scholarly journals Use of cell free DNA as a prognostic biomarker in non-small cell lung cancer patients with bone metastasis

2019 ◽  
Vol 34 (4) ◽  
pp. 381-388 ◽  
Author(s):  
Yongjian Ye ◽  
Zhihang Luo ◽  
Dejun Shi
Keyword(s):  
Lung Cancer ◽  
Survival Analysis ◽  
Bone Metastasis ◽  
Peripheral Blood ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Free Dna ◽  
Free Dna ◽  
Metastatic Sites ◽  
Nsclc Patients

Background: Non-small cell lung cancer (NSCLC) is difficult to treat when metastasis has occurred. This study explores the use of cell-free DNA in the clinical management of NSCLC patients who have Kirsten rat sarcoma viral oncogene homolog (KRAS)-positive mutations and as a marker for prognosis. Methods: Peripheral blood collected from advanced NSCLC patients was examined with digital droplet polymerase chain reaction and ultraviolet spectrometry. KRAS mutations were analyzed and quantitated. The specificity and sensitivity of the proposed assay was computed by associating the results with tumor tissue specimens. Comparison against different sub-groups of patients with different metastatic sites and healthy volunteers were made. Patients were subsequently followed up and survival analysis was conducted. Results: Among the 186 patients recruited, 150 had concordant KRAS mutational profiles using cell-free DNA with tumor tissues. The assay sensitivity and specificity were 80.6% and 100%, respectively. For the 150 patients with concordant results, the range of cell-free DNA quantities in peripheral blood was 5.3 to 115 ng. Among the patient groups with different metastatic sites, we observed that patients with bone metastasis had higher concentrations of cell-free DNA. Survival analysis showed that these patients had worse survival outcome. Patients with higher KRAS counts in peripheral blood also had worse outcome. Conclusion: The use of cell-free DNA presents opportunities for risk stratification of patients and possibly aids in the clinical management of the disease. In the current study for NSCLC, patients with bone metastases showed higher cell-free DNA concentrations. Quantitating the concentrations of cell-free DNA presents a noninvasive biomarker capable of prognostic utility.

scholarly journals Aberrant Methylation of SLIT2 Gene in Plasma Cell-Free DNA of Non-Small Cell Lung Cancer Patients

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 296
Author(s):  
Yujin Kim ◽  
Bo Bin Lee ◽  
Dongho Kim ◽  
Sang-Won Um ◽  
Joungho Han ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Plasma Cell ◽  
Small Cell ◽  
Aberrant Methylation ◽  
Recurrence Free Survival ◽  
Small Cell Lung ◽  
Cell Free Dna ◽  
Free Survival ◽  
Free Dna ◽  
Nsclc Patients

This study aimed to understand aberrant methylation of SLITs genes as a biomarker for the early detection and prognosis prediction of non-small cell lung cancer (NSCLC). Methylation levels of SLITs were determined using the Infinium HumanMethylation450 BeadChip or pyrosequencing. Five CpGs at the CpG island of SLIT1, SLIT2 or SLIT3 genes were significantly (Bonferroni corrected p < 0.05) hypermethylated in tumor tissues obtained from 42 NSCLC patients than in matched normal tissues. Methylation levels of these CpGs did not differ significantly between bronchial washings obtained from 76 NSCLC patients and 60 cancer-free patients. However, methylation levels of SLIT2 gene were significantly higher in plasma cell-free DNA of 72 NSCLC patients than in that of 61 cancer-free patients (p = 0.001, Wilcoxon rank sum test). Prediction of NSCLC using SLIT2 methylation was achieved with a sensitivity of 73.7% and a specificity of 61.9% in a plasma test dataset (N = 40). A Cox proportional hazards model showed that SLIT2 hypermethylation in plasma cell-free DNA was significantly associated with poor recurrence-free survival (hazards ratio = 2.19, 95% confidence interval = 1.21–4.36, p = 0.01). The present study suggests that aberrant methylation of SLIT2 in plasma cell-free DNA is a valuable biomarker for the early detection of NSCLC and prediction of recurrence-free survival. However, further research is needed with larger sample size to confirm results.

scholarly journals Evaluation of sensitivity and specificity of CanPatrol™ technology for detection of circulating tumor cells in patients with non-small cell lung cancer

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jingyao Li ◽  
Yi Liao ◽  
Yaling Ran ◽  
Guiyu Wang ◽  
Wei Wu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Survival Analysis ◽  
Small Cell Lung Cancer ◽  
Tumor Cells ◽  
Sensitivity And Specificity ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Kaplan Meier ◽  
Nsclc Patients

