Chemical Proteomic Approach for In-Depth Glycosylation Profiling of Plasma Carcinoembryonic Antigen in Cancer Patients.

Carcinoembryonic antigen (CEA) of human plasma is a biomarker of many cancer diseases, and its N-glycosylation accounts for 60% of molecular mass. It is highly desirable to characterize its glycoforms for providing additional dimension of features to increase its performance in prognosis and diagnosis of cancers. However, to systematically characterize its site-specific glycosylation is challenging because of its low abundance. Here, we developed a highly sensitive strategy for in-depth glycosylation profiling of plasma CEA through chemical proteomics combined with multienzymatic digestion. A trifunctional probe was utilized to generate covalent bond of plasma CEA and its antibody upon UV irradiation. As low as 1 ng/ml CEA in plasma could be captured and digested with trypsin and chymotrypsin for intact glycopeptide characterization. Twenty six of 28 potential N-glycosylation sites were well identified, which were the most comprehensive N-glycosylation site characterization of CEA on intact glycopeptide level as far as we known. Importantly, this strategy was applied to the glycosylation analysis of plasma CEA in cancer patients. Differential site-specific glycoforms of plasma CEA were observed in patients with colorectal cancers (CRCs) and lung cancer. The distributions of site-specific glycoforms were different as the progression of CRC, and most site-specific glycoforms were overexpressed in stage II of CRC. Overall, we established a highly sensitive chemical proteomic method to profile site-specific glycosylation of plasma CEA, which should generally applicable to other well-established cancer glycoprotein biomarkers for improving their cancer diagnosis and monitoring performance.

Inhibition of CEACAM1 expression in cytokine-activated neutrophils using JAK inhibitors.

OBJECTIVES: Carcinoembryonic-antigen-related cell-adhesion molecule 1 (CEACAM1) is an adhesion molecule that acts as a coinhibitory receptor in the immune system. We previously demonstrated that CEACAM1 is predominantly expressed on peripheral blood neutrophils in patients with RA. The aim of the present study was to investigate the effects of Janus kinase inhibitors (JAKi) on cytokine-activated human neutrophils and CEACAM1 expression. METHODS: Peripheral blood neutrophils were obtained from healthy subjects. Isolated neutrophils were stimulated with tumor necrosis factor-alpha (TNF-α) or granulocyte-macrophage colony-stimulating factor (GM-CSF) in the presence or absence of JAKi. The expression of CEACAM1 in peripheral blood neutrophils was analyzed by flow cytometry. Protein phosphorylation of signal transducer and activator of transcription (STAT)1, STAT3, and STAT5 was assessed by western blot using phospho-specific antibodies. RESULTS: We found that TNF-α-induced CEACAM1 expression was marginally suppressed after pretreatment with pan-JAK inhibitor, tofacitinib. Moreover, TNF-α induced STAT1 and STAT3 phosphorylation at the late stimulation phase (4 to 16 h). The expressions of CEACAM1 on neutrophils were markedly up-regulated by GM-CSF not by interleukin (IL)-6 stimulation. All JAKi inhibited GM-CSF-induced CEACAM1 expressions on neutrophils, however, the inhibitory effects of baricitinib were larger compared to those of tofacitinib or filgotinib. Moreover, CEACAM1 was marginally upregulated in interferon (IFN)-γ stimulated neutrophils. Similarly, JAKi inhibited IFN-γ-induced CEACAM1 expressions on neutrophils. CONCLUSIONS: We demonstrated that JAKi prevent GM-CSF-induced CEACAM1 expression in neutrophils, and JAKi-induced inhibition depends on their selectivity against JAK isoforms. These findings suggest that JAKi can modulate the expression of CEACAM1 in cytokine-activated neutrophils, thereby limiting their activation.

A novel risk classification model integrating CEA, ctDNA, and pTN stage for stage 3 colon cancer: a post hoc analysis of the IDEA-France trial.

