Blood Tumor Markers Research Articles

Exploring clinical factors to predict the survival of patients with resectable non-small cell lung cancer with neoadjuvant immunotherapy.

The goal was to explore clinical factors and build a predictive model for the disease-free and overall survival of patients with non-small cell lung cancer (NSCLC) receiving neoadjuvant chemotherapy combined with immune checkpoint inhibitors. Inclusion criteria for patients in this multicentre study were as follows: (i) Patients who were diagnosed with stages I-III NSCLC after a bronchoscopy biopsy or puncture; (ii) patients who were examined with computed tomography/positron emission tomography-computed tomography before treatment and surgery; (iii) patients who received neoadjuvant chemotherapy combined with immune checkpoint inhibitors for 2 to 6 cycles preoperatively; (iv) patients whose peripheral blood indicators and tumour markers were assessed before treatment and preoperatively; (v) patients who underwent radical lung cancer surgery after neoadjuvant therapy. Cases were divided into high- and low-risk groups according to 78 clinical indicators based on a 10-fold Least Absolute Shrinkage and Selection Operator selection. We used Cox proportional hazards models to predict disease-free and overall survival. Then, we used time-dependent area under the curve and decision curve analyses to examine the accuracy of the results. Data were collected continuously, and 212 and 85 cases were randomly assigned to training and testing sets, respectively. The area under the curve for the prediction of disease-free survival (training: 1 year, 0.83; 2 years, 0.81; 3 years, 0.83 versus testing: 1 year, 0.65; 2 years, 0.66; 3 years, 0.70), overall survival (training: 1 year, 0.86; 2 years, 0.85; 3 years, 0.86 versus testing: 1 year, 0.66; 2 years, 0.57; 3 years, 0.70) were determined. The coefficient factors including pathological response; preoperative tumour maximum diameter; preoperative lymph shorter diameter; preoperative tumour and lymph maximum standardized uptake value; change in tumour standardized uptake value preoperatively; and blood-related risk factors were favourably associated with prognosis (P < 0.001). Our prediction model, which integrated data from preoperative positron emission tomography-CT, preoperative blood parameters and pathological response, was able to make highly accurate predictions for disease-free and overall survival in patients with NSCLC receiving neoadjuvant immunity with chemical therapy.

Prediction of ovarian cancer using artificial intelligence tools.

Ovarian cancer is a common type of cancer and a leading cause of death in women. Therefore, accurate and fast prediction of ovarian tumors is crucial. One of the appropriate and precise methods for predicting and diagnosing this cancer is to build a model based on artificial intelligence methods. These methods provide a tool for predicting ovarian cancer according to the characteristics and conditions of each person. In this study, a data set included records related to 171 cases of benign ovarian tumors, and 178 records related to cases of ovarian cancer were analyzed. The data set contains the records of blood test results and tumor markers of the patients. After data preprocessing, including removing outliers and replacing missing values, the weight of the effective factors was determined using information gain indices and the Gini index. In the next step, predictive models were created using random forest (RF), support vector machine (SVM), decision trees (DT), and artificial neural network (ANN) models. The performance of these models was evaluated using the 10-fold cross-validation method using the indicators of specificity, sensitivity, accuracy, and the area under the receiver operating characteristic curve. Finally, by comparing the performance of the models, the best predictive model of ovarian cancer was selected. The most important predictive factors were HE4, CA125, and NEU. The RF model was identified as the best predictive model, with an accuracy of more than 86%. The predictive accuracy of DT, SVM, and ANN models was estimated as 82.91%, 85.25%, and 79.35%, respectively. Various artificial intelligence (AI) tools can be used with high accuracy and sensitivity in predicting ovarian cancer. Therefore, the use of these tools can help specialists and patients with early, easier, and less expensive diagnosis of ovarian cancer. Future studies can leverage AI to integrate image data with serum biomarkers, thereby facilitating the creation of novel models and advancing the diagnosis and treatment of ovarian cancer.

Comparison of the diagnostic value of various microRNAs in blood for colorectal cancer: a systematic review and network meta-analysis

BackgroundDespite the existence of numerous studies investigating the diagnostic potential of blood microRNAs for colorectal cancer, the microRNAs under consideration vary widely, and comparative analysis of their diagnostic value is lacking. Consequently, this systematic review aims to identify the most effective microRNA blood tumor markers to enhance clinical decision-making in colorectal cancer screening.MethodA comprehensive search of databases, including PubMed, Embase, Web of Science, Scopus, and Cochrane, was conducted to identify case‒control or cohort studies that examined the diagnostic value of peripheral blood microRNAs in colorectal cancer. Studies were included if they provided sensitivity and specificity data, were published in English and were available between January 1, 2000, and February 10, 2023. The Critical Appraisal Skills Programme (CASP) checklist was employed for quality assessment. A Bayesian network meta-analysis was performed to estimate combined risk ratios (RRs) and 95% confidence intervals (CIs), with results presented via rankograms. This study is registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), 202,380,092.ResultsFrom an initial pool of 2254 records, 79 met the inclusion criteria, encompassing a total of 90 microRNAs. The seven most frequently studied microRNAs (43 records) were selected for inclusion, all of which demonstrated moderate to high quality. miR-23, miR-92, and miR-21 exhibited the highest sensitivity and accuracy, outperforming traditional tumor markers CA19-9 and CEA in terms of RR values and 95% CI for both sensitivity and accuracy. With the exception of miR-17, no significant difference was observed between each microRNA and CA19-9 and CEA in terms of specificity.ConclusionsAmong the most extensively researched blood microRNAs, miR-23, miR-92, and miR-21 demonstrated superior diagnostic value for colorectal cancer due to their exceptional sensitivity and accuracy. This systematic review and network meta-analysis may serve as a valuable reference for the clinical selection of microRNAs as tumor biomarkers.

