Evaluation of exosomal non-coding RNAs in cancer using high-throughput sequencing

Clinical oncologists need more reliable and non-invasive diagnostic and prognostic biomarkers to follow-up cancer patients. However, the existing biomarkers are often invasive and costly, emphasizing the need for the development of biomarkers to provide convenient and precise detection. Extracellular vesicles especially exosomes have recently been the focus of translational research to develop non-invasive and reliable biomarkers for several diseases such as cancers, suggesting as a valuable source of tumor markers. Exosomes are nano-sized extracellular vesicles secreted by various living cells that can be found in all body fluids including serum, urine, saliva, cerebrospinal fluid, and ascites. Different molecular and genetic contents of their origin such as nucleic acids, proteins, lipids, and glycans in a stable form make exosomes a promising approach for various cancers’ diagnoses, prediction, and follow-up in a minimally invasive manner. Since exosomes are used by cancer cells for intercellular communication, they play a critical role in the disease process, highlighting the importance of their use as clinically relevant biomarkers. However, regardless of the advantages that exosome-based diagnostics have, they suffer from problems regarding their isolation, detection, and characterization of their contents. This study reviews the history and biogenesis of exosomes and discusses non-coding RNAs (ncRNAs) and their potential as tumor markers in different types of cancer, with a focus on next generation sequencing (NGS) as a detection method. Moreover, the advantages and challenges associated with exosome-based diagnostics are also presented.

The Application Effect of Traditional Chinese Medicine Nursing on General Anesthesia Combined with Epidural Anesthesia and Electric Resection for the Treatment of Bladder Cancer and Its Influence on Tumor Markers

Objective. To explore the effects of traditional Chinese medicine nursing on general anesthesia combined with epidural anesthesia and electric resection to treat bladder cancer and its influence on tumor markers. Methods. A total of 160 patients with non-muscle-invasive bladder cancer who underwent general anesthesia combined with epidural anesthesia and resection were included in this study. The patients were divided into control group (n = 80) and study group (n = 80) according to the random number table method. The control group received hydroxycamptothecin bladder perfusion therapy, and the study group received traditional Chinese medicine nursing combined with hydroxycamptothecin bladder perfusion therapy. The clinical efficacy, three-year cumulative survival rate, and postoperative recurrence rate of the two groups of patients were detected. The levels of tumor markers including vascular endothelial growth factor (VECF) and bladder tumor antigen (BTA) before and after treatment were also tested. The immune function, inflammatory factor levels, and quality of life of the two groups before and after treatment were evaluated. Results. The total effective rate of the study group (83.75%) was significantly higher than that of the control group (58.75%). After treatment, the serum VEGF and BTA levels, inflammatory factors interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) levels of the two groups of patients decreased, and the decrease in the study group was more significant than that in the control group P < 0.05 . After treatment, the levels of CD3+, CD4+, and CD4+/CD8+ in the two groups increased P < 0.05 , and the increase in the study group was more significant than that in the control group P < 0.05 . After treatment, the CD8+ levels of the two groups of patients decreased P < 0.05 , and the decrease in the study group was more significant than that in the control group P < 0.05 . After treatment, the quality-of-life scores in both groups increased P < 0.05 , and the increase in the study group was even more significant P < 0.05 . Conclusion. Traditional Chinese medicine nursing has significant clinical effects on the treatment of bladder cancer with general anesthesia combined with epidural anesthesia and electric resection. It can more effectively prevent the risk of recurrence of bladder cancer after surgery, significantly improve the quality of life, improve immune system function, regulate the levels of VECF and BTA, effectively reduce the level of serum inflammatory factors, inhibit tumor progression, and reduce tumor viability.

Comprehensive Assessment of Serum hsa_circ_0070354 as a Novel Diagnostic and Predictive Biomarker in Non-small Cell Lung Cancer