BACKGROUND: We assessed the added value of incorporating carcinoembryonic antigen (CEA) to circulating tumor DNA (ctDNA) and pathological TN (pTN) stage for risk classification in stage 3 colon cancer (CC). PATIENTS AND METHODS: We retrospectively analyzed postoperative CEA values in patients with CC from the IDEA-France phase 3 trial. The relation between disease-free survival (DFS) and CEA was modeled through restricted cubic splines. Prognostic value of CEA, ctDNA, and pTN was assessed with the Kaplan-Meier method. Multivariate analysis was used to identify prognostic and predictive factors for DFS. RESULTS: Among 696 patients (35%), CEA values were retrievable, and for 405 (20%) both CEA and ctDNA were available. An optimized CEA threshold of 2 ng/mL was identified, the 3-year DFS was 66.4% for patients above the threshold and 80.9% for those below (HR, 1.74; 95% CI, 1.33-2.28, P < .001). In multivariate analysis, CEA ≥ 2 ng/mL contributed significantly to model variability, becoming an independent prognostic factor for DFS (HR, 1.82; 95% CI,1.27-2.59), alongside ctDNA (HR, 1.88; 95% CI, 1.16-3.03) and pTN (HR, 1.78; 95% CI, 1.24-2.54). A novel integrated risk classification combining CEA, ctDNA, and pTN stage reclassified 19.8% of pT4/N2 patients as low risk and 2.5% of pT3/N1 patients as high risk. This new classification demonstrated the 3-year DFS of 80.8% for low-risk patients and 55.4% for high-risk patients (HR, 2.66, 95% CI, 1.84-3.86, P < .001). CONCLUSIONS: Postoperative CEA value is a prognostic factor for DFS in stage 3 CC, independently of ctDNA and pTN. It advocates for systematic reporting in future adjuvant trials. Integrating both biomarkers with pTN could refine risk classification in stage 3 CC.

Normal CEA Levels After Neoadjuvant Chemotherapy and Cytoreduction with Hyperthermic Intraperitoneal Chemoperfusion Predict Improved Survival from Colorectal Peritoneal Metastases.

BACKGROUND: Normal carcinoembryonic antigen (CEA) levels (≤ 2.5 ng/ml) after resection of localized colorectal cancer or liver metastases are associated with improved survival, however, these trends are understudied for colorectal peritoneal metastases (CRPM). PATIENTS AND METHODS: We conducted a retrospective single-institution study of patients with CRPM undergoing cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS/HIPEC) with and without neoadjuvant chemotherapy (NACT). CEA was measured before and after NACT and within 3 months after CRS/HIPEC. RESULTS: A total of 253 patients (mean age 55.3 years) with CRPM undergoing CRS/HIPEC had complete CEA data and 191 also underwent NACT with complete data. The median peritoneal carcinomatosis index score (PCI) of the overall cohort was 12 and 82.7% of patients had complete cytoreduction (CC0). In total, 64 (33.5%) patients had normal CEA levels after NACT with a median overall survival (OS) of 45.2 months compared with those with an elevated CEA (26.4 months, p = 0.004). Patients with normal CEA after NACT had a lower PCI found at the time of surgery than those with elevated CEA (10 versus 14, p < 0.001), 68 (26.9%) patients with an elevated preoperative CEA level experienced normalization after CRS/HIPEC, and 118 (46.6%) patients had elevated CEA after CRS/HIPEC. Patients who experienced normalization demonstrated similar OS to patients that had normal CEA levels pre- and post-surgery and improved OS compared with those with elevated postop CEA (median 41.9 versus 47 months versus 17.1 months, respectively, p < 0.001). CONCLUSIONS: Normal CEA levels after NACT and/or CRS/HIPEC are associated with improved survival for patients with CRPM. Patients that normalize CEA levels after surgery have similar survival to those with normal preoperative levels.

Clinical Significance of the Post/Preoperative Anti-p53 Antibody Ratio in Predicting the Prognosis of Patients with Colorectal Cancer after Curative Surgery and Its Usefulness in Combination with Carcinoembryonic Antigen.