Tumour-specific activation of a tumour-blood transport improves the diagnostic accuracy of blood tumour markers in mice

The accuracy of blood-based early tumour recognition is compromised by signal production at non-tumoral sites, low amount of signal produced by small tumours, and variable tumour production. Here we examined whether tumour-specific enhancement of vascular permeability by the particular tumour homing peptide, iRGD, which carries dual function of binding to integrin receptors overexpressed in the tumour vasculature and is known to promote extravasation via neuropilin-1 receptor upon site-specific cleavage, might be useful to improve blood-based tumour detection by inducing a yet unrecognised vice versa tumour-to-blood transport. To detect an iRGD-induced tumour-to-blood transport, we examined the effect of intravenously injected iRGD on blood levels of α-fetoprotein (AFP) and autotaxin in several mouse models of hepatocellular carcinoma (HCC) or in mice with chronic liver injury without HCC, and on prostate-specific antigen (PSA) levels in mice with prostate cancer. Intravenously injected iRGD rapidly and robustly elevated the blood levels of AFP in several mouse models of HCC, but not in mice with chronic liver injury. The effect was primarily seen in mice with small tumours and normal basal blood AFP levels, was attenuated by an anti-neuropilin-1 antibody, and depended on the concentration gradient between tumour and blood. iRGD treatment was also able to increase blood levels of autotaxin in HCC mice, and of PSA in mice with prostate cancer. We conclude that iRGD induces a tumour-to-blood transport in a tumour-specific fashion that has potential of improving diagnosis of early stage cancer. Deutsche Krebshilfe, DKTK, LOEWE-Frankfurt Cancer Institute.

Supersulfide metabolome of exhaled breath condensate for diagnostic biomarkers of esophageal cancer.

e15027 Background: The early estimate and detection of esophageal cancer (EC) is essentially required for continuous esophagogastroduodenoscopy and histopathological diagnosis. However, endoscopic examination is sometimes invasive, which may cause somehow limited clinical application and compliance. Also, the traditional blood tumor marker is unsuitable for a cancer screening. In recent years, the energy production by sulfur respiration in hypoxic environments in cancer tissues is getting spotlighted in tumor biology. The current study is aimed to evaluate usefulness of sulfur containing compounds as new biomarkers for EC by using blood samples and exhaled breath condensate (EBC) that can be readily obtained in a non-invasive fashion. Methods: Fifty EC patients were included in the study between June 2021 and September 2021. EBC and plasma samples were collected before starting any medicinal remedy including medication, chemotherapy, radiation, surgery, and endoscopic and dentistry maneuvers. Thirty healthy controls were recruited if they did not have any cancer history, surgery and aged over 50s preferred age for esophageal cancer. All samples were stored at -80℃ immediately after appropriate preparation until the following inspection. Then, sulfur metabolome analysis using LC-MS/MS was performed to see the difference of metabolic profile between the two groups. We used Student t tests for comparing two groups, and one -way ANOVA test for more than two groups, with significance set at P&lt;0.05. To evaluate the diagnostic value of some metabolites, ROC curves and the AUC were calculated. Results: The supersulfide metabolic profiles were remarkably different between EC patients and controls. Especially, cysteine persulfide (CysSSH) was significantly increased in both EBC and plasma of the EC patients. The sensitivity and specificity of CysSSH in EBC were 60% and 96%, respectively, with an AUC of 0.71. The sensitivity and specificity of CysSSH in plasma were 49% and 96%, respectively, with an AUC of 0.73. In addition, homocysteine persulfide (HomoCysSSH) in plasma showed more significant difference than CysSSH and was able to distinguish EC patients from healthy subjects with AUC of 0.93 (sensitivity, 89%; specificity, 96%). The level of HomoCysSSH was correlated with that of CysSSH in EBC. The subgroup analysis for histological subtypes and tumor progression showed that both two metabolites were increased in EC patients regardless of histological type and disease’ progression. In particular, the amount of homoCysSSH in plasma was statistically higher in early-stage EC than that of controls (p&lt;0.0001). Conclusions: Supersulfides like CysSSH and HomoCysSSH could be potential biomarkers for detecting EC. Cysteine persulfide from EBC may serve as a valuable non-invasive biomarker with similar detectable ability compared with several biomarkers of blood samples that are currently reported.