Background: More and more studies have shown that circular RNAs (circRNAs) play an essential role in the occurrence and development of tumors. Hence, they can be used as biomarkers to assist in diagnosing tumors. This study focuses on exploring the role of circular RNA (hsa_circ_0070354) in the diagnosis and prognosis of non-small cell lung cancer (NSCLC).Materials and Methods: First of all, high-throughput sequencing was used to find the difference in the expression of circular RNA between NSCLC and adjacent tissues. The circRNAs with higher differences in expression were selected to verify their expressions in tissues, cells, and serum using qRT-PCR. Secondly, the hsa_circ_0070354 with a significant difference was chosen as the research goal, and the molecular properties were verified by agarose gel electrophoresis and Sanger sequencing, etc. Then, actinomycin D and repeated freeze-thaw were used to explore the stability and repeatability of hsa_circ_0070354. Finally, the expression of hsa_circ_0070354 in serum of 133 patients with NSCLC and 97 normal donors was detected, and its sensitivity, specificity, and prognosis as tumor markers were statistically analyzed.Results: Hsa_circ_0070354 was highly expressed in tissues, cells, and serum of NSCLC, and it has the characteristics of sensitivity, stability, and repeatability. The ROC curve indicates that hsa_circ_0070354 is superior to conventional tumor markers in detecting NSCLC, and the combined diagnosis is of more significance in the diagnosis. The high expression of hsa_circ_0070354 is closely related to the late-stage, poor differentiation of the tumor and the short survival time of the patients, which is an independent indicator of poor prognosis.Conclusion: Hsa_circ_0070354 is not only a novel sensitive index for the diagnosis of NSCLC but also a crucial marker for bad biological behavior.

Clinical Significance of Tumor Markers for Advanced Thymic Carcinoma: A Retrospective Analysis from the NEJ023 Study

The optimal tumor marker for predicting the prognosis of advanced thymic carcinoma (ATC) remains unclear. We conducted a multi-institutional retrospective study of patients with ATC. A total of 286 patients were treated with chemotherapy. Clinicopathological information, including serum tumor markers, was evaluated to determine the overall survival (OS) and progression-free survival (PFS). The carcinoembryonic antigen, cytokeratin-19 fragment, squamous cell carcinoma (SCC) antigen, progastrin-releasing peptide, neuron-specific enolase (NSE), and alpha-fetoprotein levels were evaluated. In the Kaplan–Meier analysis, the OS was significantly shorter in the patients with elevated NSE levels than in those with normal NSE levels (median, 20.3 vs. 36.8 months; log-rank test p = 0.029; hazard ratio (HR), 1.55; 95% confidence interval (CI), 1.05–2.31 (Cox proportional hazard model)); a similar tendency regarding the PFS was observed (median, 6.4 vs. 11.0 months; log-rank test p = 0.001; HR, 2.04; 95% CI, 1.31–3.18). No significant differences in the OS and PFS were observed among the other tumor markers. In both univariate and multivariate analyses of the patients with SCC only, the NSE level was associated with the OS and PFS. Thus, the NSE level may be a prognostic tumor marker for thymic carcinoma, regardless of histology.

Diagnostic and Prognostic Significance of Serum Tumor Markers in Patients With Lung Cancer

Background: Tumor markers CEA, CYFRA21-1, NSE, proGRP, and SCC-Ag were routinely used for lung cancer. The objective of this study was to evaluate the diagnostic and prognostic value of these markers.Methods: The levels of 5 serum tumor markers were measured in 255 patients with lung cancer (44 squamous cell carcinoma, 183 adenocarcinoma, 28 small cell lung cancer), 103 patients with benign lung disease, and 120 healthy controls. The relevant clinical data of the patients were collected to analyze the expression of CEA, CYFRA21-1, NSE, proGRP, and SCC-Ag in the serum of lung cancer and their correlation with prognosis.Results: The positive rates and expression levels of CEA, CYFRA21-1, NSE, proGRP, and SCC-Ag in the lung cancer group were higher than those in patients with benign lung diseases and healthy controls. CYFRA21-1 and SCC-Ag were highly expressed in lung squamous cell carcinoma, and NSE and proGRP were highly expressed in small cell lung cancer. The expression levels of CYFRA 21-1, NSE, and proGRP in small cell lung cancer were higher than those in non-small cell lung cancer. The levels of CEA, CYFARA21-1, NSE, and proGRP were linearly correlated with the occurrence of lung cancer, while the level of SCC-Ag was not significantly correlated with the occurrence of lung cancer. What’s more, the levels of CYFAR21-1 and NSE in the death group of lung cancer patients were higher than those in the survival group.Conclusion: CEA, CYFRA21-1, NSE, proGRP, and SCC-Ag played a good role in diagnosing lung cancer. CYFRA21-1 and SCC-Ag can be used as markers for the diagnosis of squamous cell carcinoma, and NSE and proGRP can be used as markers for small cell lung cancer. Meanwhile, the combined detection of CEA, CYFARA21-1, NSE, and proGRP had the highest diagnostic accuracy for lung cancer. Furthermore, CYFAR21-1 and NSE can be used to evaluate the prognosis of lung cancer patients.

