Cancer Antigen Research Articles

Anti-tumoral Immunity and Chemo-preventive Effectiveness of Herbal Extracts of Curcumin, Ginger, Clove and Amygdaline in Ehrlich Ascites Carcinoma-Challenging Mice.

Due to its systemic toxicity, traditional chemotherapy of tumors is being taken into consideration. Herbal therapy, containing phytochemical polyphenol derivatives such as Curcumin (Cur), Ginger (Gin), Cloves (Clov) and Amygdaline (Amyg), is one of the numerous complementary and alternative approaches as an anti-cancer therapy and holds great promise for cancer chemo-prevention with fewer side effects. The current study was designated to assess anti-tumoral immunity and anti-cancer and chemo-preventive effectiveness of herbal extracts of Cur, Ginger, Clov and Amyg in Ehrlich Ascites Carcinoma (EAC)-challenging mice. Chemo-preventive efficacy of herbal extracts of Cur, Gin, Clov and Amyg were analyzed in vivo by examination of the apoptosis rate of EAC tumor cells by flow cytometry. The total numbers of EAC cells, splenocytes counts and leucocytes count with their differentials relative % in peripheral blood (PB) of EACchallenging mice were investigated. EAC-challenging mice treated with herbal extracts of Cur, Gin, Clov and Amyg showed a marked decline in EAC tumor cell count and a noticeable increase in apoptosis rate of EAC tumor cells, a remarkable decrease in serum level of cancer antigen 125 (CA-125) with an obvious increase in the number of splenocytes comparing to that in EAC-challenging mice treated with PBS alone. Moreover, the data indicated an insignificant change in the total leucocytes count and their differentials relative % of eosinophil, neutrophils, monocytes and lymphocytes in EAC-challenging mice treated with Cur and Amyg, but these parameters were markedly increased in EAC-challenging mice injected with Gin and Clov compared to that in EAC-challenging mice treated with PBS alone. To conclude, the herbal extracts of Cur, Gin, Clov and Amyg may have anti-tumoral immunity and anti-cancer potency and potential to reduce the resistance to cancer conventional chemotherapy and exert cancer chemo-protective approaches with low adverse effects. Further research is necessary to determine the regimen's toxicity on various tissues and organs and to connect the diagnostic and therapeutic approaches used in the regimen's biomedical use.

Evaluation of Serum Cancer Antigen (CA)-125 Levels as a Biomarker for Ovarian Lesions: Correlation With Histopathological Diagnosis and Clinical Outcomes.

Ovarian cancer is a significant cause of morbidity and mortality among women worldwide. Early detection and accurate diagnosis are crucial for improving patient outcomes. Serum biomarkers, such as cancer antigen 125 (CA-125), have shown promise in aiding the diagnosis and monitoring of ovarian lesions. This study aimed to assess the utility of serum CA-125 levels as a biomarker for ovarian lesions, correlating with histopathological diagnosis and clinical outcomes. A prospective observational study was conducted, enrolling 144 female patients presenting with suspected ovarian lesions at a hospital or clinic. Demographic data, physical examination findings, imaging results, and serum CA-125 levels were collected at baseline. Patients underwent laparoscopic or surgical intervention for tissue biopsy or resection, and a histopathological examination was performed to confirm the diagnosis. Clinical outcomes, including response to treatment and disease recurrence, were monitored during follow-up visits. The baseline characteristics of the study population showed significant differences between participants with and without ovarian lesions. Older age (mean age 54.8 vs. 45.6) years; p < 0.001) and higher serum CA-125 levels (65.9 vs. 28.6 U/mL, p < 0.001) were associated with ovarian pathology. Histopathological analysis revealed benign cystadenoma as the most prevalent subtype (31.8%), followed by serous carcinoma (27.3%) and borderline tumors (22.7%). Clinical outcomes indicated favorable treatment responses in most patients, with 77.3% achieving complete remission and 15.9% experiencing recurrence. However, elevated CA-125 levels were significantly associated with poorer treatment response (p < 0.001) and higher rates of recurrence, suggesting its potential as a prognostic biomarker for ovarian lesions. Serum CA-125 levels serve as a valuable biomarker for ovarian lesions, aiding in the diagnosis and monitoring of ovarian cancer. However, its utility is limited by its lack of specificity, particularly in differentiating between benign and malignant ovarian lesions. Integrating CA-125 with other clinical parameters and imaging modalities may enhance diagnostic accuracy and improve patient outcomes in ovarian cancer management.

Assessing the rates of false-positive ovarian cancer screenings and surgical interventions associated with screening tools: a systematic review

ObjectiveEarly detection of ovarian cancer can improve patient outcomes; however, screening tests can yield false-positive results, leading to unnecessary surgical interventions. This systematic review explores the prevalence of false-positive ovarian...