INTRODUCTION: Anti-p53 antibody (p53Ab) is useful for monitoring colorectal cancer (CRC) recurrence. We retrospectively analyzed the clinical impact of p53Ab ratio (p53R) before and after surgery to predict recurrence in patients with CRC. METHODS: In total, 1,223 patients with stage I-III CRC who underwent curative surgery between January 2005 and December 2019 were enrolled in this retrospective study. In patients with elevated p53Ab levels, p53R was calculated by measuring p53Ab levels within 1 month preoperatively and 3 months postoperatively. The optimal p53R level was determined, and its relationship with clinicopathological factors and prognosis was examined. We also evaluated the efficacy of the combination of p53R and preoperative carcinoembryonic antigen (CEA) values. RESULTS: Overall, 341 patients (27.9%) showed elevated p53Ab levels. Preoperative p53Ab levels were significantly associated with tumor location, lymphatic invasion, and venous invasion. The p53R level was significantly higher in patients with recurrent disease. Patients with high p53R levels had significantly shorter relapse-free survival than those with low p53R levels (p < 0.001). When p53R was combined with preoperative CEA values, specificity improved to 0.97, with an accuracy of 0.88. CONCLUSION: In patients with CRC and elevated preoperative p53Ab levels, p53R expression may be prognostically useful after radical resection. Furthermore, the combination of p53R and preoperative CEA levels may be useful for postoperative follow-ups.

Intraperitoneal administration of carcinoembryonic antigen-directed chimeric antigen receptor T cells is a robust delivery route for effective treatment of peritoneal carcinomatosis from colorectal cancer in pre-clinical study.

BACKGROUND AIMS: Peritoneal carcinomatosis (PC) from colorectal cancer (CRC) is a highly challenging disease to treat. Systemic chimeric antigen receptor (CAR) T cells have shown impressive efficacy in hematologic malignancies but have been less effective in solid tumors. We explored whether intraperitoneal (i.p.) administration of CAR T cells could provide an effective and robust route of treatment for PC from CRC. METHODS: We generated second-generation carcinoembryonic antigen (CEA)-specific CAR T cells. Various animal models of PC with i.p. and extraperitoneal metastasis were treated by i.p. or intravenous (i.v.) administration of CEA CAR T cells. RESULTS: Intraperitoneally administered CAR T cells exhibited superior anti-tumor activity compared with systemic i.v. cell infusion in an animal model of PC. In addition, i.p. administration conferred a durable effect and protection against tumor recurrence and exerted strong anti-tumor activity in an animal model of PC with metastasis in i.p. or extraperitoneal organs. Moreover, compared with systemic delivery, i.p. transfer of CAR T cells provided increased anti-tumor activity in extraperitoneal tumors without PC. This phenomenon was further confirmed in an animal model of pancreatic carcinoma after i.p. administration of our newly constructed prostate stem cell antigen-directed CAR T cells. CONCLUSIONS: Taken together, our data suggest that i.p. administration of CAR T cells may be a robust delivery route for effective treatment of cancer.

Conditional survival and the prognostic value of serum carcinoembryonic antigen level in oldest old with colorectal cancer.

BACKGROUND: To evaluate the clinical value of serum CEA levels and their implications on the diagnostic value of the conventional TNM staging system in the oldest-old patients with colorectal cancer (CRC). METHODS: The recruited subjects were colorectal cancer patients aged 85 and older. The cutoff value for normal CEA level is 5 ng/mL. Patients with elevated CEA levels were categorized as stage C1, and those with normal CEA levels as stage C0. A number of Cox proportional hazard regression models were established to evaluate the prognosis of different prognostic factors with hazard ratios (HRs) and 95% confidence intervals (CIs). The Kaplan-Meier method was utilized to display the disparate prognostic impact of multiple clinicopathological factors with the log-rank test. RESULTS: A total of 17,359 oldest-old patients diagnosed with CRC were recruited from the SEER database. The conditional survival of oldest-old patients with CRC was dismal with a 1-year conditional survival of only 11%, 18%, and 30% for patients surviving 1, 3, and 5 years, respectively. Patients with stage C1 exhibited a 48.5% increased risk of CRC-specific mortality compared with stage C0 (HR = 1.485, 95%CI = 1.393-1.583, using stage C0 patients as the reference, P < 0.001). All the stage C0 patients indicated lower HRs relative to the corresponding stage C1 patients. CONCLUSIONS: Dismal conditional survival of oldest-old patients with CRC should be given additional consideration. C stage influences the prognosis of oldest-old patients with CRC.

