Objective To summarize the new progress of circulating tumor cell markers and their clinical application. Methods The related literatures about the detection and clinical application of circulating tumor cell markers in recent years were reviewed. Resuts Epithelial markers, other markers such as human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and immuno-checkpoint genes have also become a useful means to detect the ability of malignant metastasis of circulating tumor cells (CTCs). Moreover, the epithelial-to-mesenchymal transition (EMT) and cancer stem cells (CSCs) have also received increasing attention as important CTCs markers owing to their roles in the biological progression of metastasis. Conclusions Through the detection of peripheral blood CTCs, to identify early cancer, monitoring the metastasis and recurrence of cancer and its treatment on all has the very good guiding significance. Signs of circulating tumor cells has great clinical application value in diagnosis and treatment of tumor and prognosis.
Objective To explore the efficacy of a novel detection technique of circulating tumor cells (CTCs) to identify benign and malignant lung nodules. Methods Nanomagnetic CTC detection based on polypeptide with epithelial cell adhesion molecule (EpCAM)-specific recognition was performed on enrolled patients with pulmonary nodules. There were 73 patients including 48 patients with malignant lesions as a malignant group and 25 patients with benign lesion as a benign group. There were 13 males and 35 females at age of 57.0±11.9 years in the malignant group and 11 males and 14 females at age of 53.1±13.2 years in the benign group. e calculated the differential diagnostic efficacy of CTC count, and conducted subgroup analysis according to the consolidation-tumor ratio, while compared with PET/CT on the efficacy. Results CTC count of the malignant group was significantly higher than that of the benign group (0.50/ml vs. 0.00/ml, P<0.05). Subgroup analysis according to consolidation tumor ratio (CTR) revealed that the difference was statistically significant in pure ground glass (pGGO) nodules 1.00/mlvs. 0.00/ml, P<0.05), but not in part-solid or pure solid nodules. For pGGO nodules, the area under the receiver operating characteristic (ROC) curve of CTC count was 0.833, which was significantly higher than that of maximum of standardized uptake value (SUVmax) (P<0.001). Its sensitivity and specificity was 80.0% and 83.3%, respectively. Conclusion The peptide-based nanomagnetic CTC detection system can differentiate malignant tumor and benign lesions in pulmonary nodules presented as pGGO. It is of great clinical potential as a noninvasive, nonradiating method to identify malignancies in pulmonary nodules.
ObjectiveTo detect level of circulating tumor cells (CTCs) in peripheral venous blood of fasting patients with gastric cancer (GC) and to analyze relationships between CTCs and clinicopathologic features and prognosis of patients with GC.MethodsOne hundred patients with GC were selected (GC group), who underwent the surgery and confirmed by the histopathology in the 940 Hospital of Joint Service of PLA, from August 2015 to December 2016. Thirty-eight patients with gastric benign lesions who were treated in this hospital at the same time were selected as the control group. The 7 mL peripheral venous blood of the elbow in the morning was taken from the fasting patients and the CTCs were detected by the immunomagnetic microparticle negative enrichment combined with immunofluorescence in situ hybridization within 24 h. The positive rate of CTCs was calculated and its relationships with the clinicopathologic features (tumor location, tumor invasion depth, degree of differentiation, TNM stage, lymph node metastasis, and vascular tumor thrombus) and the progression-free survival of the patients with GC were analyzed.ResultsThe positive rate of peripheral venous blood CTCs in the GC group was 89.0% (89/100), which was higher than that in the control group (10.5%, 4/38), and the difference was statistically significant (P<0.001). The levels of CTCs in the patients with GC were significantly correlated with the tumor invasion depth (P=0.017), lymph node metastasis (P=0.038), and TNM stage (P=0.016), which were not associated with the age, gender, tumor location, degree of differentiation, and vascular tumor thrombus (P>0.050). The predictive value of CTCs for the diagnosis of GC was significantly superior to that of the tumor markers CEA, CA19-9, or CA125. The progression-free survival of patients with low CTCs expression was significantly longer than that in the patients with high CTCs expression (χ2=5.172, P=0.023).ConclusionsDetecting CTCs of patients with GC by immunomagnetic particle negative enrichment combined with immunofluorescence in situ hybridization has a high sensitivity. And it can improve early diagnosis of patients with GC. Preoperative CTCs detection has a certain value in guiding staging of GC and predicting prognosis of patients with GC.
