Progress in the application of circulating tumor RNA in clinical tumor diagnosis and treatment / 中华检验医学杂志

Liquid biopsy can non-invasively reveal the status of tumors and its prognosis in vivo, which is hotspots and difficulties of research in current era. Among them, an emerging marker called circulating tumor RNA (ctRNA) reflects the genetic information of tumor origin and provides a powerful basis for early diagnosis, targeted drug monitoring and prognosis prediction. At this stage, several ctRNA kits have been approved for clinical use. For example, microRNA (miRNA) can be used for aided diagnosis of liver cancer. And many transformation applications of promising ctRNA have been vigorously carried out. Despite the facts that there are still many clinical challenges of ctRNA detection technology to be solved effectively, ctRNA, as a new member of the liquid biopsy technology, has shown remarkable clinical value. Along with the mechanism becoming gradually clear, ctRNA will be a reliable diagnostic tool with the increasing clinical requirements for facilitating the tumor management.

Progress in the application of novel liquid biopsy techniques in clinical tumor diagnosis and treatment / 中华检验医学杂志

Liquid biopsy can non-invasively reveal the status of tumors in vivo, and provides a powerful basis for early diagnosis, personalized treatment monitoring and prognosis prediction. According to the type of tumor-associated material, liquid biopsy covers circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), extracellular vesicles (EVs) and circulating tumor RNA (ctRNA) etc. At present, several liquid biopsy products havebeen approved for clinical use, while many transformation studies have been vigorously carried out. However, there are still many clinical challenges to be solved effectively. Despite the standardization of detection and quality management system of liquid biopsy are lagged with the rapid development of technology, liquid biopsy, as a highly promising detection technology, will become a reliable diagnostic tool with the increasing clinical requirements for facilitating the tumor management.

Biomarker analysis of fucosylated kininogen through depletion of lectin reactive heterophilic antibodies in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) accounts for >700,000 deaths worldwide, largely related to poor rates of diagnosis. Our previous work identified glycoproteins with increased levels of fucosylation in HCC. Plate-based assays to measure this change were compromised by increased levels of heterophilic antibodies with glycan lacking terminal galactose residues, which allowed for increased binding to the lectins used in these assays. To address this issue, we developed a multi-step protein A/G incubation and filtration method to remove the contaminating signal. However, this method was time consuming and expensive so alternative methods were desired. Herein, we describe a simple method relying on PEG precipitation that allows for the removal of IgG and IgM but retention of glycoproteins of interest. This method was tested on three sample sets, two internal and one external. PEG depletion of heterophilic IgG and IgM reduced in the coefficient of variation as observed with the protein A/G filtration method from 26.82% to 7.50% and allowed for the measurement of fucosylated protein. This method allowed for the measurement of fucosylated kininogen, which could serve as a biomarker of HCC. In conclusion, a new and simple method for the depletion of heterophilic IgG and IgM was developed and allowed for the analysis of fucosylated kininogen in patients with liver disease.

The application and prospect for the tumor marker score model in clinical diagnosis and therapy / 中华检验医学杂志

Single tumor marker(TM)for cancer diagnosis with both satisfactory sensitivity and specificity has not been found.Therefore, it is necessary to identify the biomarkers to make the TM panel and establish the corresponding multiparameter predictive model through fuzzy mathematics methods.Recent studies using the big data technology showed that the integration of the biomarkers panel and prediction score model could provide the effective and accurate diagnosis for the cancer patients and be in favor of making the scheme for personalized therapy,treatment-monitoring and prognosis prediction.A reliable and efficient TM score prediction model will provide the novel perspectives and procedures for the diagnosis and treatment of cancer patients.

Asynchronous Dissipative State Estimation for Stochastic Complex Networks With Quantized Jumping Coupling and Uncertain Measurements.

This paper addresses the problem of state estimation for a class of discrete-time stochastic complex networks with a constrained and randomly varying coupling and uncertain measurements. The randomly varying coupling is governed by a Markov chain, and the capacity constraint is handled by introducing a logarithmic quantizer. The uncertainty of measurements is modeled by a multiplicative noise. An asynchronous estimator is designed to overcome the difficulty that each node cannot access to the coupling information, and an augmented estimation error system is obtained using the Kronecker product. Sufficient conditions are established, which guarantee that the estimation error system is stochastically stable and achieves the strict (Q, S, R)-γ-dissipativity. Then, the estimator gains are derived using the linear matrix inequality method. Finally, a numerical example is provided to illustrate the effectiveness of the proposed new design techniques.