Antitumor, antioxidant, and anti-inflammatory activity of spirulina against 7,12-dimethylbenzanthracene-induced mammary cancer

Background Breast cancer is the most abundant malignancies worldwide; however, its current therapies encounter drug resistance or exhibit numerous side effects. Marine and freshwater algal biomasses, such as spirulina, are rich with many biological active components. Objective The main objective of the current study was to investigate the therapeutic, antioxidant, and immune-modulating efficiency of spirulina on breast tumor modelled female rats, especially through the inhibition of the phosphoinositide 3-kinases/Akt/mammalian target of rapamycin pathway. Materials and methods 7,12-dimethylbenzanthracene (DMBA)-induced mammary cancer rats were ingested with spirulina (500 mg/kg/day) for 6 weeks, then blood and tissue samples of normal and spirulina-treated cancer rats were obtained and tested for biochemical, immunological, and histopathological assessments. Cancer model is used in this experiment. Results The results showed that spirulina is rich in phenolic compounds that have high scavenger activity and reducing power reflecting the antioxidant potential of spirulina. Treatment of DMBA-induced mammary cancer rats with spirulina resulted in improvement in mammary oxidative stress status that was distorted due to DMBA administration; meanwhile, superoxide dismutase, glutathione peroxidase, and reduced glutathione values were elevated significantly coupled with a marked drop in nitric oxide and malondialdehyde levels. In addition, spirulina boosts the immune-modulating response against tumor as the serum proinflammatory cytokines (tumor necrosis factor alpha, interlukin-1 beta, and interlukin-6) were markedly downregulated, and associated with inhibition of Akt and mammalian target of rapamycin pathway; this in turn suppress the tumor proliferation and progression. Furthermore, the prognosis of the treatment was indicated by the clear reduction of serum cancer antigen 15.3 level accompanied by elevation in serum level of the apoptotic biomarkers (caspase-3 and CD4) inferring the upregulation of tumor suppressor genes. Similarly, spirulina ameliorated lipid profile and the biochemical markers of hepatorenal functions (alanine transaminase, aspartate transaminase, urea, and creatinine) that were disturbed by DMBA; therefore, it has a positive impact on the body health. These biochemical improvements were associated with a notable improvement in the histological architecture of the mammary tissue. Conclusion In conclusion, spirulina has proved considerable antitumor, antioxidant, and anti-inflammatory activities against DMBA-induced mammary cancer.

Aptamer-enabled electrochemical bioplatform utilizing surface-modified g-C3N4/MoS2/PANI nanocomposite for detection of CA125 biomarker

Detecting ovarian cancer at an early stage is crucial for enhancing patient outcomes, underscoring the demand for an efficient and non-invasive detection method. Cancer antigen 125 (CA125) is a vital biomarker in ovarian cancer detection, and there is a pressing demand to develop a quick, sensitive, and simple detection method. Nanobiosensors are increasingly being used by scientists due to their high selectivity and sensitivity, allowing for the swift and precise detection of a wide range of biomarkers. This study aimed to design and fabricate an electrochemical nanobiosensor that could accurately and selectively detect CA125. The nanobiosensor employed graphitic carbon nitrides, molybdenum disulfide, and polyaniline (g-C3N4/MoS2/PANI) to stabilize aptamer strands on a modified glassy carbon electrode. The aptasensor was used to perform electrochemical detection of labeled CA125, utilizing methylene blue and label-free ferrocyanide methods. Ferrocyanide and methylene blue detection limits were determined to be 0.196 U.mL−1 for ferrocyanide and 0.196 U.mL−1 for methylene blue, with a linear detection range of 2–10 U.mL−1 for linear detection. The study results showed that the modified electrode exhibited high selectivity towards CA125 and superior stability compared to other biomolecules. The electrochemical aptasensor also displayed impressive performance when analyzing the serum of patients and healthy people. These findings hold significant promise for future investigation in ovarian cancer diagnosis. This novel electrochemical nanobiosensor may aid in the early detection and management of ovarian cancer, ultimately leading to better patient outcomes.