Fabrication of rGO-decorated hBNNS hybrid nanocomposite via organic-inorganic interfacial chemistry for enhanced electrocatalytic detection of carcinoembryonic antigen.

Organic-inorganic hybrid nanocomposites (OIHN), with tailored surface chemistry, offer ultra-sensitive architecture capable of detecting ultra-low concentrations of target analytes with precision. In the present work, a novel nano-biosensor was fabricated, acquainting dynamic synergy of reduced graphene oxide (rGO) decorated hexagonal boron nitride nanosheets (hBNNS) for detection of carcinoembryonic antigen (CEA). Extensive spectroscopic and microscopic analyses confirmed the successful hydrothermal synthesis of cross-linked rGO-hBNNS nanocomposite. Uniform micro-electrodes of rGO-hBNNS onto pre-hydrolyzed ITO were obtained via electrophoretic deposition (EPD) technique at low DC potential (15 V). Optimization of antibody incubation time, pH of supporting electrolyte, and immunoelectrode preparation was thoroughly investigated to enhance nano-biosensing efficacy. rGO-modified hBNNS demonstrated 29% boost in electrochemical performance over bare hBNNS, signifying remarkable electro-catalytic activity of nano-biosensor. The presence of multifunctional groups on the interface facilitated stable crosslinking chemistry, increased immobilization density, and enabled site-specific anchoring of Anti-CEA, resulting in improved binding affinity. The nano-biosensor demonstrated a remarkably low limit of detection of 5.47 pg/mL (R2 = 0.99963), indicating exceptional sensitivity and accuracy in detecting CEA concentrations from 0 to 50 ng/mL. The clinical evaluation confirmed its exceptional shelf life, minimal cross-reactivity, and robust recovery rates in human serum samples, thereby unraveling the potential for early, highly sensitive, and reliable CEA detection.

Predictive value of flexible proctosigmoidoscopy and laboratory findings for complete clinical responses after neoadjuvant chemoradiotherapy in patients with locally advanced primary rectal cancer: a retrospective cohort study.

PURPOSE: Colorectal cancer is the second leading cause of cancer death worldwide. Standard treatments for locally advanced rectal cancer include neoadjuvant chemoradiotherapy and total mesorectal excision (TME), which are associated with significant morbidity. After neoadjuvant therapy, one-third of patients achieve a pathological complete response (pCR) and are eligible for a watch-and-wait approach without TME. The purpose of this study was to determine the potential predictors of pCR before surgery. METHODS: The demographic, clinical, and endoscopic data of 119 patients with primary locally advanced rectal cancer without distant metastasis who underwent restaging endoscopy and TME 6-8 weeks after the end of neoadjuvant therapy were collected. The absence of tumor cells in the histological examination of the TME specimen after neoadjuvant therapy was considered pCR. Binary logistic regression and receiver operating characteristic curves were utilized for analysis. RESULTS: According to the multivariate logistic regression analysis, flattening of marginal tumor swelling (p value < 0.001, odds ratio = 100.605) emerged as an independent predictor of pCR in rectal cancer patients. Additionally, receiver operating characteristic curve analysis revealed that lower preoperative carcinoembryonic antigen and erythrocyte sedimentation rate levels predict pCR, with cutoffs of 2.15 ng/ml and 19.0 mm/h, respectively. CONCLUSION: Carcinoembryonic antigen and erythrocyte sedimentation rate, along with the presence of flattening of marginal tumor swelling, can predict pCR after neoadjuvant chemoradiotherapy in patients with primary rectal cancer. These factors offer a potential method for selecting candidates for conservative treatment based on endoscopic and laboratory findings.

Prognostic value of the postoperative carcinoembryonic antigen level in colorectal cancer: A meta-analysis.

