Objective To assess the efficacy of a kind of new material lipid magnetic particle for isolation and detection of lung cancer circulating tumor cells (CTCs). Methods Immune lipid magnetic particles were prepared with reverse evaporation method and they were assembled into kits with EpCAM and EGFR antibody respectively. Their efficacy were evaluated by detecting A549 cells in group A (A549 cells mixed in phosphated buffer solution) and group B (A549 cells mixed in blood from healthy volunteers). Lung cancer CTCs of hospitalized patients were also detected with both immune magnetic particals. Then the detecting efficacy was compared between EpCAM immune lipid magnetic particles and the conventional CellsearchTM system. Results The immune lipid magnetic particles had high capture efficiency for CTCs isolation and identification. The median of EpCAM immune lipid magnetic particles method in detecting A549 cells in group A was 92%, and EGFR was 90%. The median of EpCAM immune lipid magnetic particles method in detecting A549 cells in group B was 85%, and EGFR was 81%. In 13 patients with lung cancer, CTCs can be detected with both immune lipid magnetic particles methods and both medians were 5; In negative control, the medians of both methods were 0 (P＜0.05). EpCAM immune lipid magnetic particles method can detect more CTCs than conventional CellsearchTM system in 3 lung cancer patients. Conclusions Immune lipid magnetic particles have good efficacy for lung cancer CTCs detection and has promising clinical application value. The EpCAM immune lipid magnetic particles have equal efficiency in detecting lung cancer CTCs with EGFR. There is a trend that EpCAM immune lipid magnetic particles is superior to the conventional CellsearchTM system.
Objective To summary the advance of circulating tumor cells in breast cancer. Methods Through reviewing the related studies, a series of clinical studies on advance of circulating tumor cells in breast cancer were reviewed. Results For early breast cancer patients, the detection of circulating tumor cells could find patients at high risk of recurrence and metastasis. For metastatic breast cancer patients, it could assess the efficacy of adjuvant chemotherapy and predict the prognosis. To explore the molecular characteristics of circulating tumor cells could help to understand tumor transfer mechanism and seek new therapeutic targets. Conclusion Circulating tumor cells play an important role in the treatment of breast cancer, but many multi-center prospective studies are needed to ensure whether circulating tumor cells can be used in clinical practice.
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.
Objective To explore the diagnostic value of circulating tumor cells (CTC) measured by magnetic nanoparticle method in lung cancer. Methods (1) We measured binding capability of A549 or NCI-H1965 cell lines with recognition peptide and capture efficiency by adding tumor cells into the whole blood of healthy human. (2) We measured CTC of 34 patients suspected with lung cancer, and the counting results of CTC were compared with the following pathological results. Results (1) The binding capability was 80.0%±6.0% for A549 and 70.1%±4.8% for H1957, while the capture efficiency was 57.3%±7.0% for A549 and 37.3%±6.1% for H1975. (2) CTCs were identified in 71.9% of patients with lung cancer. The specificity was 83.3%, and area under receiver operating characteristic (ROC) curve was 0.792 (P=0.003). Conclusion CTC measured by magnetic nanoparticle method has promising application in the diagnosis of lung cancer.
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.
Tumor cells have unique energy metabolism phenomena, namely high glucose absorption, aerobic glycolysis and high lactic acid production, which are characterized by down-regulation of related proteins involved in oxidative metabolism in tumor cells, and up-regulation of glucose transporters and monocarboxylate transporters. Studies have shown that drugs that target tumor cell glucose metabolism have the ability to selectively kill tumor cells, bringing new hope for tumor treatment. Tumor stem cells are considered to be the root cause of tumor recurrence, metastasis and poor prognosis, and their energy metabolism characteristics have not yet been agreed. Studies have shown that reversing the energy metabolism of tumor stem cells can increase their chemosensitivity. This article reviews recent studies on tumor and tumor stem cell glucose metabolism and the opportunities and challenges of tumor treatment through targeting glucose metabolism, which might provide new ideas and opportunities for clinical tumor therapy.
Lung cancer is the most frequent cancer and the leading cause of cancer death all around the world. Anti-programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) therapies have significantly improved the outcomes of non-small cell lung cancer (NSCLC) patients in recent years. However, the objective response rate in non-screened patients is only about 20%. It is very important to screen out the potential patients suitable for immunotherapy. Immunohistochemical staining of tumor tissue biopsies with PD-L1 antibodies can predict the therapeutic response to immunotherapy to some extent, but it still has some limitations. Recently some clinical studies have shown that PD-L1 expression in circulating tumor cells (CTC-PD-L1) is a potential independent biomarker and may provide important information for immunotherapy in NSCLC. This article will review technology for CTC-PD-L1 detection and the predictive value of CTC-PD-L1 for immunotherapy in NSCLC and review the latest clinical research progress.
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.