Abstract PO3-05-12: Randomized Phase 2 of Bria-IMT, an Allogenic Human Cell Line with Antigen Presenting Activity, in Heavily Pretreated Metastatic Breast Cancer

Abstract Introduction Despite progress in MBC, too many continue to succumb due to treatment resistance or intolerance. SV-BR-1-GM is an allogenic human breast cancer cell line with antigen presenting cell activity designed to overcome the immune-suppressive tumor microenvironment while being acceptable to extensively pretreated contemporary MBC patients. We report interim exploratory analysis of the ongoing RCT of the Bria-IMT regimens. Methods An interim exploratory analysis using preliminary partially available evaluable data of the ongoing prospective, randomized phase 2 (NCT03328026; 2018-present) of Bria-IMT (irradiated SV-BR-1-GM) with a PD-1check point inhibitor (CPI) every 3 weeks (25 patients dosed to date). Both regimens include cyclophosphamide 300 mg/m2 48-72 hours prior to intradermal Bria-IMT (~20 x 106 cells) followed by interferon-alpha at the inoculation sites 2 days later. The control arm used the original sequence with simultaneous start of Bria-IMT and CPI in cycle 1. The experimental arm started CPI in cycle 2 after the 2nd inoculation. Candida skin test was performed before cycle 1 to determine anergy status while delayed-type hypersensitivity skin test (DTH), defined as &amp;gt;5mm erythema &amp; induration, was done at every cycle by intradermal injection of a small test dose of Bria-IMT prior to full dose inoculation. Results Median age: 58 (range 37-81); median prior therapies: 8 lines (range 4-18); 89% were grade 2/3 (n=18); 68% hormone receptor positive; 61% HER2 negative, 33% HER2 low, and 6% HER2 high; 33% triple negative. Overall, 53% of subjects had a clinical benefit as best response by BICR, PI or target lesion measurement. The two treatment arms were similar with a trend showing longer median durations on therapy (mDOT) of 3.7 mo in the experimental delayed CPI arm compared with mDOT = 2.9 for original sequence control arm. 47% of patients were anergic to candida. Among all anergic subjects, the mDOT was 3.5 compared to 2.5 mo for non-anergic patients. However, among anergic subjects, the alternative treatment arm had a lower risk of treatment discontinuation (improved HR) with mDOT of 3.7 compared to the 3.3 mo mDOT of the original treatment. 50% of anergic subjects eventually developed DTH to SV-BR-1-GM. mDOT was 4.0 mo for DTH+ pts vs 3.0 mo for those who did not mount DTH. Median OS was not yet reached; mean OS was higher in non-anergic vs anergic pts. Among those who developed an inoculation site reaction to Bria-IMT, OS was greater than for those who did not. Time on the Bria-IMT regimen exceeded the time on penultimate treatment in 22% of subjects while 33% of subjects with prior CPI use exceeded last therapy. AEs were mild with 28% of subjects (n=7) having &amp;gt; grade 3 events. The most common grade 3+ AE was lipase increase (n=3). One subject with encouraging changes in peripheral blood tumor markers and CTCs completed a PET study using Zr-89 crefmirlimab berdoxam, a zirconium-89 labelled truncated antibody specific to human CD8α (CD8 Immuno-PET) and demonstrated increased uptake in some metastatic lesions and draining lymph nodes. Updated results will be provided at the meeting. Conclusion Sequencing of CPI with Bria-IMT is associated with differential clinical outcome trends but not statistically significant in this interim preliminary exploratory analysis regardless of prior CPI use. Bria-IMT is immunogenic with clinical benefit demonstrated for both treatment schedules among patients with inducible DTH reactions. Patients who develop an immune response to Bria-IMT had an increase in OS compared to those who did not. The nodal localization of CD8+ cells on PET may indicate a systemic activation of CD8 positive lymphoid cells. It also provides support that the Bria-IMT + CPI combination immune-based therapy can result in an increase of CD8+ tumor infiltrating lymphocytes in breast cancer metastatic sites. These preliminary results will be evaluated in the ongoing randomized phase 3 pivotal registrational trial. Citation Format: Carmen Calfa, Chaitali Nangia, Minal Barve, John Knecht, Jarrod Holmes, Kendrith Roland, Ralph Boccia, Frances Valdes-Albini, Zach Gostout, Mingjin Chang, William Williams, Charles Wiseman, Bonnie Guerin, Shaker Dakhil, Giuseppe Del Priore, Saranya Chumsri. Randomized Phase 2 of Bria-IMT, an Allogenic Human Cell Line with Antigen Presenting Activity, in Heavily Pretreated Metastatic Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-05-12.