ObjectiveCD44 and CD54 are two specific biomarkers of gastric cancer stem cells and were used as targets in this study. The number of CD45–CD44+CD54+ cell subsets in peripheral blood of gastric cancer patients was detected by flow cytometry. Further, we combined these results with the clinicopathological characteristics of gastric cancer patients to analyze the significance of CD45–CD44+CD54+ cell subsets.MethodsFrom December 2016 to September 2017, 38 patients with gastric cancer in gastrointestinal surgery of West China Hospital of Sichuan University were included as the study object. The content of CD45–CD44+CD54+ cell subsets in their peripheral blood was detected by flow cytometry and its clinical significance was analyzed.ResultsThe median number of CD45–CD44+CD54+ cells were 541.9/mL (71.7–8 057.0/mL) in 38 patients and 555.9/mL (71.7–8 057.0/mL) in the group of patients with R0 resection. Patients without lymph node metastasis were found to have more CD45–CD44+CD54+ cells than patients with lymph node metastasis [941.4/mL (183.5–8 057.0)/mL vs 379.3/mL (71.7–2 269.7/mL, P=0.002], and more CD45–CD44+CD54+ cells in patients with TNM stage Ⅰ–Ⅱ than in TNM stage Ⅲ–Ⅳ [858.6/mL (183.5–8 057.0/mL) vs 364.6/mL (71.7–2 269.7/mL, P=0.015]. The patients with T3–4 stages (P= 0.025), N+ stage (P=0.009) and TNM Ⅲ–Ⅳ stage (P=0.012) had low ratios of the subgroup with high number of CD45–CD44+CD54+ cells, respectively. We made a more accurate judgment of N stage and TNM stage when we combined tumor size and the number of CD45–CD44+CD54+ cells together. However, there was no significant correlation between the number of CD45–CD44+CD54+ cells and other clinicopathological features and prognosis.ConclusionsThe number of CD45–CD44+CD54+ cell subsets is correlated with tumor progression, which might be used to predict TNM stage and N stage. However, the number of patients included in this study is too small, and the clinical significance of CD45–CD44+CD54+ subsets in gastric cancer patients needs to be further demonstrated by expanding the sample size.
ObjectiveTo 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.MethodsA 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.ResultsTotally 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.ConclusionFR+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.
Objective To investigate the clinical significance of circulating tumor cells (CTC) in gastric cancer patients treated with surgery and to assess its prognostic value for gastric cancer patients. Methods A case-control study was conducted to retrospectively collect the clinicopathological data of gastric cancer patients who underwent radical gastric cancer surgery at the Department of General Surgery, First Medical Center of the Chinese People’s Liberation Army General Hospital between April 2015 and July 2017, and who underwent postoperative CTC examination. The optimal cut-off value was determined by drawing a receiver operating characteristic (ROC) curve based on CTC levels and patient survival, and patients were divided into CTC-positive and negative groups based on this cut-off value to investigate the differences in clinicopathological characteristics between the two groups. Patients with gastric cancer were followed up and survival was recorded until September 30, 2020. The Kaplan-Meier method was used to calculate the 3-year overall survival rate and plot survival curves, and Cox regression models were used to conduct univariate and multifactorial analyses of patient prognostic factors to explore the factors affecting the survival of patients after gastric cancer surgery. Results A total of 242 patients with gastric cancer were included in this study. The results of ROC curve analysis showed that the most statistically significant CTC cut-off value for patient survival difference was 1, which meant that patients were considered positive when CTC was detected in their blood. Forty-nine cases (20.2%) in the CTC positive group had a positive cell count of 1 to 32 cells/7.5 mL, with a median of 2 cells/ 7.5 mL, and 193 cases (79.8%) in the negative group. Comparison of baseline data between the two groups showed that there were no statistically significant differences in patients’ age, gender, tumor site, surgical method, type of resection, anastomosis, tumor diameter, lymph node metastasis and nerve invasion (all P>0.05), and statistically significant differences in body mass index, choroidal carcinoma embolus, degree of tumor differentiation, tumor pathological type, and tumor TNM stage (all P<0.05). The median follow-up time after surgery for 242 gastric cancer patients was 42 (3–67) months, and the 3-year survival rates were 49.0% and 72.5% in the CTC-positive and -negative groups, respectively, with statistically significant difference (χ2=17.129, P<0.001). The results of univariate analysis showed that age, tumor site, type of resection, anastomosis, tumor diameter, lymph node metastasis, choroidal carcinoma embolism, nerve invasion, degree of tumor differentiation, tumor TNM stage, and whether CTC was positive or not were the important factors affecting the overall survival rate of gastric cancer patients (all P<0.05). The results of multivariate analysis showed that age >60 years old [HR=3.009, 95%CI(1.807, 5.010), P<0.001], tumor TNM Ⅲ–Ⅳ stage [HR=3.082, 95%CI (1.504, 6.317), P=0.002] and positive CTC [HR=2.488, 95%CI (1.475, 4.197), P=0.001] were independent risk factors affecting the survival of gastric cancer patients. Conclusion CTC is correlated with the prognosis of gastric cancer patients and can be used as a potential indicator to determine the prognosis of gastric cancer patients.
