Highly sensitive chemiluminescence immunoassay utilizing functionalized magnetic metal-organic framework materials for the detection of CEA and CA199.

Simultaneous quantitative detection of multiple tumor markers with a rapid and sensitive multicolor quantum dots based immunochromatographic test strip

Simultaneous, rapid, and quantitative detection of multiple tumor markers is extremely important for the prevention and early diagnosis of cancers. In this study, we established a microfluidic-based indirect competitive chemiluminescence enzyme immunoassay for simultaneous detection of cancer antigen 15-3 (CA15-3) and progesterone receptor membrane components 1 (PGRMC1) for diagnosis of breast cancer. CA15-3 and PGRMC1 could be simultaneously detected on the chip. On the chip, the linear ranges of CA15-3 and PGRMC1 were 10 pg/mL–100 ng/mL and 20 pg/mL–358 ng/mL, respectively, whereas the limits of detection (LOD) of CA15-3 and PGRMC1 were 3 pg/mL and 5 pg/mL, respectively. Compared with the enzyme-linked immunosorbent assay (ELISA, LOD = 20 pg/mL for CA15-3; LOD = 10 pg/mL for PGRMC1), our method could simultaneously detect multiple samples with higher sensitivity, which could greatly improve the detection efficiency and meet the requirement for early diagnosis of breast cancer.

Multiplex detection of tumor markers in blood with high specificity and high sensitivity is critical to cancer diagnosis, treatment, and prognosis. Herein, we demonstrate a strategy for simultaneous detection of multiple tumor markers in blood by functional liquid crystal (LC) sensors assisted with target-induced dissociation (TID) of an aptamer for the first time. Magnetic beads (MBs) coated with an aptamer (apt1) are employed to specifically capture target proteins in blood. After incubation of the obtained protein-coated MBs with duplexes of another aptamer (apt2) and signal DNA, sandwich complexes of apt1/protein/apt2 are formed on the MBs due to specific recognition of target proteins by apt2, which induces release of signal DNA into the aqueous solution. Subsequently, signal DNA is specifically recognized by highly sensitive DNA-laden LC sensors. Using this strategy, a 3D printed optical cell was employed to enable simultaneous detection of multiple tumor markers such as carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and prostate specific antigen (PSA) with high specificity and high sensitivity. Overall, this effective and low-cost multiplex approach takes advantage of the easy separation of MBs, high specificity of aptamer-based recognition, and high sensitivity of functional LC sensors. Plus, it offers a performance that is competitive to that of commercial ELISA kits without potential interference from hemolysis, which makes it very promising in multiplex detection of tumor markers in clinical applications.

Electrochemical sensor for the simultaneous detection of CA72-4 and CA19-9 tumor markers using dual recognition via glycosyl imprinting and lectin-specific binding for accurate diagnosis of gastric cancer

A sandwich-type electrochemical immunosensor for ultrasensitive detection of multiple tumor markers using an electrical signal difference strategy

BACKGROUNDEarly diagnosis of colorectal cancer (CRC) is of great significance to improve the survival rate and quality of life of patients, but early diagnosis of CRC requires more sensitive techniques. Peripheral blood UL16-binding protein 2 (ULBP2) and human fibrinogen degradation products (DR-70) are the main indicators for the diagnosis of malignant tumors.AIMTo assess ULBP2 and DR-70 potential for the early diagnosis and prognostic evaluation of CRC to provide a reference.METHODSThis study involved 60 patients with early-stage CRC (CRC group), 50 patients with benign colorectal tumors (benign group), and 50 healthy patients (control group) enrolled at the Affiliated Hospital of Jiangnan University and Jiangsu Province Official Hospital between January, 2020 and January, 2022. ULBP2 and DR-70 levels in the blood were determined and differences among the three groups and early diagnostic values for CRC were determined. Patients with CRC were divided into the good prognosis and poor prognosis groups, and ULBP2 and DR-70 levels in the blood and diagnostic values were compared.RESULTSULBP2 and DR-70 serum levels were significantly higher in the CRC group than in the control and benign groups (P < 0.05); however, no significant differences were observed between the benign and control groups (P > 0.05). Among the 60 patients with CRC followed up for two years, two died (3.33%) and 15 exhibited tumor metastasis, progression, or recurrence (25.00%). ULBP2 and DR-70 serum levels were significantly higher in the poor prognosis group than in the good prognosis group (P < 0.05). A receiver operating characteristic curve was plotted. Area under the curve, sensitivity, and specificity of serum ULBP2 with DR-70 for the early diagnosis of CRC were higher than those of the single serum indices (P < 0.05) in both the good and poor prognosis groups.CONCLUSIONULBP2 and DR-70 serum levels were significantly high in patients with early-stage CRC. They improved the diagnostic rate of early-stage CRC and predicted patient prognosis, thereby showing clinical application potential.