Abstract PO1-20-12: CD8+ Tumor Infiltrating Lymphocytes Turn a Cold Tumor Hot in Metastatic Breast Cancer

Abstract Introduction: Turning “cold” tumors “hot” is considered essential for immune-oncology therapies to be effective. Bria-IMT is an allogenic human cancer cell line with antigen presenting cell activity (SV-BR-1-GM) designed to overcome the immune-suppressive tumor microenvironment. However, until now there has not been proof that “cold” tumors can become “hot” with this therapy. Using Zr-89 crefmirlimab berdoxam, a zirconium-89 labelled truncated antibody specific to human CD8α and developed for CD8 ImmunoPET, we image before and after Bria-IMT therapy administration to assess the baseline status as well as changes in CD8 cell presence after initiation of therapy. Here we present the first evidence that cold tumors can become hot on treatment with Bria-IMT combined with an anti-PD-1 checkpoint inhibitor (CPI), showing CD8+ cells increased over baseline using CD8 ImmunoPET. Case: After informed consent, a 61 year-old Hispanic female, enrolled in the ongoing randomized phase 2 Bria-IMT trial in advanced heavily pretreated metastatic breast cancer (MBC) (NCT03328026). Her history included MBC in May 2020, ductal type, grade 3, triple negative breast cancer (TNBC) with 6 prior lines of therapy including a Trop-2-directed antibody-drug conjugate and 6 lines of chemotherapy. Precision medicine testing identified no actionable targets. All prior therapies had progressive disease as their best response. The subject was randomized to start the CPI after 2 cycles of Bria-IMT to “train” the host immune system before proceeding with combination immune-oncology therapy. Baseline testing revealed the subject to be anergic to candida and SV-BR-1-GM inoculation. However, by cycle 3 delayed-type hypersensitivity to SV-BR-1GM developed. Interestingly the subject matched SV-BR-1-GM at 2 HLA loci: DRB3*02:02 and DRB1*11:04 which in previous publications is associated with greater clinical benefit. Tumor markers were stable or decreased slightly including CEA (25% decrease) and CA 15-3 (43% decrease). Circulating Tumor Cells (CTCs) and Cancer Associated Macrophage Like cells (CAMLs) also improved. Standard imaging at baseline showed 3 main sites of disease including a large right breast mass, multiple right axillary lymph nodes and a right lower lobe mass with CD8 ImmunoPET uptake in these areas similar to the blood pool. On the follow-up CT imaging, all of these lesions increased in size with newly appreciated pulmonary nodules. The right lower lobe mass showed increased CD8 ImmunoPET accumulation with an SUV of 5.8 (close to the liver background) as compared to an SUV of 2.2 at baseline. The lesions in the right breast and right axilla remained at blood pool levels. There was an increase in CD8 ImmunoPET uptake in bilateral inguinal lymph nodes reaching an SUV of 4.8 as compared to SUV 2.2 at baseline. In addition, there were non-enlarged lymph nodes in bilateral axillary regions that also showed increased radio-tracer accumulation reaching an SUV of 9.5 as compared to SUV 4.9 at baseline. Conclusion: This subject demonstrated a mixed response of metastatic lesions on CD8 ImmunoPET with encouraging changes in peripheral blood tumor markers and CTCs. The nonspecific nodal localization of CD8 ImmunoPET may indicate a systemic activation of CD8 positive lymphoid cells. This shows the value of CD8 ImmunoPET in identifying lesions that are progressing on treatment versus pseudo progression. It also provides support that the Bria-IMT + CPI combination immune-based therapy can result in an increase of CD8+ tumor infiltrating lymphocytes in breast cancer metastatic sites as well as an increase in lymphoid organs. This advance may aid in triaging patients, adjudicating pseudo-progression and predicting clinical benefit of immune based therapies. Citation Format: Russ Kuker, Frances Valdes-Albini, Giuseppe Del Priore, Aazim Arif, Kristin Schmiedehausen, Carmen Calfa. CD8+ Tumor Infiltrating Lymphocytes Turn a Cold Tumor Hot in Metastatic Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-20-12.

Plasma-based lipidomics reveals potential diagnostic biomarkers for esophageal squamous cell carcinoma: a retrospective study.

Esophageal squamous cell carcinoma (ESCC) is highly prevalent and has a high mortality rate. Traditional diagnostic methods, such as imaging examinations and blood tumor marker tests, are not effective in accurately diagnosing ESCC due to their low sensitivity and specificity. Esophageal endoscopic biopsy, which is considered as the gold standard, is not suitable for screening due to its invasiveness and high cost. Therefore, this study aimed to develop a convenient and low-cost diagnostic method for ESCC using plasma-based lipidomics analysis combined with machine learning (ML) algorithms. Plasma samples from a total of 40 ESCC patients and 31 healthy controls were used for lipidomics study. Untargeted lipidomics analysis was conducted through liquid chromatography-mass spectrometry (LC-MS) analysis. Differentially expressed lipid features were filtered based on multivariate and univariate analysis, and lipid annotation was performed using MS-DIAL software. A total of 99 differential lipids were identified, with 15 up-regulated lipids and 84 down-regulated lipids, suggesting their potential as diagnostic targets for ESCC. In the single-lipid plasma-based diagnostic model, nine specific lipids (FA 15:4, FA 27:1, FA 28:7, FA 28:0, FA 36:0, FA 39:0, FA 42:0, FA 44:0, and DG 37:7) exhibited excellent diagnostic performance, with an area under the curve (AUC) exceeding 0.99. Furthermore, multiple lipid-based ML models also demonstrated comparable diagnostic ability for ESCC. These findings indicate plasma lipids as a promising diagnostic approach for ESCC.