BACKGROUND: Carcinoembryonic antigen (CEA) is one of the commonly used preoperative biomarkers for colorectal cancer (CRC), but no meta-analysis has evaluated the findings of all recently published studies to determine whether its postoperative level can serve as a prognostic indicator. METHODS: We conducted a systematic search for eligible literature from the PubMed, EMBASE, and Web of Science databases in October 2023. Studies that investigated the relationship between postoperative serum CEA levels and prognosis in CRC patients were included. Outcome indicators, including overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS)/recurrence-free survival (RFS), were analyzed using a fixed-effects or random-effects model. The pooled hazard ratios (HR) with 95% confidence intervals (CI) were used as effective values. RESULTS: This meta-analysis included 20 eligible studies involving 10,114 CRC patients from the East Asian and Western countries. A comprehensive analysis revealed that elevated postoperative CEA levels were associated with low OS (HR: 2.92, 95% CI: 2.36-3.62, and p < 0.000), DFS (HR: 2.81, 95% CI: 2.01-3.94, and p < 0.000), and RFS/PFS (HR: 2.52, 95% CI: 1.75-3.62, p < 0.000). A subgroup analysis by region, analysis type, distant metastasis, HR obtain method, sample size, postoperative measurement date, and study design demonstrated that the negative correlation observed between high serum CEA levels after surgery and poor prognosis was not significantly different between the subgroups. CONCLUSION: When CEA levels are found to be elevated during postoperative follow-up, more active intervention measures should be implemented to further improve the patient's survival outcomes.

Antiplatelet effects of the CEACAM1-derived peptide QDTT.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) restricts platelet activation via platelet collagen receptor GPVI/FcRγ-chain. In this study, screening against collagen-induced platelet aggregation was performed to identify functional CEACAM1 extracellular domain fragments. CEACAM1 fragments, including Ala-substituted peptides, were synthesized. Platelet assays were conducted on healthy donor samples for aggregation, cytotoxicity, adhesion, spreading, and secretion. Mice were used for tail bleeding and FeCl3-induced thrombosis experiments. Clot retraction was assessed using platelet-rich plasma. Extracellular segments of CEACAM1 and A1 domain-derived peptide QDTT were identified, while N, A2, and B domains showed no involvement. QDTT inhibited platelet aggregation. Ala substitution for essential amino acids (Asp139, Thr141, Tyr142, Trp144, and Trp145) in the QDTT sequence abrogated collagen-induced aggregation inhibition. QDTT also suppressed platelet secretion and "inside-out" GP IIb/IIIa activation by convulxin, along with inhibiting PI3K/Akt pathways. QDTT curtailed FeCl3-induced mesenteric thrombosis without significantly prolonging bleeding time, implying the potential of CEACAM1 A1 domain against platelet activation without raising bleeding risk, thus paving the way for novel antiplatelet drugs.

What is the context? The study focuses on Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and its role in platelet activation, particularly through the GPVI/FcRγ-chain pathway.The research aims to identify specific fragments of CEACAM1's extracellular domain that could restrict platelet activation, without increasing bleeding risk.What is new? The researchers identified a peptide called QDTT derived from the A1 domain of CEACAM1's extracellular segment. This peptide demonstrated the ability to inhibit platelet aggregation, secretion, and GP IIb/IIIa activation.The study also revealed that specific amino acids within the QDTT sequence were essential for its inhibitory effects on collagen-induced aggregation.What is the impact? The findings suggest that the A1 domain-derived peptide QDTT from CEACAM1 could serve as a potential basis for developing novel antiplatelet drugs. This peptide effectively limits platelet activation and aggregation without significantly prolonging bleeding time, indicating a promising approach to managing thrombosis and related disorders while minimizing bleeding risks.

The Value of Human Epididymal Protein 4, Carcinoembryonic Antigen and Alpha-Fetoprotein in the Early Diagnosis of Cervical Cancer.