Elevated Serum Tumor Markers (HE4 and ROMA Score) and Increased Treg Cells Distinguished Ovarian Cancer and Benign Tumor

BACKGROUND: Tumor markers such as human epididymis protein 4 (HE4), cancer antigen 125 (CA-125), and risk of ovarian malignancy algorithm (ROMA) are frequently utilized for diagnostic and prognostic purposes. Lymphocytes, essential immune cells, play a significant role in eliminating cancer cells. However, the precise correlation between tumor markers and lymphocytes remains incompletely elucidated. The aim of this study was to explore the correlation between tumor markers and lymphocyte subtype profiles in differentiating ovarian cancer and benign tumors.METHODS: This was a cross-sectional study involving 12 ovarian cancer and 17 benign ovarian tumor patients. Blood samples were collected for the characterization of T lymphocytes, B lymphocytes, natural killer (NK), and T regulatory (Treg), which were analyzed using flowcytometry. Additionally, tumor markers HE4 and CA-125 were measured from patient serum using the chemiluminescent microparticle immunoassay (CMIA) method.RESULTS: Benign ovarian tumors and ovarian cancer can be distinguished by a significant increase in HE4 levels (p=0.004), ROMA (p=0.004), and Treg cells (CD4+/CD25+/FOXP3+, p=0.017). Furthermore, the correlation between tumor markers and lymphocytes indicates that an increase in ROMA was weakly correlated with an increase in the percentage of T regulatory cells (CD4+/CD25+/FOXP3+, r=0.553, p=0.006) and B lymphocytes (CD19+, r=0.528, p=0.010), accompanied by a decrease in the number of T lymphocytes (CD3+, r=-0.598, p=0.003), T helper lymphocytes (CD3+CD4+, r=-0.594, p=0.003), and cytotoxic lymphocytes (CD3+CD8+, r=-0.510, p=0.013).CONCLUSION: The elevation of serum tumor markers (HE4 and ROMA) accompanied by an increase in Treg cells can distinguish between benign ovarian tumor patients and ovarian cancer patients.KEYWORDS: tumor marker, CA-125, HE4, ROMA, subtype of lymphocytes, ovarian cancer

Evaluation of Serum Cytokeratines, Thymidine Kinase, and Growth Factors as Cancer Biomarkers in Colorectal Cancer.

Classical serum cancer biomarkers, such as carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA 19-9), remain important tools in colorectal cancer (CRC) management for disease follow up. However, their sensitivity and specificity are low for diagnostic and prognostic evaluation. The aim of this study was to evaluate the potential of biomarkers reflecting biological activity of tumors - tissue polypeptide specific antigen (TPS), cytokeratin fragment 19 (CYFRA 21-1), thymidine kinase (TK), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGF-BP3) - together with the CEA and CA 19-9 in CRC diagnosis and prognosis. This is a retrospective study including 148 CRC patients and 68 age-matched healthy subjects. Serum biomarkers were measured in pre-operative serum samples using immunoanalytical methods. The end-point for the diagnostic evaluation was the area under the receiving operating characteristic curve (AUC ROC) of the biomarkers. The end-point for the prognostic evaluation was overall survival. Serum levels of CEA, CA 19-9, TPS, and TK were significantly increased in CRC early-stage patients compared with healthy controls. Each of the studied biomarkers had AUC between 0.6 and 0.7. Analysis of survival demonstrated that the patients with CEA, CA 19-9, cytokeratin, and TK above optimal cut offs had significantly shorter survival. A multivariate analysis performed on all the study biomarkers resulted in the selection of CYFRA 21-1 as the best performing biomarker with hazard ratio 10.413. The combination of cytokeratins and thymidine kinase with classical cancer biomarkers enables the prediction of tumor aggressiveness and long-term prognosis.

Machine Learning-Enhanced Extraction of Biomarkers for High-Grade Serous Ovarian Cancer from Proteomics Data

Comprehensive biomedical proteomic datasets are accumulating exponentially, warranting robust analytics to deconvolute them for identifying novel biological insights. Here, we report a strategic machine learning (ML)-based feature extraction workflow that was applied to unveil high-performing protein markers for high-grade serous ovarian carcinoma (HGSOC) from publicly available ovarian cancer tissue and serum proteomics datasets. Diagnosis of HGSOC, an aggressive form of ovarian cancer, currently relies on diagnostic methods based on tissue biopsy and/or non-specific biomarkers such as the cancer antigen 125 (CA125) and human epididymis protein 4 (HE4). Our newly developed ML-based approach enabled the identification of new serum proteomic biomarkers for HGSOC. The performance verification of these marker combinations using two independent cohorts affirmed their outperformance against known biomarkers for ovarian cancer including clinically used serum markers with >97% AUC. Our analysis also added novel biological insights such as enriched cancer-related processes associated with HGSOC.