The important detection indicators of liquid biopsy in cancer patients include circulating tumor cells and circulating tumor DNA. The former refers to the cells that fall off from the primary tumor and metastatic sites and enter the blood circulation through blood vessels or lymphatic vessels, while the latter refers to the cell-free DNA released into the blood vessels by apoptotic or necrotic tumor cells. For breast cancer patients receiving neoadjuvant therapy, dynamic monitoring of circulating tumor cells and circulating tumor DNA can help early identify the responsiveness of tumor patients to different treatments and guide subsequent treatments to improve prognosis. This article reviews the research progress and clinical significance of detecting circulating tumor cells and circulating tumor DNA in breast cancer patients receiving neoadjuvant therapy, aiming to provide a reference for the more rational application of circulating tumor cells and circulating tumor DNA in neoadjuvant therapy of breast cancer.
Objective To evaluate the clinical radiological features combined with circulating tumor cells (CTCs) in the diagnosis of invasiveness evaluation of subsolid nodules in lung cancers. Methods Clinical data of 296 patients from the First Hospital of Lanzhou University between February 2019 and February 2021 were retrospectively included. There were 130 males and 166 females with a median age of 62.00 years. Patients were randomly divided into a training set and an internal validation set with a ratio of 3 : 1 by random number table method. The patients were divided into two groups: a preinvasive lesion group (atypical adenomatoid hyperplasia and adenocarcinoma in situ) and an invasive lesion group (microinvasive adenocarcinoma and invasive adenocarcinoma). Independent risk factors were selected by regression analysis of training set and a Nomogram prediction model was constructed. The accuracy and consistency of the model were verified by the receiver operating characteristic curve and calibration curve respectively. Subgroup analysis was conducted on nodules with different diameters to further verify the performance of the model. Specific performance metrics, including sensitivity, specificity, positive predictive value, negative predictive value and accuracy at the threshold were calculated. Results Independent risk factors selected by regression analysis for subsolid nodules were age, CTCs level, nodular nature, lobulation and spiculation. The Nomogram prediction mode provided an area under the curve (AUC) of 0.914 (0.872, 0.956), outperforming clinical radiological features model AUC [0.856 (0.794, 0.917), P=0.003] and CTCs AUC [0.750 (0.675, 0.825), P=0.001] in training set. C-index was 0.914, 0.894 and corrected C-index was 0.902, 0.843 in training set and internal validation set, respectively. The AUC of the prediction model in training set was 0.902 (0.848, 0.955), 0.913 (0.860, 0.966) and 0.873 (0.730, 1.000) for nodule diameter of 5-20 mm, 10-20 mm and 21-30 mm, respectively. Conclusion The prediction model in this study has better diagnostic value, and is more effective in clinical diagnosis of diseases.
Lung cancer is a malignant tumor with the highest mortality worldwide, and its early diagnosis and evaluation have a crucial impact on the comprehensive treatment of patients. Early preoperative diagnosis of lung cancer depends on a variety of imaging and tumor marker indicators, but it cannot be accurately assessed due to its high false positive rate. Liquid biopsy biomarkers can detect circulating tumor cells and DNA in peripheral blood by non-invasive methods and are gradually becoming a powerful diagnostic tool in the field of precision medicine for tumors. This article reviews the research progress of liquid biopsy biomarkers and their combination with clinical imaging features in the early diagnosis of lung cancer.
ObjectiveTo understand the latest progress of enrichment technology of circulating tumor cells (CTCs), and summarize the principle, advantages and disadvantages of various enrichment technologies and their applications in primary liver cancer (PLC). MethodThe literature relevant to the enrichment methods of CTCs in the PLC was reviewed and summarized. ResultsThe clinical significances of CTCs in the early diagnosis and staging, hierarchical diagnosis and treatment, and efficacy monitoring of patients with PLC had been recognized. There were many separation and enrichment technologies for CTC, which were mainly based on the differences of physical and biochemical characteristics, as well as the combination of enrichment methods with various principles. Each enrichment method had corresponding advantages and disadvantages, and few enrichment methods for CTC was applied to PLC. ConclusionsAlthough many problems need to be solved in enrichment method of CTCs at present, it is believed that the existing problems will be solved one by one with continuous improvement of technology. And CTC detection is expected to apply in clinical, so as to provide more efficient diagnosis and treatment methods for patients with PLC.