OBJECTIVES: This research aimed to unveil the value of human epididymal protein 4 (HE4), carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) in the early diagnosis of cervical cancer. DESIGN: This was a clinical study. PARTICIPANTS: Sixty patients with cervical cancer stage IA-IIA (early stage cervical cancer group), 60 patients with cervical intraepithelial neoplasia (CIN) (disease control group), and 60 healthy women who had passed the physical examination (healthy control group) were selected. SETTING: The review was conducted in a Jiaxing First Hospital. METHODS: Sixty patients with cervical cancer stage IA-IIA (early stage cervical cancer group), 60 patients with CIN (disease control group), and 60 healthy women who had passed the physical examination (healthy control group) were selected. The expression levels of serum HE4, CEA, and AFP in the three groups were detected, and the correlation between the levels of serum HE4, CEA, and AFP and the clinicopathological characteristics of patients with early stage cervical cancer were analyzed, and the receiver operating characteristic (ROC) curves were plotted to identify the value of the single and triple tests of serum HE4, CEA, and AFP for the early stage diagnosis of cervical cancer. RESULTS: The levels of serum HE4, CEA, and AFP in the early stage cervical cancer group were higher than those in the disease control and the healthy control groups (p < 0.05). The levels of serum HE4, CEA, and AFP were related to the FIGO stage as well as the histological grading of patients with early stage cervical cancer (p < 0.05). The results of the ROC curves revealed that the AUC areas of HE4, CEA, and AFP for single as well as triple diagnosis of patients with early stage cervical cancer were 0.725, 0.679, 0.663, and 0.811, respectively, and the AUC of the three combined tests was markedly higher than that of HE4, CEA, AFP single test (p < 0.05). LIMITATIONS: There is a lack of larger sample sizes to test whether the combined HE4, CEA, and AFP detection has sufficient validity at the individual level and there are not enough serum samples in this study to perform circulating HPV-DNA detection and compare it with the levels of serum markers. CONCLUSION: The combination of HE4, CEA, and AFP has good clinical reference value analysis in the auxiliary diagnosis of early stage cervical cancer, and it is worthy of further validation and popularization.

A label-free and signal-amplifiable fluorescent biosensor based on aptamer-conjugated gold nanoparticles and hybridization chain reaction for determination of carcinoembryonic antigen.

The sensitive detection of cancer biomarkers is crucial for early accurate diagnostics and therapy of cancer patients. Carcinoembryonic antigen (CEA) is a tumor-associated antigen derived from colon cancer and embryonic tissues. In this study, we have developed a label-free fluorescence biosensing platform for the quantification of CEA with the "turn-on" signal output. This platform employs a label-free strategy that incorporates an aptamer-modified gold nanoparticle (Apt@AuNP) probe for the recognition of CEA, in combination with hybridization chain reaction (HCR) amplification. In the presence of target CEA, Apt@AuNPs selectively capture CEA, resulting in a reduction of subsequent complementary chains (CP) binding on Apt@AuNPs. The remaining CP, acting as the initiator sequence for HCR, triggers the HCR, leading to the formation of abundant G-quadruplex structures. By employing Thioflavin T (ThT) for the formation of G-quadruplex/ThT complexes, the biosensor exhibits a significant enhancement of the fluorescence signal. Under optimized conditions, the biosensor platform demonstrates a limit of detection of 0.03 nM and a linear range from 0.1 to 2.5 nM. Additionally, the specificity investigation reveals the high selectivity of this fluorescent biosensor. Finally, the performance of this method has been validated by successfully detecting CEA in real-life samples, highlighting its potential for clinical applications.

Clinical utility of the carcinoembryonic antigen level in patients with stage III colon cancer after surgery and adjuvant chemotherapy.

PURPOSE: The association between perioperative and post-adjuvant carcinoembryonic antigen (CEA) levels and recurrence and prognosis remains unclear. We aimed to evaluate whether perioperative CEA levels are an integral component of the assessment of recurrence and prognosis of patients with stage III colon cancer (CC). METHODS: This retrospective study was conducted at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research from 2005 to 2013. We enrolled patients with stage III CC who underwent complete resection of a primary tumor and received adjuvant chemotherapy. We analyzed the association between perioperative and post-adjuvant CEA levels and recurrence-free survival (RFS) and overall survival (OS). RESULTS: A total of 564 consecutive patients were included in the analysis. The RFS and OS of patients with high postoperative CEA levels were significantly worse than those of patients with normal postoperative CEA levels. In the multivariate analysis, high postoperative CEA levels were associated with shorter RFS and OS. The number of risk factors, postoperative CEA levels, and T/N-stage all had a cumulative effect on RFS and OS. CONCLUSIONS: High postoperative CEA levels and the number of risk factors are associated with recurrence and worse prognosis for patients with stage III CC.