Elucidating the role of liver enzymes as markers and regulators in ovarian cancer: a synergistic approach using Mendelian randomization, single-cell analysis, and clinical evidence

ObjectiveTo investigate the association between liver enzymes and ovarian cancer (OC), and to validate their potential as biomarkers and their mechanisms in OC. MethodsGenome-wide association studies for OC and levels of enzymes such as Alkaline phosphatase (ALP), Aspartate aminotransferase (AST), Alanine aminotransferase, and gamma-glutamyltransferase were analyzed. Univariate and multivariate Mendelian randomization (MR), complemented by the Steiger test, identified enzymes with a potential causal relationship to OC. Single-cell transcriptomics from the GSE130000 dataset pinpointed pivotal cellular clusters, enabling further examination of enzyme-encoding gene expression. Transcription factors (TFs) governing these genes were predicted to construct TF-mRNA networks. Additionally, liver enzyme levels were retrospectively analyzed in healthy individuals and OC patients, alongside the evaluation of correlations with cancer antigen 125 (CA125) and Human Epididymis Protein 4 (HE4).ResultsA total of 283 single nucleotide polymorphisms (SNPs) and 209 SNPs related to ALP and AST, respectively. Using the inverse-variance weighted method, univariate MR (UVMR) analysis revealed that ALP (P = 0.050, OR = 0.938) and AST (P = 0.017, OR = 0.906) were inversely associated with OC risk, suggesting their roles as protective factors. Multivariate MR (MVMR) confirmed the causal effect of ALP (P = 0.005, OR = 0.938) on OC without reverse causality. Key cellular clusters including T cells, ovarian cells, endothelial cells, macrophages, cancer-associated fibroblasts (CAFs), and epithelial cells were identified, with epithelial cells showing high expression of genes encoding AST and ALP. Notably, TFs such as TCE4 were implicated in the regulation of GOT2 and ALPL genes. OC patient samples exhibited decreased ALP levels in both blood and tumor tissues, with a negative correlation between ALP and CA125 levels observed.ConclusionThis study has established a causal link between AST and ALP with OC, identifying them as protective factors. The increased expression of the genes encoding these enzymes in epithelial cells provides a theoretical basis for developing novel disease markers and targeted therapies for OC.

Combination of sarcopenia and systemic inflammation-based markers for predicting the prognosis of patients undergoing pancreaticoduodenectomy for pancreatic cancer.

This study aimed to evaluate the effects of sarcopenia and inflammation on the prognosis of patients with pancreatic cancer after pancreaticoduodenectomy. Eighty patients who had undergone pancreaticoduodenectomy for pancreatic cancer between July 2010 and December 2023 were included in this study. The psoas muscle index was used to assess sarcopenia. The C-reactive protein-to-albumin ratio, prognostic nutritional index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio were used to calculate the preoperative inflammatory marker levels. The prognostic factors for overall survival were determined using Cox regression analysis. Twenty-four patients were diagnosed with sarcopenia. Sarcopenia showed a significant association with advanced tumor stage. Univariate analysis revealed a significant reduction in overall survival in patients with a prognostic nutritional index of <45, C-reactive protein-to-albumin ratio of ≥0.047, cancer antigen 19-9 levels of ≥130 U/mL, sarcopenia, lymph node metastasis, and vascular invasion. Multivariate analysis revealed that a C-reactive protein-to-albumin ratio of ≥0.047 (hazards ratio, 3.383; 95% confidence interval: 1.384-8.689; p< 0.001), cancer antigen 19-9 levels of ≥130 U/mL (hazards ratio, 2.720; 95% confidence interval: 1.291-6.060; p = 0.008), sarcopenia (hazards ratio, 3.256; 95% confidence interval: 1.535-7.072; p = 0.002) and vascular invasion (hazards ratio, 2.092; 95% confidence interval: 1.057-4.170; p = 0.034) were independent predictors of overall survival. Overall survival in the sarcopenia and high C-reactive protein-to-albumin ratio groups was significantly poorer than that in the non-sarcopenia and low C-reactive protein-to-albumin ratio and sarcopenia or high C-reactive protein-to-albumin ratio groups. Sarcopenia and a high C-reactive protein-to-albumin ratio are independent prognostic factors in patients with pancreatic cancer after pancreaticoduodenectomy. Thus, sarcopenia may have a better prognostic value when combined with the C-reactive protein-to-albumin ratio.

Enhancing the diagnostic accuracy of colorectal cancer through the integration of serum tumor markers and hematological indicators with machine learning algorithms.

Colorectal cancer has a high incidence and mortality rate due to a low rate of early diagnosis. Therefore, efficient diagnostic methods are urgently needed. This study assesses the diagnostic effectiveness of Carbohydrate Antigen 19-9 (CA19-9), Carcinoembryonic Antigen (CEA), Alpha-fetoprotein (AFP), and Cancer Antigen 125 (CA125) serum tumor markers for colorectal cancer (CRC) and investigates a machine learning-based diagnostic model incorporating these markers with blood biochemical indices for improved CRC detection. Between January 2019 and December 2021, data from 800 CRC patients and 697 controls were collected; 52 patients and 63 controls attending the same hospital in 2022 were collected as an external validation set. Markers' effectiveness was analyzed individually and collectively, using metrics like ROC curve AUC and F1 score. Variables chosen through backward regression, including demographics and blood tests, were tested on six machine learning models using these metrics. In the case group, the levels of CEA, CA199, and CA125 were found to be higher than those in the control group. Combining these with a fourth serum marker significantly improved predictive efficacy over using any single marker alone, achieving an Area Under the Curve (AUC) value of 0.801. Using stepwise regression (backward), 17 variables were meticulously selected for evaluation in six machine learning models. Among these models, the Gradient Boosting Machine (GBM) emerged as the top performer in the training set, test set, and external validation set, boasting an AUC value of over 0.9, indicating its superior predictive power. Machine learning models integrating tumor markers and blood indices offer superior CRC diagnostic accuracy, potentially enhancing clinical practice.