Abstract Background The early diagnosis of non-small cell lung cancer is of great significance to the prognosis of patients. However, traditional histopathology and imaging screening have certain limitations. Therefore, new diagnostical methods are urgently needed for the current clinical diagnosis. In this study we evaluated the sensitivity and specificity of CanPatrol™ technology for the detection of circulating tumor cells in patients with non-small cell lung cancer (NSCLC). Methods CTCs in the peripheral blood of 98 patients with NSCLC and 38 patients with benign pulmonary diseases were collected by the latest typing of CanPatrol™ detection technology. A 3-year follow-up was performed to observe their recurrence and metastasis. Kruskal-Wallis test was used to compare multiple groups of data, Mann-Whitney U test was used to compare data between the two groups, and ROC curve analysis was used to obtain the critical value. The COX risk regression and Kaplan-Meier survival analysis were performed in the 63 NSCLC patients who were effectively followed up. Results The epithelial, epithelial-mesenchymal, and total CTCs were significantly higher in NSCLC patients than that in patients with benign lung disease (P <  0.001). The mesenchymal CTCs of NSCLC patients was slightly higher than that of benign lung diseases (P = 0.013). The AUC of the ROC curve of the total CTCs was 0.837 (95% CI: 0.76-0.914), and the cut-off value corresponding to the most approximate index was 0.5 CTCs/5 ml, at which point the sensitivity was 81.6% and the specificity was 86.8%. COX regression analysis revealed that the clinical stage was correlated with patient survival (P = 0.006), while gender, age, and smoking were not (P > 0.05). After excluding the confounders of staging, surgery, and chemotherapy, Kaplan-Meier survival analysis showed that patients in stage IIIA with CTCs ≥0.5 had significantly lower DFS than those with CTCs < 0.5 (P = 0.022). Conclusions CTC positive can well predict the recurrence of NSCLC patients. CanPatrol™ technology has good sensitivity and specificity in detecting CTCs in peripheral blood of NSCLC patients and has a certain value for clinical prognosis evaluation.

scholarly journals Clinical Utility of Comprehensive Cell-free DNA Analysis to Identify Genomic Biomarkers in Patients with Newly Diagnosed Metastatic Non–small Cell Lung Cancer

2019 ◽  
Vol 25 (15) ◽  
pp. 4691-4700 ◽  
Author(s):  
Natasha B. Leighl ◽  
Ray D. Page ◽  
Victoria M. Raymond ◽  
Davey B. Daniel ◽  
Stephen G. Divers ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Clinical Utility ◽  
Dna Analysis ◽  
Small Cell ◽  
Newly Diagnosed ◽  
Small Cell Lung ◽  
Cell Free Dna ◽  
Free Dna

scholarly journals Interleukin-35 Suppresses the Antitumor Activity of T Cells in Patients with Non-Small Cell Lung Cancer

2018 ◽  
Vol 47 (6) ◽  
pp. 2407-2419 ◽  
Author(s):  
Hong-Min Wang ◽  
Xiao-Hong Zhang ◽  
Ming-Ming Feng ◽  
Yan-Jun Qiao ◽  
Li-Qun Ye ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

Background/Aims: Interleukin (IL)-35 has immunosuppressive functions in autoimmune diseases, infectious diseases, and certain cancers. However, few studies have focused on its immunoregulatory activity in non-small cell lung cancer (NSCLC). Thus, we investigated the role of IL-35 in the pathogenesis of this disease. Methods: A total of 66 NSCLC patients and 21 healthy individuals were enrolled. IL-35 expression in peripheral blood and bronchoalveolar lavage fluid (BALF) was measured. The modulatory functions of IL-35 on purified CD4+ and CD8+ T cells from NSCLC patients were investigated in direct and indirect coculture systems with NSCLC cell lines. Results: IL-35 expression was significantly increased in BALF from the tumor site, but not in the peripheral blood of NSCLC patients. IL-35 did not affect the bioactivity including proliferation, cytokine production, cell cycle, and cellular invasion of NSCLC cells. It suppressed responses from type 1 T helper (Th1) and Th17 cells but elevated the regulatory T cell response in cultured CD4+ T cells from NSCLC patients, and reduced cytokine-mediated CD4+ T cells cytotoxicity to NSCLC cells. Moreover, IL-35 also inhibited cytotoxic gene expression in CD8+ T cells from NSCLC, reducing their cytolytic and noncytolytic functions. Conclusion: The results of this study suggest that IL-35 contributes to the dysfunction/exhaustion of T cells and limited antitumor immune responses in NSCLC.

Abstract LB-A05: Profiling cell free DNA in breast cancer and non-small cell lung cancer using broad NGS assessment

2015 ◽  
Author(s):  
Nadia Solovieff ◽  
Matt Hims ◽  
Rebecca Leary ◽  
Derek Chiang ◽  
Caroline Germa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Free Dna ◽  
Free Dna
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