Relevance of blood tumor markers in inpatients with significant involuntary weight loss and elevated levels of inflammation biomarkers

PurposeTo assess the diagnostic performance of a panel of standard tumor markers (TMs) in patients hospitalized with significant involuntary weight loss (IWL) and elevated levels of inflammation biomarkers, and a combination of the TM panel and the finding of the computed tomography (CT) scan.MethodsWe conducted a retrospective study in the internal medicine department at Amiens-Picardie University Medical Center (Amiens, France) between January 1st, 2015, and November 1st, 2021. The inclusion criteria were age 18 or over, significant IWL (≥ 5 kg over 6 months), elevated inflammation biomarkers (e.g. C-reactive protein), and assay data on two or more standard TMs (carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19 − 9, CA 15 − 3, CA 125, neuron-specific enolase (NSE), alpha-fetoprotein (AFP), calcitonin, and prostate-specific antigen (PSA)). The result of each TM assay was interpreted qualitatively (as positive or negative), according to our central laboratory’s usual thresholds.ResultsCancer was diagnosed in 50 (37.0%) of the 135 patients included. Positivity for one or more TMs had a positive predictive value (PPV) of 0.55 [0.43–0.66], and a negative predictive value (NPV) of 0.84 [0.75–0.93] for cancer diagnosis. When combined with the presence of suspicious CT findings (e.g. a mass, enlarged lymph nodes and/or effusion), positivity for one or more TMs had a PPV of 0.92 [0.08–0.30]. In the absence of suspicious CT findings, a fully negative TM panel had an NPV of 0.96 [0.89-1.00].ConclusionA negative TM panel argues against the presence of a cancer, especially in the absence of suspicious CT findings.

Abstract 3658: Longitudinal tumor-informed ctDNA monitoring with the originally developed OTS-Assay system

Abstract Background: Cancer Genome Profiling (CGP) tests are now widely available in daily practice. However, only a very small fraction of patients have the opportunity for genome-guided therapies. Somatic mutations from cancer specimens are unique to individual patients and hold utility as individual tumor markers in blood. We have developed an original circulating tumor DNA (ctDNA) monitoring system, called OTS (Off-The-Shelf)-Assay, at Iwate Medical University Hospital, Yahaba, Japan. Patients and Methods: Between April 2022 and October 2023, 79 patients who received the OTS-Assay were enrolled in the present analysis. The OTS-Assay includes three steps: (a) OTS-Scan (somatic mutation identification by either tissue or blood), (b) OTS-Select (somatic mutation selection), and (c) OTS-Monitor (periodical somatic mutation quantification as ctDNA). For the OTS-Select, we established an originally developed &amp;gt;90 stepwise selection algorithm. One of the determinants is the availability of appropriate digital PCR (dPCR) probes for individual patients. Here, we search the probes for individual patients from the dPCR probe library, OTS-1000ex, which consists of &amp;gt;1000 probes against frequently reported human somatic mutations (Quantdetect, Tokyo, Japan). Results: All 79 patients were subject to the analysis. The cancer stage of all the patients was advanced. More than 10 tumor types were enrolled, including esophagus (n=42), colorectal (n=12), breast (n=7), lung (n=4), pancreas (n=3), hematological (n=3), and others (n=8). Fifty patients received OTS-Scan, and 29 patients had received a CGP test before the OTS-Assay (i.e., OTS-Scan was not needed). Seventy-five patients received OTS-Select, meaning that four patients had somatic mutations that were designated for ctDNA monitoring. All 79 patients received at least one OTS-monitor. The number of OTS-Monitors received ranged from 1 to 11 during the 19-month period, and the average interval was 3.0 months. The average pretreatment variant allele frequency (VAF) was 4.96% and the majority of the follow-up VAF was less than 1%. More than 90% of the patients had at least one clinical validity defined by: (a) early relapse prediction, (b) treatment efficacy evaluation, or (c) no relapse corroboration. Conclusion: The OTS-Assay system provides stable longitudinal ctDNA monitoring at the range of less than 1% of VAF using the originally developed dPCR probe library. The sensitivity and affordability of the OTS-Assay system allows frequent monitoring, which leads to obtaining important clinical information in the context of advanced cancer therapy. Citation Format: Satoshi S. Nishizuka, Hayato Hiraki, Akiko Yashima-Abo, Takeshi Iwaya. Longitudinal tumor-informed ctDNA monitoring with the originally developed OTS-Assay system [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 3658.

Correlation analysis of urinary arsenic species and health effect indicators of occupational arsenic exposure workers