Recurrent disease detection after resection of pancreatic ductal adenocarcinoma using a recurrence-focused surveillance strategy (RADAR-PANC): protocol of an international randomized controlled trial according to the Trials within Cohorts design

BackgroundDisease recurrence remains one of the biggest concerns in patients after resection of pancreatic ductal adenocarcinoma (PDAC). Despite (neo)adjuvant systemic therapy, most patients experience local and/or distant PDAC recurrence within 2 years. High-level evidence regarding the benefits of recurrence-focused surveillance after PDAC resection is missing, and the impact of early detection and treatment of recurrence on survival and quality of life is unknown. In most European countries, recurrence-focused follow-up after surgery for PDAC is currently lacking. Consequently, guidelines regarding postoperative surveillance are based on expert opinion and other low-level evidence. The recent emergence of more potent local and systemic treatment options for PDAC recurrence has increased interest in early diagnosis. To determine whether early detection and treatment of recurrence can lead to improved survival and quality of life, we designed an international randomized trial.MethodsThis randomized controlled trial is nested within an existing prospective cohort in pancreatic cancer centers in the Netherlands (Dutch Pancreatic Cancer Project; PACAP) and the United Kingdom (UK) (Pancreas Cancer: Observations of Practice and survival; PACOPS) according to the “Trials within Cohorts” (TwiCs) design. All PACAP/PACOPS participants with a macroscopically radical resection (R0-R1) of histologically confirmed PDAC, who provided informed consent for TwiCs and participation in quality of life questionnaires, are included. Participants randomized to the intervention arm are offered recurrence-focused surveillance, existing of clinical evaluation, serum cancer antigen (CA) 19–9 testing, and contrast-enhanced computed tomography (CT) of chest and abdomen every three months during the first 2 years after surgery. Participants in the control arm of the study will undergo non-standardized clinical follow-up, generally consisting of clinical follow-up with imaging and serum tumor marker testing only in case of onset of symptoms, according to local practice in the participating hospital. The primary endpoint is overall survival. Secondary endpoints include quality of life, patterns of recurrence, compliance to and costs of recurrence-focused follow-up, and the impact on recurrence-focused treatment.DiscussionThe RADAR-PANC trial will be the first randomized controlled trial to generate high level evidence for the current clinical equipoise regarding the value of recurrence-focused postoperative surveillance with serial tumor marker testing and routine imaging in patients after PDAC resection. The Trials within Cohort design allows us to study the acceptability of recurrence-focused surveillance among cohort participants and increases the generalizability of findings to the general population. While it is strongly encouraged to offer all trial participants treatment at time of recurrence diagnosis, type and timing of treatment will be determined through shared decision-making. This might reduce the potential survival benefits of recurrence-focused surveillance, although insights into the impact on patients’ quality of life will be obtained.Trial registrationClinicaltrials.gov, NCT04875325. Registered on May 6, 2021.

Prospects for Using 3D Modeling and Biomarkers in Differential Diagnosis of Endometrioid Ovarian Cysts

Background. Ovarian heterotopias are quite successfully diagnosed with ultrasound examinations. Considering the high risk of spread of the disease, as well as reproductive consequences (infertility, pelvic adhesive processes, chronic pelvic pain syndrome, dysmenorrhea), early differential diagnosis of endometrioid cysts and, accordingly, early initiation of treatment are of particular importance.Objective: to combine ultrasound criteria using 3D visualization and the content of biomarkers to verify stage 1–2 endometrioid ovarian cysts.Material and methods. In 59 infertile women with endometrioid ovarian cysts, in the dynamics of the menstrual cycle, ultrasound examinations were performed using Acuson S2000 (Siemens, Germany) and Voluson E8 (General Electric, USA) with the possibility of Doppler measurements and three-dimensional reconstruction of tissue images. Also, in laboratories “Invitro”, “Hemotest”, “Nauka” (Samara, Russia) the biomarkers were determined: interleukins IL-1β, IL-6, cancer antigen 125 (CA-125), human epididymis protein 4 (HE4) and the index by Risk of Ovarian Malignancy Algorithm (ROMA). The control group included 195 fertile women of reproductive age. In patients with endometrioid cysts, the diagnosis was subsequently confirmed morphologically.Results. Small unilateral and bilateral ovarian cysts corresponding to stage 1–2 endometriosis by revised American Fertility Society classification (rAFS) were clearly differentiated in 56 (94.9%) patients, in 3 (5.4%) of them the ultrasound result was questionable. In 48 (81.4%) women the lesion was unilateral and in 11 (18.6%) it was bilateral. The structure of cystic formations in all cases was hypoechoic, heterogeneous, in 36 (61.0%) cases it was finely cellular, without blood flow.Conclusion. Ovarian endometriomas in “gray scale” are round formations of reduced echogenicity and fine suspension, with an even, clear contour, not fused with the surrounding tissues, avascular, changing size depending on menstrual cycle phase. An ovarian mass may have a capsule with locus signals on Doppler. The sensitivity of ultrasound examination in “gray scale” in the presence of an endometrioid cyst is 94.6%.

