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Objective:To evaluate the clinical radiological features combined with circulating tumor cells in the diagnosis of benign and malignant pulmonary solid nodules.Methods:Clinical data of 437 patients from Shanghai Pulmonary Hospital(SPH cohort) from January to April 2021 and 82 patients from Lanzhou University First Hospital (LZH cohort) from August 2019 to May 2022 were retrospectively included. Patients in Shanghai pulmonary hospital were randomly divided into training set and internal validation set in a ratio of 4∶1 by random number table method and patients in Lanzhou University First Hospital were as external validation set. Independent risk factors were selected by regression analysis of training set constructed a Nomogram prediction model. The performance of the Nomogram prediction model was estimated by applying receiver operating curve( ROC) analysis, tested in different nodules size and intermediate risk IPSNs and tested by calibration curve. Results:Independent risk factors selected by regression analysis for solid pulmonary nodules were age, the level of CTC, pleural Indentation, lobulation, spiculation. The Nomogram prediction mode provided an area under ROC( AUC) of 0.888, 0.833 in internal validation set and external validation set, outperforming radiological features model(0.835, P=0.007; 0.804, P=0.043) Mayo clinical model(0.781, P=0.019; 0.726, P=0.033) and CTCs(0.699, P=0.002; 0.648, P=0.012) in both two validation sets, C-index of 0.888, 0.871 and corrected C-index of 0.853, 0.842 in both two validation sets . The AUC of the prediction model with internal validation set was 0.905 and 0.871 for nodule diameter of 5-20 mm and intermediate risk probability. Conclusion:The prediction model in this study has better diagnostic value and practicability, and is more effective in clinical diagnosis of diseases.
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The amount of circulating tumor cells(CTC) in peripheral blood is very small, which is difficult to isolate. Microfluidic chips are becoming a hot area in recent years because of their portability, high sensitivity, high capture,and low cost. Microfluidic devices have been shown to maintain optimal performance for CTC isolation capture, including flux, purity, recovery, and clinical relevance. However, microfluidic technology is still unable to recover CTC with high recovery and purity.
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Neuroblastoma (NB) is the most common extracranial solid tumor in children and has the features of high recurrence rate and low survival rate, and therefore, early diagnosis, treatment response evaluation, and recurrence monitoring are of great significance for NB patients. Liquid biopsy refers to the detection of cells and nucleic acids in fluid specimens, mainly blood. It is noninvasive and can overcome tumor heterogeneity, thus making it possible to achieve the early diagnosis and dynamic detection of NB. This review introduces the latest advances in clinical research on the application of liquid biopsy in NB.
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Criança , Humanos , Biópsia Líquida , Neuroblastoma/diagnósticoRESUMO
Objective:To investigate the application value of peripheral blood circulating tumor cell (CTC) classification in the prediction of preoperative microvascular invasion of hepato-cellular carcinoma (HCC).Methods:The retrospective case-control study was conducted. The clinico-pathological data of 102 HCC patients who were admitted to Zhengzhou University People's Hospital from September 2018 to September 2020 were collected. There were 71 males and 31 females, aged from 29 to 80 years, with a median age of 57 years. Observation indicators: (1) surgical situations; (2) results of CTC detection and microvascular invasion in HCC patients; (3) results of CTC classification and the best cut-off value of CTC classification in the prediction of microvascular invasion in HCC; (4) influencing factors for microvascular invasion in HCC; (5) comparison of clinicopathological features in HCC patients with different cell counts in mesenchymal phenotype of CTC (M-CTC). Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and comparison between groups was analyzed using the nonparametric rank sum U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. The receiver operating characteristic (ROC) curve was used to determine the best cut-off value for the risk of microvascular invasion in patients. Univariate and multivariate analysis were performed using the Logistic regression model. Results:(1) Surgical situations. All 102 patients underwent surgery successfully, including 17 cases undergoing local hepatectomy, 43 cases under-going segmentectomy, 22 cases undergoing hepatic lobectomy, 13 cases undergoing hemilectomy and 7 cases undergoing enlarged hemilectomy. The operation time and the volume of intraoperative blood loss were 235(147,293)minutes and 300(110,500)mL of the 102 patients, respectively. (2) Results of CTC detection and microvascular invasion in HCC patients. Of 102 patients, there were 36 casas with epithelial phenotype of CTC (E-CTC), 86 cases with hybrid phenotype of CTC (H-CTC), 30 cases with M-CTC, respectively, and the total CTC (T-CTC) were positive in 89 cases. Results of postoperative pathological examination showed that there were 40 cases with micro-vascular inva-sion and 62 cases without microvascular invasion in the 102 patients. Of the 40 patients with micro-vascular invasion, the count of E-CTC, H-CTC, M-CTC and T-CTC were 0(0,1) per 5 mL, 4(2,5) per 5 mL, 1(0,2) per 5 mL and 5(3,8) per 5mL, respectively. The above indicators of the 62 cases without microvascular invasion were 0(0,1) per 5 mL, 3(1,5) per 5 mL, 0(0,0) per 5 mL and 3(2,6) per 5 mL, respectively. There were significant differences in the count of M-CTC and T-CTC between patients with and without microvascular invasion ( Z=-4.83, -2.96, P<0.05). (3) Results of CTC classi-fication and the best cut-off value of CTC classification in the prediction of microvascular invasion in HCC. The ROC curve showed that best cut-off value of M-CTC and T-CTC counts in the prediction of microvascular invasion in HCC were 1 per 5 mL and 4 per 5 mL, respectively, with the area under curve, the corresponding specificity, sensitivity were 0.70 (95% confidence interval as 0.60-0.81, P<0.05), 75.8%, 62.9% and 0.67 (95% confidence interval as 0.57-0.78, P<0.05), 60.0%, 72.5%, respec-tively. (4) Influencing factors for microvascular invasion in HCC. Result of univariate analysis showed that alpha fetoprotein (AFP), aspartate aminotransferase (AST), tumor diameter, tumor number, tumor margin, Barcelona clinic liver cancer staging, M-CTC counts and T-CTC counts were related factors influencing microvascular invasion in HCC ( odds ratio=3.13, 0.43, 4.92, 5.65, 2.54, 2.93, 8.25, 4.47, 95% confidence interval as 1.34-7.33, 0.19-0.98, 2.09-11.58, 2.35-13.63, 1.13-5.75, 1.27-6.74, 3.13-21.75, 1.88-10.61, P<0.05). Result of multivariate analysis showed that tumor diameter >5 cm, tumor number as multiple and M-CTC counts ≥1 per 5 mL were independent risk factors influencing microvascular invasion in HCC ( odds ratio=2.97, 4.14, 4.36, 95% c onfidence interval as 1.01-8.70, 1.14-15.02, 1.36-13.97, P<0.05). (5) Comparison of clinicopathological features in HCC patients with different cell counts in M-CTC. The 102 HCC patients were divided into the high M-CTC group of 30 cases with M-CTC counts ≥1 per 5 mL and the low M-CTC group of 72 cases with M-CTC counts <1 per 5 mL, according to the best cut-off value of M-CTC counts. Cases with hepatitis, cases with AFP >400 μg/L, cases with AST >35 U/L, cases with irregular tumor margin, cases with tumor diameter >5 cm, cases with tumor number as multiple and cases with micro-vascular invasion were 22, 17, 13, 21, 18, 16 and 22 in the high M-CTC group of 30 cases. The above indicators were 35, 18, 48, 26, 25, 21 and 18 in the low M-CTC group of 72 cases. There were significant differences in the above indicators between the high M-CTC group and the low M-CTC group ( χ2=5.25, 9.42, 4.80, 9.79, 5.55, 5.35, 20.75, P<0.05). Conclusions:The epithelial-mesen-chymal phenotype of peripheral blood CTC can be used to predict the preoperative microvascular invasion in HCC. Tumor diameter >5 cm, tumor number as multiple and M-CTC counts ≥1 per 5 mL are independent risk factors influencing microvascular invasion in HCC patients.