尽管目前结直肠癌治疗方法不断的创新与发展，其预后仍然较差，尤其是晚期结直肠癌，如病人可以早期诊断并治疗其5年生存率可以显著提高。结直肠癌不仅影响人均寿命，也对社会经济造成巨大负担。传统结直肠癌筛查方法包括便潜血检测及结肠镜检查，便潜血检测其敏感性及特异性较低；而结肠镜具有侵入性，花费较高且存在一定风险。这两项方法并不能满足结直肠癌早期诊断的要求，因此迫切需要一种筛查方法早期发现、早期诊断结直肠癌，延长结直肠癌患者生存期，改善其预后。继基因组学、转录组学、蛋白质组学之后新兴的一门“组学”称为代谢组学，其对生物体内参与生化反应成千上万中间产物及终产物进行动态的定性定量分析，可以反应生物不同生理、病理及生长状态。近期研究发现代谢组学在肿瘤的研究中具有广泛的用途，包括肿瘤早期诊断、分期、评估疗效和预测预后等，其中包括关于结直肠癌的研究，这为建立有效、稳点、可靠的结直肠癌早期诊断方法提供了新的思路。本文对代谢组学在结直肠癌中早期诊断的研究进展作一综述。 Although the treatment methods of colorectal cancer have experienced constant innovations and development, the prognosis remains poor, especially among patients with advanced colorectal can-cer. Early diagnosis and treatment may significantly improve the five-year survival rate of these pa-tients. Colorectal cancer not only shortens mean life span, but also percolates the social economy. Traditional screening methods of colorectal cancer mainly include fecal occult blood detection and colonoscopy. Fecal occult blood detection focuses on the sensitivity of colerectal cancer but has low specificity, while colonoscopy is invasive, expensive and subject to some risk. These two methods fail to meet the requirements for early diagnosis of colorectal cancer. Therefore, there is an urgent need for a screening method for early detection and early diagnosis of colorectal cancer in order to prolong the survival time of patients with colorectal cancer and improve the prognosis. Following genomics, transcriptomics and proteomics, metabolomics comes into being as a new “omics” that carries out dynamic, quantitative and qualitative analyses of thousands of intermediate products and end products entering into a sequence of biochemical reactions, thus reflecting various physiological, pathological and growth statuses. Recent studies have found that metabolomics had a wide range of uses in cancer researches, including early tumor diagnosis, staging, therapeutic evaluation, prognosis prediction and so on; researchers on colorectal cancer also included. This provides new ways for establishing effective, stable and reliable methods of early diagnosis of colorectal cancer. This review mainly presents an introduction to the concept and research techniques of metabolomics, as well as advances in its applications in early diagnosis of colorectal cancer.

Establishment of apoptotic regulatory network for genetic markers of colorectal cancer

Objective To investigate the value of detection of 6 tumor markers: neuronspecific enolase(NSE), cytokeratin fragment 21-1(CYFRA21-1), carbohydrate antigen 125(CA125), carcinoembryonic antigen(CEA), Tumor Specific Growth Factor(TSGF) and squamous cell carcinoma antigen(SCC) in the clinical diagnosis of lung cancer. Methods From July 2013 to July 2014, 174 blood samples were collected from 76 lung cancer patients, 50 lung benign disease patients and 48 healthy controls.All the blood sample were detected for 6 tumor markers mentioned above by Immune chemiluminescence technique. Results Lung cancer patients have higher levels of 6 tumor markers than healthy controls(P<0.005) and have higher levels of 5 tumor markers except CA125 than patients with benign lung diseases(P<0.05). Among lung cancer patients, levels of 6 tumor markers were compared by 3 types of lung cancer as lung squamous cell carcinoma, lung adenocarcinoma and small cell carcinoma. Patients with lung squamous cell carcinoma have higher levels of SCC and CYFRA21-1 than patients with other two types(P<0.05, P<0.01). Patients with lung adenocarcinoma have higher levels of CA125 and CEA than patients with other two types (both P<0.01). Patients with small cell carcinoma had the highest level of NSE(P<0.05). No significant differences of TSGF level were observed among the 3 types of lung cancer. Conclusion The combined detection of multiple tumor markers is very useful in the diagnosis of lung cancer and in the pathologic classification and better than single assay. Key words: Lung cancer; Tumor marker