Clinical relevance of circulating tumor DNA in ovarian cancer: current issues and future opportunities.

Ovarian cancer (OC) is the most lethal gynecologic malignancy worldwide. Due to the lack of effective screening and early detection strategies, many patients with OC are diagnosed with advanced disease, where treatment is rarely curative. Moreover, OC is characterized by high intratumor heterogeneity, which represents a major barrier to the development of effective treatments. Conventional tumor biopsy and blood-based biomarkers, such as cancer antigen 125 (CA125), have different limitations. Liquid biopsy has recently emerged as an attractive and promising area of investigation in oncology, due to its minimally invasive, safe, comprehensive, and real-time dynamic nature. Preliminary evidence suggests a potential role of liquid biopsy to refine OC management, by improving screening, early diagnosis, assessment of response to treatment, detection, and profiling of drug resistance. The current knowledge and the potential clinical value of liquid biopsy in OC is discussed in this review to provide an overview of the clinical settings in which its use might support and improve diagnosis and treatment.

Identification of novel therapeutic targets for chronic kidney disease and kidney function by integrating multi-omics proteome with transcriptome

BackgroundChronic kidney disease (CKD) is a progressive disease for which there is no effective cure. We aimed to identify potential drug targets for CKD and kidney function by integrating plasma proteome and transcriptome.MethodsWe designed a comprehensive analysis pipeline involving two-sample Mendelian randomization (MR) (for proteins), summary-based MR (SMR) (for mRNA), and colocalization (for coding genes) to identify potential multi-omics biomarkers for CKD and combined the protein–protein interaction, Gene Ontology (GO), and single-cell annotation to explore the potential biological roles. The outcomes included CKD, extensive kidney function phenotypes, and different CKD clinical types (IgA nephropathy, chronic glomerulonephritis, chronic tubulointerstitial nephritis, membranous nephropathy, nephrotic syndrome, and diabetic nephropathy).ResultsLeveraging pQTLs of 3032 proteins from 3 large-scale GWASs and corresponding blood- and tissue-specific eQTLs, we identified 32 proteins associated with CKD, which were validated across diverse CKD datasets, kidney function indicators, and clinical types. Notably, 12 proteins with prior MR support, including fibroblast growth factor 5 (FGF5), isopentenyl-diphosphate delta-isomerase 2 (IDI2), inhibin beta C chain (INHBC), butyrophilin subfamily 3 member A2 (BTN3A2), BTN3A3, uromodulin (UMOD), complement component 4A (C4a), C4b, centrosomal protein of 170 kDa (CEP170), serologically defined colon cancer antigen 8 (SDCCAG8), MHC class I polypeptide-related sequence B (MICB), and liver-expressed antimicrobial peptide 2 (LEAP2), were confirmed. To our knowledge, 20 novel causal proteins have not been previously reported. Five novel proteins, namely, GCKR (OR 1.17, 95% CI 1.10–1.24), IGFBP-5 (OR 0.43, 95% CI 0.29–0.62), sRAGE (OR 1.14, 95% CI 1.07–1.22), GNPTG (OR 0.90, 95% CI 0.86–0.95), and YOD1 (OR 1.39, 95% CI 1.18–1.64,) passed the MR, SMR, and colocalization analysis. The other 15 proteins were also candidate targets (GATM, AIF1L, DQA2, PFKFB2, NFATC1, activin AC, Apo A-IV, MFAP4, DJC10, C2CD2L, TCEA2, HLA-E, PLD3, AIF1, and GMPR1). These proteins interact with each other, and their coding genes were mainly enrichment in immunity-related pathways or presented specificity across tissues, kidney-related tissue cells, and kidney single cells.ConclusionsOur integrated analysis of plasma proteome and transcriptome data identifies 32 potential therapeutic targets for CKD, kidney function, and specific CKD clinical types, offering potential targets for the development of novel immunotherapies, combination therapies, or targeted interventions.