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In recent years, with the in-depth study of PD-1 and PD-L1 and the development of immunotherapy, the first problem is how to screen the beneficiaries. Recent clinical studies have shown that the expression level of PD-L1 in circulating tumor cells (CTC) can be used as a potential biomarker to play a guiding role in immunotherapy of malignant tumors. This article reviews the latest clinical research progress on the expression of PD-L1 in circulating tumor cells in various solid tumors.
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Tumor metastasis is an important cause of death in tumor patients. Once metastasis occurs, cancer will become more difficult to treat. Many studies have observed circulating tumor cells (CTCs) in the circulatory system of patients with metastasis. CTCs may occasionally appear in the form of clusters during the process of hematogenous metastasis. These aggregated tumor cell clusters have higher efficacy than the single CTC. The development of circulating tumor cell cluster capture technology provides new insights into tumor metastasis. The molecular mechanism of CTC clusters formation and their role in tumor hematogenous metastasis are discussed here, and their use as biomarkers and target in therapy is evaluated.
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Objective To study movement process of circulating tumor cells (CTCs) in the blood and mechanism of CTC capture by CellCollector, and reveal relationship between the detected CTC numbers and the actual CTC concentration in the body. Methods Based on Fluent and EDEM software, the unidirectional fluid-solid interaction method was applied to establish a two-phase flow model, including the hemodynamic model and the CTC transport model, and capture simulations under different CTC concentration conditions were conducted. Results The number of CTCs captured by CellCollector was significantly positively correlated with the CTC concentration in the body. When the CTC concentration was low, CTCs could only be captured in several time intervals, and the capture had a certain contingency; as the concentration increased, the uniformity of CTC capture over time became better, and the total number of captures also increased. Conclusions Through the fitting of simulation results, analytical quantitative relationship between the captured CTC number and the CTC concentration in the body is preliminarily given, which provides theoretical basis and mechanical explanation for the clinical use of CellCollector.
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@#Objective To analyze the correlation between folate receptor-positive circulating tumor cells (FR+CTC) and the benign or malignant lesions of the lung, and to establish a malignant prediction model for pulmonary neoplasm based on clinical data, imaging and FR+CTC tests. Methods A retrospective analysis was done on 1 277 patients admitted to the Affiliated Hospital of Qingdao University from September 2018 to December 2019, including 518 males and 759 females, with a median age of 57 (29-85) years. They underwent CTC examination of peripheral blood and had pathological results of pulmonary nodules and lung tumors. The patients were randomly divided into a trial group and a validation group. Univariate and multivariate analyses were performed on the data of the two groups. Then the nomogram prediction model was established and verified internally and externally. Receiver operating characteristic (ROC) curve was used to test the differentiation of the model and calibration curve was used to test the consistency of the model. Results Totally 925 patients suffered non-small cell lung cancer and 113 patients had benign diseases in the trial group; 219 patients suffered non-small cell lung cancer and 20 patients had benign diseases in the verification group. The FR+CTC in the peripheral blood of non-small cell lung cancer patients was higher than that found in the lungs of the patients who were in favorite conditions (P<0.001). Multivariate analysis showed that age≥60 years, female, FR+CTC value>8.7 FU/3 mL, positive pleural indenlation sign, nodule diameter, positive burr sign, consolidation/tumor ratio<1 were independent risk factors for benign and malignant lung tumors with a lesion diameter of ≤4 cm. Thereby, the nomogram prediction model was established. The area under the ROC curve (AUC) of the trial group was 0.918, the sensitivity was 86.36%, and the specificity was 83.19%. The AUC value of the verification group was 0.903, the sensitivity of the model was 79.45%, and the specificity was 90.00%, indicating nomogram model discrimination was efficient. The calibration curve also showed that the nomogram model calibration worked well. Conclusion FR+CTC in the peripheral blood of non-small cell lung cancer patients is higher than that found in the lungs of the patients who carry benign pulmonary diseases. The diagnostic model of clinical stage Ⅰ non-small cell lung cancer established in this study owns good accuracy and can provide a basis for clinical diagnosis.
