In recent years, the incidence of chest malignant tumors in China has increased year by year, which has seriously threatened the health problems of people. Among them, early screening and intervention of patients with chest malignancies is the key to cancer prevention. Early detection, early diagnosis, and early treatment as the "three early prevention" of clinical practice are conducive to improve the survival rate of tumor patients. As a non-invasive and real-time reflection of tumor status, liquid biopsy has gradually received attention in clinical diagnosis and treatment. Circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and exosomes as liquid biopsy "Three carriages" are not only widely used in the diagnosis, monitoring and prognostic evaluation of chest malignancies, but also face many unknown challenges. In this article, the application of liquid biopsy in chest malignancies in recent years is elaborated in detail, which provides a reference for the formulation of clinical tumor prevention and diagnosis and treatment strategies.
Humans ; Circulating Tumor DNA/genetics* ; Liquid Biopsy/methods* ; Neoplastic Cells, Circulating/pathology* ; China ; Biomarkers, Tumor

Circulating tumor DNA (ctDNA) is emerging as a novel biomarker for tumor evaluation, offering advantages such as high sensitivity and specificity, minimal invasiveness, and absence of radiation. Currently, various techniques including gene sequencing and PCR are employed for ctDNA detection. The utilization of ctDNA for monitoring minimal residual disease (MRD) enables comprehensive assessment of tumor status and early identification of tumor recurrence, achieving a remarkable detection sensitivity of 0.01%. Therefore, ctDNA holds promise as a biomarker for early diagnosis, treatment response monitoring, and prognosis prediction in solid tumors. This article reviews the commonly used methods for detecting ctDNA and their advantages in evaluating tumor MRD and guiding clinical diagnosis and treatment.
Humans ; Circulating Tumor DNA/genetics* ; Neoplasm, Residual/genetics* ; Biomarkers, Tumor/genetics* ; Neoplasm Recurrence, Local ; Prognosis

Diffuse large B-cell lymphoma (DLBCL) as an aggressive lymphoma, there has not a good molecular marker to assess the therapeutic efficacy and prognosis of the disease. As compared with the traditional deteation method, it was found that the circulating tumor DNA (ctDNA) can be used as a non-invasive specific biomarker which can dynamically provide the information about the lymphoma. ctDNA in DLBCL can be obtained by dideoxy chain termination method combined with PCR, so as to detect genetic markers, targeted sequences of gene which is related to lymphoma; the digital PCR (dPCR) for lymphoma somatic mutations and the detection of abnormal methylation; ctDNA is closely related to the diagncsis, therapeutic efficiency and prognosis of DLBCL, thus ctDNA can be used for the early detection, mid-term and prognostic monitoring in DLBCL, which makes ctDNA have a broad clinical applied prospect.
Biomarkers, Tumor ; Circulating Tumor DNA ; Humans ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Polymerase Chain Reaction ; Prognosis

Biomarkers ; Biomarkers, Tumor ; Circulating Tumor DNA/genetics* ; Female ; Genital Neoplasms, Female/diagnosis* ; Humans ; Prognosis

Lung cancer is one of the leading causes of all cancer-related deaths. Circulating tumor DNA (ctDNA) is released from apoptotic and necrotic tumor cells. Several sensitive techniques have been invented and adapted to quantify ctDNA genomic alterations. Applications of ctDNA in lung cancer include early diagnosis and detection, prognosis prediction, detecting mutations and structural alterations, minimal residual disease, tumor mutational burden, and tumor evolution tracking. Compared to surgical biopsy and radiographic imaging, the advantages of ctDNA are that it is a non-invasive procedure, allows real-time monitoring, and has relatively high sensitivity and specificity. Given the massive research on non-small cell lung cancer, attention should be paid to small cell lung cancer.
Biomarkers, Tumor/genetics* ; Carcinoma, Non-Small-Cell Lung ; Circulating Tumor DNA/genetics* ; Humans ; Lung Neoplasms/genetics* ; Mutation/genetics*