Circ_0004592: An auxiliary diagnostic biomarker for gastric cancer.

Gastric cancer (GC) has a high mortality rate, and robust diagnostic biomarkers are currently lacking. However, the clinical relevance of circular RNAs (circRNAs) as GC biomarkers remains largely unexplored. To evaluate the potential of novel circRNA circ_0004592 in the early screening and prognosis of GC. High-throughput sequencing of circRNAs was performed to screen for potential target molecules. Circ_0004592 expression was examined in GC tissues, cells, and plasma. Plasma samples were collected from healthy subjects' patients, as well as from patients with benign lesions, precancerous lesions, and GC, whereafter the diagnostic accuracy of circ_0004592 was evaluated. The correlation between circ_0004592 levels in plasma and clinicopathological data of patients with GC was further analyzed. Circ_0004592 was upregulated in both the tissue and plasma of patients with GC. Further, circ_0004592 expression was higher in patients with precancerous lesions than in healthy controls while being highest in patients with GC. In the same patient, the postoperative plasma level of circ_0004592 was lower than that in the preoperative period. Moreover, circ_0004592 level was significantly correlated with tumor differentiation, tumor depth, and lymph node metastasis. The area under the curve (AUC) of plasma circ_0004592 exhibited high sensitivity and specificity for differentiating patients with GC from healthy donors. Diagnosis based on circ_0004592, carcinoembryonic antigen, and cancer antigen 199 achieved a superior AUC and was highly sensitive. Plasma circ_0004592 may represent a potential non-invasive auxiliary diagnostic biomarker for patients with GC.

An ultrasensitive sandwich-type electrochemical immunosensor based on rGO-TEPA/ZIF67@ZIF8/Au and AuPdRu for the detection of tumor markers CA72-4

Cancer antigen 72–4 (CA72-4) is an important marker of cancer detection, and accurate detection of CA72-4 is urgently required. Herein, a sandwich-type immunosensor was constructed for detection CA72-4 based on composite nanomaterial as the substrate material and trimetal nanoparticles as the nanoprobe. The composite nanomaterial rGO-TEPA/ZIF67@ZIF8/Au used as a selective bio-recognition element were modified on the glassy carbon electrode (GCE) surface. Meanwhile, the electrochemical nanoprobes were fabricated through the AuPdRu trimeric metal. After the target antigen 72–4 were captured, the nanoprobes were further assembled to form an antibody1 (Ab1)- antigen-antibody2 (Ab2) nanoprobes sandwich-like system on the electrode surface. Then, hybrid the substrate material rGO-TEPA/ZIF67@ZIF8/Au and the AuPdRu trimeric metal nanoprobes efficiently catalyzed the reduction of H2O2 and amplified the electrochemical signals. Cyclic voltammetry (CV), differential pulse voltammetry (DPV), electrochemical impedance spectroscopy (EIS), and Chronoamperometry (I-T) methods were used to characterize the performance and detection capabilities for CA72-4 of the prepared immunosensors. The results showed that the detection limit was 1.8 × 10−5 U/mL (S/N = 3), and the linear range was 0.001–1000 U/mL. This study provides a new signal amplification strategy for electrochemical sensors and a theoretical basis for the clinical application of immunosensor to detect other tumor markers.

Auto-reduction of Au(III) on Fe-Doped, Pyrrolic-N-Modified nanoporous carbon derived from ZIF-8 for the electrochemical immunosensing of CA-125

Ovarian cancer (OC) is associated with high late mortality owing to hidden symptoms in the early stages and limited screening measurements. Therefore, it is urgent to develop a highly efficient label-free immunosensor for targeting cancer antigens. In this study, we developed a gold-loaded iron-doped nanoporous carbon (denoted as Au@Fe-NC) as an ideal substrate for cancer antigen detection with high specificity and sensitivity. First, an Fe, N-doped nanoporous carbon (Fe-NC) material was synthesized by carbonizing a Fe-doped metal-organic framework at 900 °C under continuous nitrogen flow. The resultant Fe-NC contains pyrrolic-N, which facilitates the auto-reduction of Au3+ to Au⁰ without requiring an external reducing agent. Thus, the Au@Fe-NC was spontaneously formed by mixing an aqueous HAuCl₄ solution with Fe-NC. The immunosensor developed using Au@Fe-NC exhibits outstanding stability as well as high sensitivity to carbohydrate antigen 125 (CA-125), a tumor marker, presenting a linear dynamic range of 0.1 pg mL−1 to 1 µg mL−1 and a detection limit of 0.1 pg mL−1. The proposed Au@Fe-NC-based immunosensor has the ability to detect CA-125 in human serum samples and is a promising material for OC diagnosis.