Prognostic value of carcinoembryonic antigen (CEA) and CA 19-9 levels in patients with obstructive colorectal cancer treated with a self-expandable metallic stent and curative surgery.

PURPOSE: The importance of tumor markers is well established; yet little is known about their prognostic value for patients with obstructive colorectal cancer (OCRC). We investigated the clinical significance of carcinoembryonic antigen (CEA) and CA 19-9 levels in patients with non-metastatic OCRC, who underwent insertion of a self-expandable metallic stent and curative surgery. METHODS: Clinical data on 91 patients with OCRC were analyzed retrospectively to evaluate the associations of preoperative serum values of tumor makers with short- and long-term outcomes. RESULTS: The 91 patients comprised 53 men and 38 women, with a median age of 71 years. Twelve patients had an elevated preoperative CA 19-9 level. Multivariate analyses revealed that an elevated CA 19-9 level was independently associated with poor disease-free survival (DFS) [hazard ratio (HR) = 4.57, 95% confidence interval (CI) 2.06-10.14, P < 0.001] and overall survival (HR = 4.06, 95% CI 1.46-11.24, P = 0.007). A CEA level > 5 ng/ml had no prognostic value, whereas a CEA level > 10.8 ng/ml was significantly associated with worse DFS (P = 0.032). CONCLUSION: Measuring the CA 19-9 level concomitantly with the CEA level for patients with advanced CRC, including OCRC, may provide a valuable means to improve prognostication.

Prognostic impact of pre- and postoperative tumor markers in patients with intrahepatic cholangiocarcinoma.

PURPOSE: The present study assessed the impact of pre- and postoperative tumor markers on the survival of patients with intrahepatic cholangiocarcinoma. METHODS: Medical records of 73 patients with intrahepatic cholangiocarcinoma were reviewed retrospectively. The pre- and postoperative carcinoembryonic antigen and carbohydrate antigen 19-9 levels were assessed. Patient characteristics, clinicopathological factors, and prognostic factors were analyzed. RESULTS: The median recurrence-free survival and overall survival were 30.0 and 90.9 months, respectively. A multivariate survival analysis revealed that elevated postoperative carbohydrate antigen 19-9 (p = 0.023) was the only independent poor prognostic factor. The median overall survival of patients with normal and elevated postoperative carbohydrate antigen 19-9 levels was 101.4 and 15.7 months (p < 0.001), respectively. Multivariate logistic regression identified elevated preoperative carbohydrate antigen 19-9 as an independent preoperative risk factor for elevated postoperative carbohydrate antigen 19-9. The optimal cutoff value of preoperative carbohydrate antigen 19-9 for predicting elevated postoperative carbohydrate antigen 19-9 was 40 U/mL, with a sensitivity and specificity of 92% and 87%, respectively (area under curve = 0.915). CONCLUSIONS: Elevated postoperative carbohydrate antigen 19-9 was an independent poor prognostic factor. Preoperative predictors, such as elevated preoperative carbohydrate antigen 19-9, may indicate the need for neoadjuvant therapies to improve the survival.

Near-infrared light-enhanced colorimetric signal amplification strategy for tumor marker detection based on MoS2/CuO/Au nanocomposite.

A novel signal amplification strategy was developed by combining near-infrared light with MoS2/CuO/Au nanocomposite for building a colorimetric immunoassay. First, MoS2/CuO/Au nanocomposite was synthesized by precipitation and photoreduction methods and characterized by scanning electron microscopy (SEM) and X-ray powder diffraction (XRD). MoS2/CuO/Au nanocomposite has oxidase-like activity and can oxidize TMB to form a blue product (TMBox). Further, the catalytic oxidation of TMB was accelerated under near-infrared (NIR) laser radiation. The sandwich-type colorimetric immunoassay was constructed using MoS2/CuO/Au nanocomposite. Under the enhancement of near-infrared light, carcinoembryonic antigen (CEA) was sensitively detected in the range 0.1 to 40 ng/mL with the limit of detection of 0.03 ng/mL. Moreover, the immunosensor has excellent selectivity and anti-interference, good repeatability, and stability.

Rapid photothermal assay for ultrasensitive point-of-care detection of tumor markers based on a filter membrane.