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Circulating tumor cells (CTC) are tumor cells that escape from the primary or metastatic tumor into the circulatory system, and closely related to cancer metastasis. Since the samples can be obtained through simple and minimally invasive blood sampling operations, CTCs have a great clinical potential. PCa is one of the most common malignant tumors in men. In recent years, many scholars have conducted studies as to whether CTC technology can be used for the diagnosis and treatment of PCa, as well as for more accurate prediction of the risk of progression. This article summarizes the advances in researches relating CTC technology and the diagnosis and treatment of PCa. CTC detection has been developed from simple counting to phenotypic classification, and even to its combination with the determination of the expressions of specific genes (such as AR, AR-V7, etc.) and single-cell sequencing. Some reports showed that CTC technology has a certain significance in the early diagnosis of PCa, but its main value is demonstrated in drug sensitivity and prognosis evaluation in the late stage of the malignancy. The standardized detection methods and reference values of CTCs in PCa will be important research orientations in the near future.
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Humanos , Masculino , Contagem de Células , Segunda Neoplasia Primária , Células Neoplásicas Circulantes , Prognóstico , Neoplasias da Próstata/terapiaRESUMO
Tumor metastasis is responsible for chemotherapeutic failure and cancer-related death. Moreover, circulating tumor cell (CTC) clusters play a pivotal role in tumor metastasis. Herein, we develop cancer-specific calcium nanoregulators to suppress the generation and circulation of CTC clusters by cancer membrane-coated digoxin (DIG) and doxorubicin (DOX) co-encapsulated PLGA nanoparticles (CPDDs). CPDDs could precisely target the homologous primary tumor cells and CTC clusters in blood and lymphatic circulation. Intriguingly, CPDDs induce the accumulation of intracellular Ca
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Objective: To investigate the clinical significance and difference of peripheral blood circulating tumor cells (CTC) detection in the prognosis of patients with gastric cancer and colorectal cancer. Methods: The CTC in the peripheral blood of 32 patients with gastric cancer and 36 patients with colorectal cancer were detected by negative enrichment and imFISH technique, and the results were compared between the two groups. Results: There were 8 cases (25%) of CTC 2) were detected, and only 8 cases survived. The two groups differed significantly in survival (P=0.001). Twenty-eight cases (78%) of the patients with colorectal cancer were detected CTC 2 groups survived at the end of the follow-up. Six patients survived at the end of the follow-up. There was a significant difference between CTC 2 groups in colorectal cancer (P=0.044). The survival in gastric cancer and colorectal cancer was significantly different (P0.05). Conclusion: Negative enrichment and imFISH technique can be used to detect CTC of the peripheral blood of patients with gastric cancer and colorectal cancer. The prognosis of patients with elevated CTC is poor. It is worse in gastric cancer than in colorectal cancer.
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Morbidity and mortality rates of bladder cancer (BC) are still rising with a poor prognosis. Therefore, better biomarkers are urgently needed to advance the accurate diagnosis and treatment of BC. The limitations of the different detection techniques of circulating tumor cell (CTC) cause that the CTC as biomarkers of point of view of diagnosis and treatment of BC is not yet clear. This review first compares and analyzes the current CTC detection technology methods, and then reviews the five aspects of screening, diagnosis, staging, curative effect monitoring, prognostic evaluation, and personalized treatment of patients with malignant tumors with oncolytic virus and CTC. The application of oncolytic virus detection CTC in BC was evaluated. The results suggest that oncolytic virus with fluorescent protein combined with fluorescence microscopy and flow cytometer are used to detect CTC. This method can be only used to detect live CTCs, instead of dead CTCs. The CTC count is more accurate, efficient with high sensitivity and specificity. It can also perform phenotypic analysis of CTC and single-cell sequencing. It can be used for screening, diagnosis, and guidance of targeted therapy for bladder cancer, assessing efficacy and judging prognosis which has a very broad clinical application prospect for advancing the accurate diagnosis and treatment of BC.