BACKGROUND: Circulating tumor DNA (ctDNA) is a promising biomarker for non-invasive epidermal growth factor receptor mutations (EGFRm) detection in lung cancer patients, but existing methods have limitations in sensitivity and availability. In this study, we used the ΔCt value (mutant cycle threshold [Ct] value-internal control Ct value) generated during the polymerase chain reaction (PCR) assay to convert super-amplification-refractory mutation system (superARMS) from a qualitative method to a semi-quantitative method named reformed-superARMS (R-superARMS), and evaluated its performance in detecting EGFRm in plasma ctDNA in patients with advanced lung adenocarcinoma. METHODS: A total of 41 pairs of tissues and plasma samples were obtained from lung adenocarcinoma patients who had known EGFRm in tumor tissue and were previously untreated. EGFRm in ctDNA was identified by using superARMS. Through making use of ΔCt value generated during the detection process of superARMS, we indirectly transform this qualitative detection method into a semi-quantitative PCR detection method, named R-superARMS. Both qualitative and quantitative analyses of the data were performed. Kaplan-Meier analysis was performed to estimate the progression-free survival (PFS) and overall survival (OS). Fisher exact test was used for categorical variables. RESULTS: The concordance rate of EGFRm in tumor tissues and matched plasma samples was 68.3% (28/41). At baseline, EGFRm-positive patients were divided into two groups according to the cut-off ΔCt value of EGFRm set at 8.11. A significant difference in the median OS (mOS) between the two groups was observed (EGFRm ΔCt ≤8.11 vs. >8.11: not reached vs. 11.0 months; log-rank P = 0.024). Patients were divided into mutation clearance (MC) group and mutation incomplete clearance (MIC) group according to whether the ΔCt value of EGFRm test turned negative after 1 month of treatment. We found that there was also a significant difference in mOS (not reached vs. 10.4 months; log-rank P = 0.021) between MC group and MIC group. Although there was no significant difference in PFS between the two groups, the two curves were separated and the PFS of MC group tended to be higher than the MIC group (not reached vs. 27.5 months; log-rank P = 0.088). Furthermore, EGFRm-positive patients were divided into two groups according to the cut-off of the changes in ΔCt value of EGFRm after 1 month of treatment, which was set at 4.89. A significant difference in the mOS between the two groups was observed (change value of ΔCt >4.89 vs. ≤4.89: not reached vs. 11.0 months; log-rank P = 0.014). CONCLUSIONS Detecting EGFRm in ctDNA using R-superARMS can identify patients who are more likely sensitive to targeted therapy, reflect the molecular load of patients, and predict the therapeutic efficacy and clinical outcomes of patients.
Adenocarcinoma of Lung/genetics* ; Circulating Tumor DNA/genetics* ; ErbB Receptors/genetics* ; Humans ; Lung Neoplasms/genetics* ; Mutation/genetics* ; Protein Kinase Inhibitors

Advanced breast cancer is a complicated disease with poor prognosis, which is difficult for salvage treatment. Although advanced breast cancer is difficult to cure at present, we can improve the life quality and prolong survival time of patients by applying optimized treatment. In recent years, with the rapid development of molecular biology and gene testing technology, studies on advanced breast cancer continue to deepen. Gene targeted therapy significantly extends the survival time of patients with advanced breast cancer. Gene testing is one of the important means for molecular typing, genetic diagnosis, therapeutic monitoring, drug resistance, and treatment choice of breast cancer, which is of great significance for the selection of targeted drugs and the management plan. In this consensus, the Expert Committee summarized ten hot issues of gene testing for advanced breast cancer and discussed the applicable population, clinical significance, and the application of molecular markers circulating tumor DNA (ctDNA), whole exome sequencing (WES) in different molecular types, and the standardization of next generation sequencing (NGS) technology applied in clinic. This consensus aimed to guide clinicians how to rationally apply the gene testing to know more comprehensive genetic testing information, and formulate more precise treatment strategies for patients with advanced breast cancer.
Biomarkers, Tumor/genetics* ; Breast Neoplasms/genetics* ; China ; Circulating Tumor DNA ; Consensus ; Female ; Genetic Testing ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation

