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 summarize the molecular mechanisms and clinical treatment of gastric cancer with liver metastasis (GCLM), in order to provide new ideas for future treatment. MethodThe literatures about mechanism and treatment strategy of GCLM in recent years were searched and reviewed. ResultsMost patients with gastric cancer were in advanced stage or had developed distant metastases when they were first diagnosed, among which liver was the common site of metastasis. The complex molecular mechanisms of GCLM had not been fully clarified. Molecular mechanisms at different levels, including non-coding RNA, circulating tumor cells, exosomes, tumor microenvironment and signaling pathways, were relatively independent and interacted with each other, providing potential biomarkers and therapeutic targets for GCLM. At present, the best treatment method for patients with GCLM was mainly divided into local and systemic treatment. The local treatment included surgical treatment, radiofrequency ablation and proton beam therapy, while the systemic treatment included systemic chemotherapy, targeted therapy and immunotherapy, among which the targeted therapy and immunotherapy were the focus of recent research. ConclusionsThe mechanism of GCLM is the result of the interaction between tumor cells and the microenvironment at the site of metastasis. Understanding them is of great significance to guide clinical treatment and prognosis. At present, there is no unified treatment standard for GCLM. To achieve the ideal treatment effect, we should not only rely on single therapy, but also adopt multi-disciplinary and individual therapy according to the specific disease status of patients and the nature of tumors.
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 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 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.
Objective To investigate the relationships between circulating tumor cells (CTCs), circulating tumor endothelial cells (CTECs) and treatment methods in patients with nasopharyngeal carcinoma (NPC) at different stages of treatment. Methods The data of NPC patients at different treatment periods in West China Hospital of Sichuan University from March 2016 to November 2019 were retrospectively collected. The patients received CTCs test and part of those patients received CTECs test, by subtraction enrichment-immunostaining-fluorescence in situ hybridization. The relationships of CTCs and CTECs with radiotherapy and chemotherapy, and the correlations between CTCs and CTECs in NPC patients were analyzed. Results A total of 191 patients were included. Among them, there were 66 cases before initial treatment, 38 cases after induction chemotherapy, and 87 cases after concurrent chemoradiotherapy. A total of 127 patients received CTECs test, including 41 cases before initial treatment, 29 cases after induction chemotherapy, and 57 cases after concurrent chemoradiotherapy. The positive rates of CTCs were 89.4%, 81.6% and 69.0% respectively in the three stages of treatment, and the difference was statistically significant only between the pre-treatment group and the post-concurrent chemoradiotherapy group (P=0.003). The number of CTCs in the post-concurrent chemoradiotherapy group was lower than that in the pre-treatment group and the post-induction chemotherapy group (P<0.001, P=0.002). The number of triploid CTCs in the post-concurrent chemoradiotherapy group was significantly different from that in the pre-treatment group and the post-induction chemotherapy group (P=0.009, P=0.013). The number of tetraploid CTCs in the post-concurrent chemoradiotherapy group was significantly different from that in the post-induction chemotherapy group (P=0.007). The number of polyploidy (pentaploid or > 5 copies of chromosome 8) CTCs in the post-concurrent chemoradiotherapy group was significantly different from that in the pre-treatment group (P<0.001). The positive rates of CTECs were 70.7%, 82.8% and 64.9% respectively in the three stages of treatment, and the difference was not statistically significant (P>0.05). The number of CTECs in the post-concurrent chemoradiotherapy group was only lower than that in the post-induction chemotherapy group (P=0.009). There was no significant difference in the number of triploid or tetraploid CTECs among the three groups (P=0.265, P=0.088). The number of polyploid CTECs was statistically different only between the post-concurrent chemoradiotherapy group and the post-induction chemotherapy group (P=0.007). Spearman correlation analysis showed that there was a significant positive correlation between CTCs and CTECs (rs=0.437, P<0.001). Conclusions Concurrent chemoradiotherapy plays a decisive role in reducing the number of CTCs in the blood of NPC patients, while induction chemotherapy does not appear to directly cause changes in the number of CTCs. In NPC patients, different types of CTCs have different responses to different treatments. There is a significant positive correlation between CTECs level and CTCs level in NPC.
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 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.