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Morbidity and mortality rates of bladder cancer (BC) are still rising with a poor prognosis. Therefore, better biomarkers are urgently needed to advance the accurate diagnosis and treatment of BC. The limitations of the different detection techniques of circulating tumor cell (CTC) cause that the CTC as biomarkers of point of view of diagnosis and treatment of BC is not yet clear. This review first compares and analyzes the current CTC detection technology methods, and then reviews the five aspects of screening, diagnosis, staging, curative effect monitoring, prognostic evaluation, and personalized treatment of patients with malignant tumors with oncolytic virus and CTC. The application of oncolytic virus detection CTC in BC was evaluated. The results suggest that oncolytic virus with fluorescent protein combined with fluorescence microscopy and flow cytometer are used to detect CTC. This method can be only used to detect live CTCs, instead of dead CTCs. The CTC count is more accurate, efficient with high sensitivity and specificity. It can also perform phenotypic analysis of CTC and single-cell sequencing. It can be used for screening, diagnosis, and guidance of targeted therapy for bladder cancer, assessing efficacy and judging prognosis which has a very broad clinical application prospect for advancing the accurate diagnosis and treatment of BC.
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Recently, studies showed that neutrophils extracellular traps (NETs) are the fiber network structures formed by the materials released by neutrophils under various appropriate stimulation. NETs have been indicated to trap and kill microorganisms, playing a critical role in immune responses. It was pointed out that NETs can not only be involved in inflammation and thrombosis, but also is intimately related to tumor metastasis. Therefore, the study of NETs in tumor metastasis is of great significance for tumor therapy and the progress of NETs in tumor metastasis and the relevant mechanisms is summarized. .
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Objective Circulating tumor cells (CTCs) have potential value in the clinical application of various tumors. This study was to investigate the role of CTCs and their chemokine receptor CCR9 in the invasion and metastasis of non-small cell lung cancer (NSCLC). Methods From May 2018 to June 2019, a total of 62 patients with NSCLC in the clinical oncology center of The People's Hospital of Guangxi Zhuang Autonomous Region were enrolled in this study. The CanpatrolTM CTC technique was used to detected the expressions of CTCs and CCR9 in CTCs in peripheral blood of patients. Furthermore, the relationships between expression levels of CTCs, CCR9 and clinical, pathological characteristics of NSCLC patients were analyzed. Results CTCs were detected in 56 of 62 (90.3%) NSCLC patients. CTCs counts were associated with TNM stage, lymph node metastasis and distant metastasis of NSCLC (P<0.05). In the analysis of clinical correlation between CTC subtypes and NSCLC, epithelial CTCs counts were related to TNM stage and distant metastasis of NSCLC (r=0.296 and r=0.273, P<0.05). Additionally, counts of mixed type CTCs were also correlative with NSCLC tumor metastasis (r =0.253, P =0.047). Finally, we found that the positive rate of CCR9 in mixed type CTCs was associated with distant metastasis of NSCLC (r=0.353, P=0.038). Conclusion CTCs counts and subtypes were correlated with TNM stage and metastasis of NSCLC. The expression level of CCR9 on CTC was expected to be a biomarker to evaluate the risk of tumor metastasis in NSCLC.
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Objective: To evaluate the practicability and feasibility of detection of circulating tumor cells (CTC) combined with exosome miR-21 in the diagnosis of ground glass opacity (GGO), and to provide the evidence for the diagnosis of GGO. Methods: Seventy patients were selected according to the diagnostic and exclusion criteria of GGO. All the patients underwent thoracoscopic segmentectomy. The patients diagnosed as lung cancer after operation were regarded as case group (n=24), and the patients diagnosed as benign lesion after operation were regarded as control group (n=46). Before operation, CTC was captured from the peripheral blood by negative enrichment of immunomagnetic beads. CTC was labeled with tumor-specific folate ligand-oligonucleotide conjugate. The exosomes of the same specimen were detected, purified and identified, and the expression levels of serum exosome miR-21 of the patients in two groups were detected. The diagnostic efficacies of CTC and exosome miR-21 in the GGO paitents were evaluated by ROC curves. Results: The positive rate of CTC in the patients in case group was higher than that in control group (P0. 05). The purified samples showed exosome characteristics. The expression level of serum exosome miR-21 in the patients in case group was higher than that in control group (P<0. 05). The area under ROC curve (AUC) of CTC was 0. 891, and the AUC of exosome miR-21 was 0.711, which showed good specificity. The sensitivity and specificity of the combined detection were 85.64% and 86.79%, respectively. Conclusion: The detection of CTC combined with exosome miR-21 can be used in the clinical diagnosis of early lung cancer with high sensitivity and specificity.