Analysis on the Effects of CT- and Ultrasound-Guided Percutaneous Transthoracic Needle Biopsy Combined with Serum CA125 and CEA on the Diagnosis of Lung Cancer

The number of patients with lung cancer is difficultly diagnosed in the early stage. The purpose of the study was to investigate the effects of CT- and ultrasound-guided percutaneous transthoracic needle biopsy combined with serum CA125 and CEA on the diagnosis of lung cancer. 120 patients with suspected lung cancer admitted to our hospital from January 2019 to January 2020 were selected and divided into an ultrasound group (n = 60) and CT group (n = 60), according to different percutaneous transthoracic needle biopsy modalities. All patients received serum tumor markers detection, so as to compare the CT- and ultrasound-guided percutaneous transthoracic needle biopsy results and pathology results, levels of serum tumor markers among all patients and the patients with different lung cancer types, and diagnostic efficacy of tumor markers, as well as complication rate (CR) in patients. The sensitivity and specificity of ultrasound-guided percutaneous transthoracic needle biopsy were 0.880 and 0.800, respectively, while those of CT-guided percutaneous transthoracic needle biopsy were 0.909 and 0.625, respectively; the CA125 and CEA levels in the lung cancer group were higher than those in the benign group ( P < 0.001 ); the CA125 and CEA levels of the patients with adenocarcinoma were higher than those with squamous carcinoma, and the CEA levels of the patients with small-cell carcinoma were lower than those with adenocarcinoma ( P < 0.05 ); the sensitivity, specificity, and Youden indexes of CA125 were 0.638, 0.833, and 0.471, respectively, while those of CEA were 0.766, 0.778, and 0.544, respectively; there were no significant differences in CR between the two groups ( P > 0.05 ). CT- and ultrasound-guided percutaneous transthoracic needle biopsy is a safe and feasible diagnostic modality for lung cancer, and its combination with serum CA125 and CEA can significantly improve the accuracy of the detection results, which is worthy of promotion and application in clinical practice.

MARCADORES TUMORALES PRONÓSTICOS EN CÁNCER DE MAMA: BAX y Bcl-2

Introducción: El carcinoma de mama representa el 16% de todos los cánceres femeninos, cada año en las Américas, más de 462,000 mujeres son diagnosticadas y casi 100,000 mueren por esta causa, por lo que la detección de nuevos marcadores pronósticos se hace imprescindible para el desarrollo de nuevas terapias oncológicas. Objetivo: Identificar los marcadores tumorales con fines pronósticos en cáncer de mama en células de cultivo de carcinoma de mama MCF7. Método: Se desarrolló un estudio explicativo longitudinal y prospectivo observacional para identificar marcadores tumorales con valor pronóstico en modelos celulares MCF7 de Cáncer de Mama, se utilizarán métodos estadísticos descriptivos e inferenciales. Resultados: Se identificó un predominio de Bcl-2 en las células de cultivo MCF7 de Carcinoma de Mama. Conclusión: La identificación de BAX y Bcl-2 en modelos celulares MCF 7 de Carcinoma de Mama permite evaluar nuevas opciones terapéuticas relacionadas con la inducción de la apoptosis. La predominancia Bcl-2 pudiera constituir un factor de mal pronóstico y menor supervivencia debido a su efecto inhibidor de la apoptosis, donde subyacen alteraciones mitocondriales, que inciden en la regulación del nivel de calcio intracelular, o por su efecto antioxidante. Palabras clave: Neoplasias de la mama, Pronóstico, Apoptosis, Proteína de Susceptibilidad a Apoptosis Celular ABSTRACT Introduction: Breast carcinoma represents 16% of all female cancers, each year in the Americas, more than 462,000 women are diagnosed and almost 100,000 die from this cause, so the detection of new prognostic markers is essential for the development of new oncological therapies. Objective: To identify tumor markers for prognostic purposes in breast cancer in MCF7 breast carcinoma culture cells. Method: A longitudinal and prospective observational explanatory study was developed to identify tumor markers with prognostic value in MCF7 cell models of Breast Cancer, descriptive and inferential statistical methods will be used. Results: A predominance of Bcl-2 was identified in the MCF7 culture cells of Breast Carcinoma. Conclusion: The identification of BAX and Bcl-2 in MCF 7 cell models of Breast Carcinoma allows to evaluate new therapeutic options related to the induction of apoptosis. The Predominance bcl-2 could constitute a factor of poor prognosis and lower survival due to its inhibitory effect of apoptosis, where mitochondrial alterations underlie, which affect the regulation of the level of intracellular calcium, or for its antioxidant effect. Keywords: Breast Neoplasms, Prognosis, Apoptosis, Cellular Apoptosis Susceptibility Protein