Objective: To explore the correlation between urinary arsenic and health effects through the determination and analysis of urinary arsenic levels in occupational arsenic exposed workers. Methods: In November 2021, 95 workers exposed to arsenic and its inorganic compounds and 31 administrative personnel from a non-ferrous metal smelter in Yunnan Province were selected as the contact group and control group, respectively. Urine forms of arsenic, blood tumor markers, liver function were detected, and micronucleus test was used to analyze the chromosome damage. The correlation between urine forms of arsenic and health effects were analyzed. Results: Compared with the control group, the concentrations of urinary trivalent inorganic arsenic (iAs(3+)) , pentavalent inorganic arsenic (iAs(5+)) , inorganic arsenic (iAs=ΣiAs(3+)+iAs(5+)) , monomethyl arsenic (MMA) , dimethyl arsenic (DMA) and urinary arsenic (ΣiAs+MMA+DMA) at the end of class in contact group were higher (P<0.05) . There was no statistically significant difference in blood tumor markers and liver function indicators between the two groups (P>0.05) . Compared with the control group, the peripheral blood micronucleus rate and cell micronucleus rate in the contact group were significantly increased (P<0.05) . The urinary arsenic, iAs(5+), inorganic arsenic and DMA were positively correlated with peripheral blood micronucleus rate in contact group (r(s)=0.48, 0.34, 0.37, 0.23, P<0.05) , and the urinary arsenic, iAs(5+), DMA were positively correlated with peripheral blood micronucleus rate (r(s)=0.48, 0.34, 0.26, P<0.05) . Conclusion: There is a significant correlation between different valence states of arsenic in the urine and abnormal health effects of occupational arsenic exposed workers. It is necessary to strengthen the detection of arsenic species in the urine of occupational arsenic exposed workers to better protect their health.

PEDIATRIK PINEAL VE TEKTAL BÖLGE TÜMÖRLERI: Nöroendoskopi kullanımı

Purpose: In this article, we aimed to contribute to the literature by describing our approach to pediatric pineal and tectal masses treated with endoscopic interventions in our clinic.&#x0D; Materials and methods: We retrospectively reviewed the records of 26 patients with lesions in the pineal and tectal regions who underwent endoscopic procedures between 2012 and 2023 at Gazi University Department of Pediatric Neurosurgery. Demographic data, blood tumor markers (alpha fetoprotein-BETA AFP, alpha fetoprotein-β-hCG), pathological diagnoses, reasons for clinical presentation, presence of hydrocephalus and additional interventions were analyzed. &#x0D; Results: Of the 26 patients who underwent endoscopic procedure, 6 had lesions in the pineal region and 20 had lesions in the tectal region. The success rate for ETV was 75-80%. The success rate for ETV was 78.3% for patients with tumors in the pineal region and 84% for tectal tumors.&#x0D; Conclusion: Pineal or tectal region tumors are a rare group of tumors. In addition, these regions are among the most heterogeneous regions in the central nervous system in terms of tumor type and histology. Endoscopic intervention through a single burr hole using rigid endoscopy is a comfortable and safe minimally invasive method for both pathologic sampling and management of hydrocephalus in indicated cases in the same session.

Construction and Validation of a Gastric Cancer Diagnostic Model based on Blood Groups and Tumor Markers.

Objective: The aim of this study is to explore the value of combined detection of ABO blood group and tumor markers in the diagnosis of gastric cancer. Methods: A total of 3650 gastric cancer patients treated in our center from January 2015 to December 2019, and 5822 controls were recruited, and divided into training set and validation set according to 7:3. The diagnostic and predictive model of gastric cancer was constructed by binary logistic regression method in the training set. The diagnostic value of the prediction model for gastric cancer was evaluated by calculating the prediction probability P value and drawing the Receiver operating characteristic (ROC) curve, and was verified in the validation set. Results: The Area under the curve (AUC) of the diagnosis and prediction model in the training set was 0.936 (95%CI: 0.926-0.941), the sensitivity was 81.66%, and the specificity was 98.61%. In the validation set, the AUC was 0.941 (95%CI: 0.932-0.950), the sensitivity was 82.33%, and the specificity was 99.02%. Furthermore, the diagnostic model obtained in this study had a high diagnostic value for early gastric cancer patients in the healthy population (AUC of training set, validation set and total population were 0.906, 0.920 and 0.908, respectively). Conclusions: We constructed a diagnostic model for gastric cancer including blood group and tumor markers, which has high reference value for the diagnosis of gastric cancer patients, and the model can better distinguish early gastric cancer from healthy people.

Ternary electrochemiluminescence quenching effects of CuFe2O4@PDA-MB towards self-enhanced Ru(dcbpy)32+ functionalized 2D metal-organic layer and application in carcinoembryonic antigen immunosensing