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Objective: To investigate the clinical significance and difference of peripheral blood circulating tumor cells (CTCs) detection in the prognosis of patients with gastric cancer and colorectal cancer. Methods: The CTCs in the peripheral blood of 32 patients with gastric cancer and 36 patients with colorectal cancer were detected by negative enrichment and imFISH technique, and the results were compared between the two groups. Results: There were 8 cases (25%) of CTCs 2 were detected, and only 8 cases survived. The two groups differed significantly in survival (P=0.001). 28 cases (78%) of the patients with colorectal cancer were detected CTCs 2 groups survived at the end of the follow-up. 6 patients survived at the end of the follow-up. There was a significant difference between CTCs 2 groups in colorectal cancer (P=0.044). The survival in gastric cancer and colorectal cancer was significantly different (P=0.000). The results of CTCs were not correlated with gender, age, lymph node metastasis, distant organ metastasis or pathological grade of patients with colorectal cancer and gastric cancer (all P>0.05). Conclusion: Negative enrichment and imFISH technique can be used to detect CTCs of the peripheral blood of patients with gastric cancer and colorectal cancer. The prognosis of patients with elevated CTCs is poor. Gastric cancer has a poorer prognosis than colorectal cancer.
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Collectively migrating tumor cells have been recently implicated in enhanced metastasis of epithelial malignancies. In oral squamous cell carcinoma (OSCC), v integrin is a crucial mediator of multicellular clustering and collective movement ; however, its contribution to metastatic spread remains to be addressed. According to the emerging therapeutic concept, dissociation of tumor clusters into single cells could significantly suppress metastasis-seeding ability of carcinomas. This study aimed to investigate the anti-OSCC potential of novel endostatin-derived polypeptide PEP06 as a cluster-dissociating therapeutic agent . Firstly, we found marked enrichment of v integrin in collectively invading multicellular clusters in human OSCCs. Our study revealed that metastatic progression of OSCC was associated with augmented immunostaining of v integrin in cancerous lesions. Following PEP06 treatment, cell clustering on fibronectin, migration, multicellular aggregation, anchorage-independent survival and colony formation of OSCC were significantly inhibited. Moreover, PEP06 suppressed v integrin/FAK/Src signaling in OSCC cells. PEP06-induced loss of active Src and E-cadherin from cell-cell contacts contributed to diminished collective migration of OSCC . Overall, these results suggest that PEP06 polypeptide 30 inhibiting v integrin/FAK/Src signaling and disrupting E-cadherin-based intercellular junctions possesses anti-metastatic potential in OSCC by acting as a cluster-dissociating therapeutic agent.
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There have been many recent exciting developments in biomimetic nanoparticles for biomedical applications. Inflammation, a protective response involving immune cells, blood vessels, and molecular mediators directed against harmful stimuli, is closely associated with many human diseases. As a result, biomimetic nanoparticles mimicking immune cells can help achieve molecular imaging and precise drug delivery to these inflammatory sites. This review is focused on inflammation-targeting biomimetic nanoparticles and will provide an in-depth look at the design of these nanoparticles to maximize their benefits for disease diagnosis and treatment.
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Taking inspiration from nature, the biomimetic concept has been integrated into drug delivery systems in cancer therapy. Disguised with cell membranes, the nanoparticles can acquire various functions of natural cells. The cell membrane-coating technology has pushed the limits of common nano-systems (fast elimination in circulation) to more effectively navigate within the body. Moreover, because of the various functional molecules on the surface, cell membrane-based nanoparticles (CMBNPs) are capable of interacting with the complex biological microenvironment of the tumor. Various sources of cell membranes have been explored to camouflage CMBNPs and different tumor-targeting strategies have been developed to enhance the anti-tumor drug delivery therapy. In this review article we highlight the most recent advances in CMBNP-based cancer targeting systems and address the challenges and opportunities in this field.