With the concept of "Precision Medicine" in malignant tumors popularized, many substances carrying valuable clinical information have emerged in the process of exploring the occurrence and development of tumors from a microscopic perspective. Circulating tumor DNA (ctDNA) is one of them. In various clinical stages of cancer, ctDNA exhibits rich diagnostic values including demonstrating the efficacy of treatment, predicting prognosis, and monitoring disease recurrence. This article mainly describes the application and research progress of ctDNA in different stages of clinical diagnosis and treatment of non-small cell lung cancer .
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Biomarkers, Tumor/genetics* ; Carcinoma, Non-Small-Cell Lung/genetics* ; Circulating Tumor DNA/genetics* ; Humans ; Lung Neoplasms/genetics* ; Mutation ; Neoplasm Recurrence, Local

Non-small-cell lung cancer (NSCLC), the most common type of lung cancer accounting for 85% of the cases, is often diagnosed at advanced stages owing to the lack of efficient early diagnostic tools. 5-Hydroxymethylcytosine (5hmC) signatures in circulating cell-free DNA (cfDNA) that carries the cancer-specific epigenetic patterns may represent the valuable biomarkers for discriminating tumor and healthy individuals, and thus could be potentially useful for NSCLC diagnosis. Here, we employed a sensitive and reliable method to map genome-wide 5hmC in the cfDNA of Chinese NSCLC patients and detected a significant 5hmC gain in both the gene bodies and promoter regions in the blood samples from tumor patients compared with healthy controls. Specifically, we identified six potential biomarkers from 66 patients and 67 healthy controls (mean decrease accuracy >3.2, P < 3.68E-19) using machine-learning-based tumor classifiers with high accuracy. Thus, the unique signature of 5hmC in tumor patient's cfDNA identified in our study may provide valuable information in facilitating the development of new diagnostic and therapeutic modalities for NSCLC.
5-Methylcytosine ; analogs & derivatives ; blood ; Biomarkers, Tumor ; blood ; genetics ; Carcinoma, Non-Small-Cell Lung ; blood ; diagnosis ; genetics ; Case-Control Studies ; Circulating Tumor DNA ; blood ; DNA Methylation ; Epigenomics ; Female ; Humans ; Lung Neoplasms ; blood ; diagnosis ; genetics ; Male ; Middle Aged

OBJECTIVETo investigate the role of tissue factor (TF) in the invasion and hematogenous metastasis of human colorectal carcinoma cells.

METHODSThe eukaryotic expression vectors pcDNA3.1/Zeo bearing either sense or antisense TFcDNA were transfected into HT-29 and LoVo cells by the way of lipofactamine 2000. TF proteins in transfected cells were detected by Western Blot. Then the transfected and un-transfected tumor cells were implanted into nude mice (Balb/c Nu/Nu) to produce primary tumor, lung metastasis and liver metastasis respectively.

RESULTSHT-29 and LoVo cells with sense-TFcDNA transfection showed increased TF expression compared with the cells without transfection, but the cells with antisense-TFcDNA transfection got the contrary change. The primary tumor growth and invasive range, lung metastasis and live metastasis all increased in sense transfectants but reduced in antisense transfectants.

CONCLUSIONSTF can increase the invasion and hematogenous metastatic ability of human colorectal carcinoma cells.

Animals ; Cell Line, Tumor ; Colorectal Neoplasms ; genetics ; pathology ; DNA, Antisense ; genetics ; DNA, Complementary ; genetics ; Humans ; Liver Neoplasms ; secondary ; Lung Neoplasms ; secondary ; Male ; Mice ; Mice, Nude ; Neoplasm Invasiveness ; Neoplastic Cells, Circulating ; pathology ; Thromboplastin ; biosynthesis ; genetics ; physiology ; Transfection