Ipilimumab and nivolumab plus UV1, an anticancer vaccination against telomerase, in advanced melanoma.

LBA9519 Background: The combination of ipilimumab (IPI) and nivolumab (NIVO) remains a standard of care for patients with advanced melanoma, especially those with poor prognostic factors, albeit with a significant risk of toxicity. Therapeutic cancer vaccines are ideally positioned to improve outcomes without significantly increasing toxicity. UV1 is a therapeutic cancer vaccine generating T-cell responses against the universal cancer antigen telomerase. In a Phase I trial in melanoma (N = 30), UV1 plus pembrolizumab demonstrated a tolerable safety profile, a complete response rate of 33%, median PFS of 18.9 months, and 2-year OS rate of 73.3%. Recently, results from a randomized Phase II trial indicated a longer overall survival and a higher response rate for previously treated patients with advanced mesothelioma receiving UV1 in combination with IPI-NIVO (1). Methods: In this Phase II, open-label, multicenter study, we randomly assigned treatment-naïve patients with unresectable or metastatic melanoma (stage IIIb-IIId or IV) to IPI 3mg/kg + NIVO 1mg/kg for 4 cycles, followed by NIVO 480 mg as maintenance, with or without 8 intradermal injections of 300 µg UV1 (+GM-CSF). The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review (BICR) according to RECIST 1.1. Secondary endpoints included overall survival (OS), objective response rate (ORR), duration of response, and safety. Results: A total of 156 patients underwent randomization; 78 patients were assigned to the IPI-NIVO-UV1 arm and 78 patients to the IPI-NIVO arm. The median age was 60, 48% had M1C or D disease, 38% had LDH &gt;upper limit of normal, and 42% had a positive BRAF mutation status. With a minimum follow-up of 18 months, the 12-month PFS rate was 57% in both arms (HR 0.95, 95% CI 0.59-1.55, p value 0.845). The ORR was similar with IPI-NIVO-UV1 compared to IPI-NIVO, at 60% vs 59%, respectively (Odds ratio 1.12, 95% CI 0.58-2.16, p value 0.867). The 12-month OS rate was 87% and 88%, respectively (HR 1.15, 95% CI 0.60-2.20, p value 0.674). The occurrence of grade &gt;3 adverse events was similar in both treatment arms. Conclusion: UV1 did not improve on outcomes of IPI-NIVO, in terms of PFS. Longer follow-up is required for the accurate assessment of OS. No significant toxicity increases were observed with the addition of UV1. Data from a biomarker driven cohort are awaited. 1. Helland et al, Eur J Cancer 2024. Clinical trial information: NCT04382664 .

A novel aptasensor platform for the detection of carcinoembryonic antigen using quartz crystal microbalance

In this study, a quartz crystal microbalance (QCM) aptasensor for carcinoembryonic antigen (CEA), a well-known biomarker for various cancer types, was reported, utilizing two different aptamers. To achieve this, a nanofilm of 4-mercaptophenyl was electrochemically attached to gold-coated QCM crystal surfaces via the reduction of 4-mercaptobenzenediazonium salt (4 MB-DAT) using cyclic voltammetry. Subsequently, gold nanoparticles (AuNP) were affixed to this structure, and then aptamers (antiCEA1 and antiCEA2) modified with SH-functional ends bound to AuNPs completed the modification. The analytical performance of the CEA sensor was evaluated through simultaneous QCM measurements employing CEA solutions ranging from 0.1 ng/mL to 25 ng/mL. The detection limit (LOD) for CEA was determined to be 102 pg/mL for antiCEA1 and 108 pg/mL for antiCEA2 aptamers. Interday and intraday precision and accuracy tests yielded maximum results of 4.3 and + 3.8, respectively, for both aptasensors, as measured by relative standard deviation (RSD%) and relative error (RE%). The kinetic data of the aptasensors resulted in affinity values (KD) of 0.43 ± 0.14 nM for antiCEA1 and 0.75 ± 0.42 nM for antiCEA2. These values were lower than the reported values of 3.9 nM and 37.8 nM for both aptamers, respectively. The selectivity of the aptasensor was evaluated by measuring the signal changes caused by alpha-fetoprotein (AFP), cancer antigen (CA-125), and vascular endothelial growth factor (VEGF-165) individually and together at a concentration of 500 ng/mL, resulting in a maximum 4.1 % change, which was comparable to precision and accuracy values reported in the literature. After confirming the selectivity of the aptamers, recovery experiments were conducted using spiked commercial serum samples to simulate real samples, and the lowest recovery value obtained was 95.4 %. It was determined that two different aptasensors could be successfully used for the QCM-based detection of CEA in this study.