BackgroundCarcinoembryonic antigen (CEA) is a significant glycosylated protein, and the unusual expression of CEA in human serum is used as a tumor marker in the clinical diagnosis of many cancers. Although scientists have reported many ways to detect CEA in recent years, such as electrochemistry, photoelectrochemistry, and fluorescence, their operation is complex and sensitivity is average. Therefore, finding a convenient method to accurately detect CEA is significance for the prevention of malignant tumors. With high sensitivity, quick reaction, and low background, electrochemiluminescence (ECL) has emerged as an essential method for the detection of tumor markers in blood. ResultsIn this work, a “signal on-off” ECL immunosensor for sensitive analysis of CEA ground on the ternary extinction effects of CuFe2O4@PDA-MB towards a self-enhanced Ru(dcbpy)32+ functionalized metal-organic layer [(Hf)MOL-Ru-PEI-Pd] was prepared. The high ECL efficiency of (Hf)MOL-Ru-PEI-Pd originated from the dual intramolecular self-catalysis, including intramolecular co-reaction between polyethylenimine (PEI) and Ru(dcbpy)32+. At the same time, loading Pd NPs onto (Hf)MOL-Ru-PEI could not only improve the electron transfer ability of (Hf)MOL-Ru-PEI, but also provide more active sites for the reaction of Ru(dcbpy)32+ and PEI. In the presence of CEA, CuFe2O4@PDA-MB-Ab2 efficiently quenches the excited states of (Hf)MOL-Ru-PEI-Pd by PDA, Cu2+, and methylene blue (MB) via energy and electron transfer, leading to an ECL signal decrease. Under optimal conditions, the proposed CEA sensing strategy showed satisfactory properties ranging from 0.1 pg mL−1 to 100 ng mL−1 with a detection limit of 20 fg mL−1. SignificanceThe (Hf)MOL-Ru-PEI-Pd and CuFe2O4@PDA-MB were prepared in this work might open up innovative directions to synthesize luminescence-functionalized MOLs and effective quencher. Besides, the ECL quenching mechanism of Ru(dcbpy)32+ by MB was successfully explained by the inner filter effect (ECL-IFE). At last, the proposed immunosensor exhibits excellent repeatability, stability, and selectivity, and may provide an attractive way for CEA and other disease markers determination.

Evaluating the Efficacy of Fecal Occult Blood Test and Tumor Marker Combined Screening for Colorectal Cancer

Objective: To analyze the screening effectiveness of combining the fecal occult blood test with tumor marker detection for colorectal cancer. Methods: A total of thirty patients with colorectal cancer and thirty patients with benign colon hyperplasia who received treatment from January 2020 to January 2023 were selected. These patients were assigned to the observation group and the control group, respectively. All patients in both groups underwent both fecal occult blood tests and tumor marker detection. The levels of tumor markers between the two groups were compared, the tumor marker levels in different stages were assessed within the observation group, and the positive detection rates for single detection and combined detection were compared. Results: The levels of various tumor markers in the observation group were significantly higher than those in the control group (P &lt; 0.05). Furthermore, as the Duke stage increased within the observation group, the levels of various tumor markers also increased (P &lt; 0.05). The positive detection rate of the combined test was notably higher than that of single detection (P &lt; 0.05). Conclusion: Combining the fecal occult blood test with tumor marker detection in colorectal cancer screening can significantly improve the overall detection rate.

Clinical significance of serum synaptophysin-like 1 protein levels in breast cancer.

Mammography, used for breast cancer (BC) screening, has limitations such as decreased sensitivity in dense breasts. Currently used tumor markers are insufficient in diagnosing breast cancer. In this study, we aimed to investigate the relationship between serum levels of synaptophysin-like protein 1 (SYPL1) and BC and compare SYPL1 with other blood tumor markers. The study group consisted of 80 female patients with a histopathological diagnosis of invasive BC who received no radiotherapy/chemotherapy. The control group was 72 women with no previous history of breast disease and evaluated as Breast Imaging Reporting and Data Systems (BI-RADS 1-2) on imaging. Serum SYPL1, cancer antigen 15-3 (CA 15-3), and carcinoembryonic antigen (CEA) were measured in both groups.

Predictive value of circulating tumor cell counts during the treatment of cancer: interactions with the blood microenvironment.

This study aimed to evaluate the prognostic value of circulating tumor cell (CTC) in tumor patients during treatment. This study retrospectively analyzed clinical data obtained from 174 cancer patients during treatment. The relationship between the CTC counts and clinicopathological variables was analyzed. A ROC curve was applied to determine the optimal cut-off values and assess the predictive ability of the prognostic indicators. The overall survival (OS) for different prognostic factors was calculated using the Kaplan-Meier method, and the difference between the survival curves was then compared using the log-rank test. Cox regression model was used to investigate the effect of independent factors on patients' survival. The CTC-positive rate was positively correlated with the clinicopathological variables of TNM stage, tumordifferentiation, serum CEA level, and ki-67%. In the differential analysis of hematological microenvironment parameters in CTC-positive and CTC-negative samples, the complete blood count, blood biological chemistry, tumor markers (CEA, CA19-9, CA72-4), and lymphocyte subpopulation were statistically significant. The results of the ROC curve analysis indicated that the serum CEA level was the best diagnostic indicator to discriminate the CTC count in tumor patients. Additionally, the results of the univariate and multivariate analyses of OS in relation to clinical variables revealed that the CTC counts were an independent prognostic factor for unfavorable OS. The CTC counts in patients with tumors undergoing treatment were significantly correlated with hematological microenvironment parameters. The detection of CTCs may therefore be used as an indicator of tumor prognosis.