Optical cytosensors for detection of circulating tumour cells

Blood analysis is an established approach to monitor various diseases, ranging from heart defects and diabetes to cancer. Among various tumor markers in the blood, circulating tumor cells (CTCs) have...

The Significance of Serum Tumor Markers CEA, CA19-9, CA125, CA15-3 And AFP in Patients Scheduled for Orthotopic Liver Transplantation: Do Elevated Levels Really Mean Malignancy?

AIM AND BACKGROUND: Preparation of the patients for liver transplantation is a meticulous process and includes evaluation of tumor markers to rule out occult malignancy. Present study evaluated the significance of serum tumor markers in patients bound for liver transplantation due to viral and other etiologies of liver failure.PATIENTS AND METHODS: 381 patientswho underwent liver transplantation were included in the study. Demographic data, Model for End stage.Liver Disease (MELD) scores and serum tumor marker levels were prospectively collected.RESULTS: AFP levels were significantly higher in viral etiologies when compared to other etiologies (p<0.05).Ca 19-9 was significantly higher in viral etiologies (p<0.05). Among the viral etiologies HCV related liver failure had higher carcinoembryonic antigen (CEA) and Carbohydrate antigen 19-9 (Ca 19-9) levels (p<0.05). A correlation was found between increasing MELD scores and serum levels of tumor markers (p<0.05)CONCLUSIONS: Tumor markers such as AFP, CEA, Ca 125 and Ca 19-9 can be elevated in end stage liver disease. Their levels vary according to etiology and severity of disease. The diagnostic capabilities of these markers are reduced in end stage liver disease setting but they contribute to the evaluation of the pathophysiology of chronic liver disease. Transplantation can be performed safely in cases with high tumor marker levels provided that any occult malignancy is ruled out by means of imaging and endoscopic techniques. Tumor markers can guide the physician in determining the severity of liver cirrhosis and further studies are needed to validate such a relationship.

THE ROLE OF IMMUNOHISTOCHEMICAL MARKERS IN PREDICTING RECURRENCE OR DEATH IN PATIENTS WITH MEDULAR THYROID CANCER

Introduction. Medullary thyroid cancer (MTC) belongs to a class of rare neuroendocrine aggressive tumors and arises from parafollicular cells (C-cells). An important modern problem is the development of ways to predict the recurrence of this disease. The aim of the study is to determine the role of immunohistochemical tumor markers of medullary thyroid cancer in predicting recurrence or death. Materials and methods. The analysis of the prospective study included 22 patients with MTC, 5 of whom have developed a recurrence and 4 have died at the end of the 10-year (120 months) follow-up period. Immunohistochemical examinations were performed using monoclonal antibodies of tumor markers calcitonin, chromogranin A, vimentin and Ki-67. Results. The discrepancy between the data of histological and immunohistochemical examinations in MTC is 12.0%, which indicates the hyperdiagnosis of this nosology and argues the importance of performing immunohistochemical examinations to verify the diagnosis. Patients who had a recurrence of MTC had significantly (p <0.05) lower levels of calcitonin expression (5.00 [5.00; 5.00] points) compared with patients who did not relapse, where this figure was 6.00 [6.00; 7.00] points. In patients with MTC, an increase in calcitonin expression was significantly associated with an increase in chromogranin A expression (r = + 0.49, p = 0.02); a similar relationship was found for the proportions of immunopositive cells of these tumor markers: r = + 0.68, p = 0.001. At the same time, it was found that the increase in the level of calcitonin expression was apparently combined with the decrease in the level of Ki-67 expression (r = -0.52, p = 0.02). It was also found that the increase in the level of vimentin expression is combined with an increase in the expression (r = + 0.64, p = 0.001) and the proportion of immunopositive cells of chromogranin A (r = + 0.45, p = 0.038). Conclusions. Low levels of calcitonin expression are prognostically unfavorable markers for the recurrence of MTC. Specific tumor markers are important in the treatment process and for the dynamic monitoring of patients with MTC.