Colorectal adenomas and early cancers are grossly classified into three groups: protruded, flush or slightly elevated (so-called flat adenomas), and depressed. Protruded lesions and flat adenomas are not invasive until they are rather large, whereas depressed lesions can invade the submucosa even when very small. It is not difficult to detect protruded and flat adenomas, but depressed carcinomas are often overlooked. Keys to the detection of depressed carcinomas are a slight color change, bleeding spots, interruptions of the capillary network pattern, slight deformation of the colonic wall, shape change of the lesion with insufflation and deflation of air, and interruption of the innominate grooves by the lesion. Spraying of indigo carmine dye helps to clarify the lesions. Pit pattern analysis with magnifying colonoscopy is useful for diagnosis of early colorectal cancer. Pit pattern analysis and histologic examination suggest that depressed carcinomas probably have arisen de novo, without going through an adenomatous step. Some adenomas appear at first to have a depression, but such cancer-mimicking adenomas with pseudodepression must be distinguished from depressed carcinomas because they are quite different in nature. Protruded and flat adenomas can usually be removed with polypectomy or hot biopsy techniques. Depressed carcinomas are treated with an endoscopic mucosal resection (EMR) technique; but when they massively invade the submucosa, surgical resection is indicated. Some neoplastic lesions, which we call laterally spreading tumors, extensively and circumferentially spread along the colonic wall, although they are short in height. They tend to have a rather benign nature despite their large size; therefore EMR or a piecemeal EMR method is indicated.

With the growth in enrollment of Medicare patients in HMOs the effectiveness of care received by Medicare/HMO patients continues to be of concern. By considering the relationship of insurance to stage at diagnosis, this study inquires whether HMOs emphasize early diagnosis of colorectal cancer to a greater extent than FFS plans, if particular HMO types (group/nongroup models) are more successful in doing so, and how this pertains to survival. Data for 1329 Medicare patients with colorectal cancer, diagnosed 1987 to 1993, and residing in northern California, were acquired from a population-based cancer registry. Insurance included two types of Medicare HMOs (group and nongroup model) and three fee-for-service (FFS) categories: Medicare with private supplement, Medicare/Medicaid, and Medicare only. The relationships of insurance to AJCC stage at diagnosis and of insurance to survival following diagnosis were examined, respectively, with logistic regression models and survival analysis (controlling for age, ethnicity, tumor location, educational level, sex, and hospital type). Likelihood of early stage colorectal cancer was greater for Medicare patients in nongroup model HMOs or having private FFS supplements than for those in group model HMOs, Medicare/Medicaid, or Medicare alone. All-cause and colorectal cancer mortality did not differ significantly among Medicare patients with group model HMO, nongroup model HMO and private FFS supplements. Medicare/Medicaid patients experienced significantly greater all-cause mortality than private FFS patients. Differences within this study population in early stage diagnosis of colorectal cancer and breast cancer, respectively, by type of Medicare supplemental insurance may be attributable to which preventive screening measures are included in health plan report cards.

A sensitive chemiluminescence (CL) imaging immunoassay method for detection of multiple tumor markers with high throughput, easy operation, and low cost was developed. The immunosensor array was prepared by covalently immobilizing capture antibodies on corresponding sensing sites on a silanized disposable glass chip. Gold nanoparticle-based bioconjugates with a high molar ratio of horseradish peroxidase (HRP) to detection antibodies were used for signal amplification. Under a sandwich immunoassay, the CL signals triggered by HRP captured on each sensing cell were collected by a charge-coupled device for simultaneous measurement of biomarkers and combination diagnosis of certain tumors. As a proof of concept, the immunosensor array was applied to detect α-fetoprotein, carcinoma antigen 125, carbohydrate antigen 153, and carcinoembryonic antigen and to screen patients with liver, breast, or ovarian cancers. This method showed wide linear ranges over 5 orders of magnitude and much lower detection limits than previously reported multiplexed immunoassays. The high throughput and acceptable stability, reproducibility, and accuracy showed good applicability of the proposed multiplex CL imaging immunoassay in clinical diagnosis.

Correction for ‘Simultaneous and combined detection of multiple tumor markers for cancer screening in human serum by an upgraded photonic crystal-encoded suspension array’ by Shiya Zheng et al., RSC Adv., 2016, 6, 92267–92275.

Simultaneous detection of multiple tumor markers is of great significance for an accurate diagnosis and early treatment of cancer. Electrochemical homogeneous biosensing strategies have been shown to have advantages, such as high sensitivity and no electrode modification, but they are still a challenge in the field of simultaneous detection of multiple tumor markers. The ER, PR, HER2, and Ki67 proteins are the standard biomarkers for the clinical molecular typing of breast cancer. Precise, sensitive, and simultaneous detection of these four biomarkers is of great importance in the molecular typing of breast cancer, which helps in the creation of personalized treatment plans. In the present study, we developed an electrochemical homogeneous electrochemical bioplatform based on metal ions/SiO2NPs/magnetic beads for detection of the four biomarkers and simultaneous diagnosis of the 10 types of breast cancer directly in human serum at one system by a single electrode. The electrochemical bioplatform has a short detection time of 140 min; however, the current clinical tissue testing time takes about 1 week. Also, the electrochemical bioplatform selectively detects HER2, ER, Ki67, and PR in a range of 0-1000 pg/mL with detection limits of 2, 1.8, 10.36, and 1.33 pg/mL, respectively.

Aptamer induced multicoloured Au NCs-MoS2 “switch on” fluorescence resonance energy transfer biosensor for dual color simultaneous detection of multiple tumor markers by single wavelength excitation