is hindered by a lack of mechanism-based effective therapies.

Prevalence of Metabolic Syndrome Based on the Dietary Habits and Physical Activity of Korean Women Cancer Survivors.

Cancer is a major cause of death in Korea. Improving dietary habits and encouraging physical activity (PA) are important in managing the quality of life and health of patients. Cancer survivors (CS) often exhibit a higher incidence of metabolic syndrome (MetS) than non-cancer (NC) individuals. The purpose of this study was to analyze the prevalence of MetS according to dietary habits and PA in women who survived various cancers: stomach, colorectal, breast, cervical, lung, thyroid, and others. The participants (n = 12,676; NC: 11,673, CS: 1003) were analyzed cross-sectionally over a 6-year period. Caloric intake, eating-out frequency, breakfast frequency, dietary supplements, dietary therapy, nutritional education, participation in aerobic activity, strength training frequency, and sedentary lifestyle were evaluated. The prevalence of MetS was 1.22 (95% confidence interval (CI), 1.07-1.39) times higher in CS than in NC, exhibiting a 1.77-fold (95%CI, 1.14-2.74) increase in colorectal cancer, 1.72-fold (95%CI, 1.29-2.30) in cervical cancer, and 3.07-fold (95%CI, 1.14-5.31) in lung cancer. A higher-than-recommended caloric intake and frequent eating out increased MetS 1.43-fold (95%CI, 1.09-1.79) and 1.11-fold (95%CI, 1.01-1.64), respectively, in NC, and 1.31-fold (95%CI, 1.03-1.75) and 2.65-fold (95%CI, 2.29-3.07), respectively, in CS. Aerobic activity below the recommended level resulted in a 1.37-fold (95%CI, 1.13-1.71) and 1.36-fold (95%CI, 1.10-1.87) increase in NC and CS, respectively, whereas muscle strength increased 1.36-fold (95%CI, 1.08-1.70) and 1.49-fold (95%CI, 1.07-2.57), respectively, at below recommended levels. MetS was more prevalent in CS than in NC; high caloric intake, frequent eating out, low PA, and more sedentary time increased the risk of MetS.