The effect of different expression levels of HER-2 on the biological characteristics of breast cancer cells / 中国癌症杂志

Background and purpose: Human epidermal growth factor receptor 2 (HER-2) is the member of tyrosine kinase receptor family. Its differential expression plays the key role in choosing targeted drug for breast cancer. This study focused on screening the breast cancer cell clones of different HER-2 expression levels, and studying the bi-ological characteristics of these cells. Methods: Breast cancer SK-BR-3 cells were clonally purified, and the expression level of soluble HER-2 (sHER-2) from the culture supernatant was detected by the ECLIA on ADVIA Centaur CP System. Cell clones with high expression (>50.0 ng/mL), medium expression (15.8-50.0 ng/mL) and low expression (<15.8 ng/mL) of sHER-2 were identified, respectively. This study observed the morphological changes of cell strains with differential expression levels of sHER-2 by cell culture. Besides, biological characteristics were compared by a series of experiments in vitro, such as clone formation, scratch assay, and transwell detection. Results: Compared with normal breast cells, sHER-2 was overexpressed significantly in SK-BR-3 breast cancer cells. Furthermore, the abilities of clone formation, mobility and invasion of sHER-2 high expression cell strain [(51.3±3.4)%, (50.0±0.6)% and (53.5±4.2)%] were signifi-cantly higher than those of sHER-2 medium expression [(42.0±3.7)%, (19.5±3.4)% and (33.2±3.9)%] or sHER-2 low expression [(26.7±2.9)%, (13.6±1.0)% and (28.9±5.4)%], and the differences were all statistically significant (P<0.05). Conclusion: Breast cancer cell strain with high expression level of sHER-2 can enhance cell proliferation, promote cell motility and other biological effects, which may lay the foundation for clinical screening of targeted drug therapies for breast cancer.

Genomic instability and its detection technologies for clinical application in cancer patients / 中华检验医学杂志

Carcinogenesis is a multistep process that a couple of genes involve in the initiation of this disease.As a pivotal hallmark of cancer, the genomic instability ensues in which genetic alterations when this process was initialized and developed. With the increasing number of studies on genomic instability, the scientists pay more attentions on its biological function at post-genomic era. Genomic instability in various carcinomas is associated with broken telomere, gene modification, and contributes to the dysfunction of DNA damage and repair pathways.This review focus on the factors involved in genomic instability, as well the current detection methods of genomic instability and their clinical application.

Diagnostic value of tumor type M2 pyruvate kinase in patients with breast cancer / 中华检验医学杂志

Objective To evaluate application value of plasma tumor type M2 pyruvate kinase (TU M2-PK) in the treatment effect monitoring in breast cancer. Methods TU M2-PK was determined by ELISA in breast cancer patients (n = 63 ), benign breast disease patients (n = 22 ) and health controls (n = 40).The receiver operation characteristic (ROC) analysis was performed as compared with CA15-3 and CEA. Results ROC analysis showed the cut-off was set at 14. 1 U/ml for TU M2-PK ( sensitivity 46. 0% ;specificity 86. 0% ), and the diagnosis efficacy of TU M2-PK was higher than CA15-3 and CEA. The level of TU M2-PK was significantly higher in breast cancer patients (13. 3 U/ml) than that in health controls (7. 2 U/ml, U = 408. 5, P < 0. 05 ) and in benign breast disease patients ( 11.1 U/ml, U = 509.0,P < 0. 05 ). With the progression of breast carcinoma, the level of TU M2-PK as well as the positivity was increased. TU M2-PK concentration was higher in patients with lymph node metastasis (23. 3 U/ml ) than those without metastasis ( 10. 9 U/ml, U = 237. 0, P < 0. 01 ). The level of TU M2-PK correlated with therapy response. An elevated level of TU M2-PK was found preclinically in recurrent disease patients, and the levels decreased in the patients, which showed sensitive to chemotherapy. The TU M2-PK level was kept at baseline in patients with stable disease. Conclusion TU M2-PK is helpful in the diagnosis of breast cancer, and it is a valuable tumor marker for disease monitoring, therapy control and prognosis evaluation in breast cancer.