An ultrasensitive photothermal assay was designed for point-of-care testing (POCT) of tumor markers based on a filter membrane. Firstly, Cu2-xSe was successfully encapsulated in liposome spheres with biotin on the surface and connected to carcinoembryonic antigen (CEA) aptamer with 3'end modified biotin by streptavidin. Secondly, the CEA antibody was successfully modified on the surface of the nitrocellulose membrane through simple incubation. Finally, the assay process was completed using a disposable syringe, and the temperature was recorded using a handheld infrared temperature detector. In the range 0-50 ng mL-1, the temperature change of the nitrocellulose membrane has a strong linear relationship with CEA concentration, and the detection limit is 0.097 ng mL-1. It is worth noting that the entire testing process can be easily performed in 10 min, much shorter than traditional clinical methods. In addition, this method was successfully applied to the quantitative determination of CEA levels in human serum samples with a recovery of 96.2-103.3%. This rapid assay can be performed by "one suction and one push" through a disposable syringe, which is simple to operate, and the excellent sensitivity reveals the great potential of the proposed strategy in the POCT of tumor biomarkers.

Single-atom iron boosts electrochemiluminescence for ultrasensitive carcinoembryonic antigen detection.

A simple and ultrasensitive sandwich-type electrochemiluminescence (ECL) immunosensor has been developed using porous three-dimensional gold nanoparticles (Au NPs) iron(Fe)-zinc(Zn) metal-organic frameworks (Au NPs-FeZn-MOFs@luminol) as high-efficiency ECL signal probes with Fe single-atom catalysts (SACs) (Fe-N-C SACs) as potentially advanced coreaction accelerators and dissolved oxygen as a coreaction agent to realize an H2O2-free amplification method for detecting carcinoembryonic antigen (CEA). The cathodic ECL of luminol, which was usually negligible, increased first. Because the Fe-N-C SACs exhibited an outstanding catalytic performance and a unique electronic structure, different reactive oxygen species (ROS) were generated via the oxygen reduction reaction. ROS oxidized the luminol anions to luminol anion radicals, preventing the time-consuming luminol electrochemical oxidation. Furthermore, the luminol anion radicals generated in situ reacted with ROS to produce potent cathodic ECL emissions. The immunosensor exhibited favorable analytical accuracy (detection range: 0.1 pg mL-1 - 80 ng mL-1), and its detection limit for serum samples was 0.031 pg mL-1 (S/N = 3). Consequently, the proposed strategy offers a new approach for early screening of CEA.

Construction of electrochemical immunosensor from MXene/multi-walled carbon nanotubes/gold nanoparticles for specific detection of carcinoembryonic antigen.

With the advancement of nanotechnology, various types of nanomaterials have been integrated into electrochemical immunoelectrodes to enhance their performance. Among these, MXene stands out as a promising candidate due to its high electron transfer capacity and abundant surface chemical groups. However, the improvement in electrode performance is often hindered by the self-restacking and agglomeration of MXene. To address this issue, multi-walled carbon nanotubes (MWCNTs) were selected to form composites with MXene. Subsequently, a label-free immunosensor, BSA/Ab/AuNPs/MXene-MWCNTs-Nafion/ITO, was fabricated for specific detection of carcinoembryonic antigen (CEA), a widely used tumor marker. The results demonstrated that the incorporation of MWCNTs can effectively prevent the self-stacking of MXene. Moreover, the composites enhanced the loading of gold nanoparticles (AuNPs) to connect the antibodies, thereby improving electronic transmission signals and sensitivity. The sensor exhibited excellent analytical performance towards CEA with a wide linear range (0.050 to 200 ng mL-1) and a low limit of detection of 0.015 ng mL-1 (S/N = 3). The possibility of it being applied in clinical trials was verified by using ELISA and differential pulse voltammetry (DPV) assays to detect CEA in serum samples. The recoveries ranged from 95.34 to 102.09% with relative standard deviations (RSDs) below 5.00%. Furthermore, the sensor displayed satisfactory selectivity, repeatability, and stability. We hope the findings highlight promising prospects for advanced immunosensor development and alternative strategies in cancer diagnosis.