Combined measurement of circulating tumor cells and magnetic nanoparticles-assisted multiple blood markers improves the diagnostic efficiency of early-stage lung adenocarcinoma

The study aims to evaluate the efficiency and clinical value of circulating tumor cells (CTCs), blood tumor markers, and serum microRNAs for diagnosing lung adenocarcinoma in its early stages. The study included 40 patients with early-stage lung adenocarcinoma, 40 individuals with benign pulmonary nodules, and 40 healthy volunteers in groups 1, 2, and 3, respectively. The negative enrichment–fluorescence in situ hybridization was used to classify and quantify the aneuploidy and its number distribution in CTCs in groups 1–3. Magnetic nanoparticles were used to extract DNA. The levels of miR-223-3p and miR-486-5p in the serum of groups 1–3 were then determined using reverse transcription quantitative real-time polymerase chain reaction. CTC aneuploidy and its number distribution was detected and the detection of various blood markers was performed. The diagnostic accuracy was determined through receiver operating characteristic curve (ROC) drawn among the groups. The total number of CTCs and aneuploidies in patients with early-stage lung adenocarcinoma was higher than in patients with benign pulmonary nodules and healthy people. Patients with early-stage lung adenocarcinoma had significantly higher levels of miR-223-3p and miR-486-5p than patients with benign pulmonary nodules and healthy people. ROC analysis found that the sensitivity and area under the ROC curve of CTCs combined with multiple blood markers for distinguishing patients with early-stage lung adenocarcinoma from those without lung nodules were 80.12% and 0.945%, respectively. The sensitivity and area under the ROC curve of the patients were 85.38% and 0.948%, respectively. The detection of CTCs, carcinoembryonic antigen, cytokeratin 19 fragment, miR-223-3p, and miR-486-5p was effective for early-stage lung adenocarcinoma and benign lung nodules. The diagnosis of miR-223-3p is clinically significant, as the accurate diagnostic index of miR-223-3p is better than that of CTCs and other blood indicators. However, CTCs combined with blood markers have the highest efficiency in diagnosing early-stage lung adenocarcinoma.

An Explainable Classification Method Based on Complex Scaling in Histopathology Images for Lung and Colon Cancer.

Lung and colon cancers are among the leading causes of human mortality and morbidity. Early diagnostic work up of these diseases include radiography, ultrasound, magnetic resonance imaging, and computed tomography. Certain blood tumor markers for carcinoma lung and colon also aid in the diagnosis. Despite the lab and diagnostic imaging, histopathology remains the gold standard, which provides cell-level images of tissue under examination. To read these images, a histopathologist spends a large amount of time. Furthermore, using conventional diagnostic methods involve high-end equipment as well. This leads to limited number of patients getting final diagnosis and early treatment. In addition, there are chances of inter-observer errors. In recent years, deep learning has shown promising results in the medical field. This has helped in early diagnosis and treatment according to severity of disease. With the help of EffcientNetV2 models that have been cross-validated and tested fivefold, we propose an automated method for detecting lung (lung adenocarcinoma, lung benign, and lung squamous cell carcinoma) and colon (colon adenocarcinoma and colon benign) cancer subtypes from LC25000 histopathology images. A state-of-the-art deep learning architecture based on the principles of compound scaling and progressive learning, EffcientNetV2 large, medium, and small models. An accuracy of 99.97%, AUC of 99.99%, F1-score of 99.97%, balanced accuracy of 99.97%, and Matthew's correlation coefficient of 99.96% were obtained on the test set using the EffcientNetV2-L model for the 5-class classification of lung and colon cancers, outperforming the existing methods. Using gradCAM, we created visual saliency maps to precisely locate the vital regions in the histopathology images from the test set where the models put more attention during cancer subtype predictions. This visual saliency maps may potentially assist pathologists to design better treatment strategies. Therefore, it is possible to use the proposed pipeline in clinical settings for fully automated lung and colon cancer detection from histopathology images with explainability.

The effect of nursing intervention combined with PD-1 inhibitor on platelets, white blood cells, tumor markers and quality of life in patients with lung cancer

ABSTRACT Tumor immunotherapy has become one of the important directions in the field of anti-tumor research. Among them, programmed death molecule-1 (PD-1) and its ligand (PD-L1) inhibitors have attracted considerable attention. This study analyzed the application effects of PD-1 inhibitors assisted nursing intervention in patients with lung cancer (LC). Sixty-eight patients with LC were divided into research group and control group randomly. Control group was treated with PD-1 inhibitor chemotherapy. Research group was treated with PD-1 inhibitors as auxiliary nursing intervention. Platelets, immune function indexes, tumor markers, and white blood cells were analyzed. Clinical efficacy was evaluated by traditional Chinese medicine (TCM) symptom score, survival quality of karnofsky performance scale (KPS) score, living quality of quality of life (QOL) score, and nausea and vomiting classification. Hemoglobin (HB), platelet (PLT) and serum white blood cells (WBC) levels in the two groups were decreased after treatment. HB, PLT and WBC levels were enhanced in research group versus control group. Moreover, carcino-embryonic antigen (CEA), carbohydrate antigen 199 (CA199) and CA125 levels in both groups were reduced after treatment. Compared with before treatment, the levels of cluster of differentiation (CD)3+, CD4+, CD4+/CD8+ in control group and the research group increased, while the CD8+ content was significantly decreased after treatment. And their content of the research group was significantly higher/lower than that of the control group. TCM symptom score, KPS score, QOL score and nausea and vomiting classification were improved in research group compared to control group. PD-1 inhibitors assisted nursing intervention can improve the living quality of patients with LC after chemotherapy.