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 The prognostic impact of obstructive lung disease on survival of never smokers with resected non-small-cell lung cancer: a comparison with smokers

2019 ◽  
Vol 28 (5) ◽  
pp. 735-743
Author(s):  
Takaki Akamine ◽  
Tetsuzo Tagawa ◽  
Mototsugu Shimokawa ◽  
Taichi Matsubara ◽  
Yuka Kozuma ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Disease ◽  
Obstructive Lung Disease ◽  
Small Cell ◽  
Recurrence Free Survival ◽  
Small Cell Lung ◽  
Cancer Specific Survival ◽  
Free Survival ◽  
Never Smokers ◽  
Nsclc Patients

Abstract OBJECTIVES The proportion of never smokers among non-small-cell lung cancer (NSCLC) patients has steadily increased in recent decades, suggesting an urgent need to identify the major underlying causes of disease in this cohort. Chronic obstructive pulmonary disease is a risk factor for lung cancer in both smokers and never smokers. The aim of this study was to investigate the association between obstructive lung disease and survival in never smokers and smokers with NSCLC after complete resection. METHODS We retrospectively reviewed data from 548 NSCLC patients treated at our institution. The effects of obstructive lung disease on recurrence-free survival and cancer-specific survival following the resection of NSCLC were determined by univariable and multivariable Cox regression analyses. RESULTS Among the 548 patients analysed, 244 patients (44.5%) were never smokers and 304 patients (55.4%) were current or former smokers. In the never-smoker group, 48 patients (19.7%) had obstructive lung disease, 185 patients (75.8%) were women and 226 patients (92.6%) had adenocarcinoma. Obstructive lung disease was significantly associated with shorter recurrence-free survival (P = 0.006) and cancer-specific survival (P = 0.022) in the never smokers, but not the smokers, on both univariable and multivariable analyses. The associations between obstructive lung disease and prognosis in never smokers remained significant after propensity score matching. CONCLUSIONS Obstructive lung disease is an independent prognostic factor for recurrence-free survival and cancer-specific survival in never smokers, but not in smokers, with NSCLC. Based on this finding, further examination is warranted to advance our understanding of the mechanisms associated with NSCLC in never smokers.

Plasma cell-free DNA level and its integrity as biomarkers to distinguish non-small cell lung cancer from tuberculosis

2018 ◽  
Vol 477 ◽  
pp. 160-165 ◽  
Author(s):  
Shaoyi Leng ◽  
Jianjun Zheng ◽  
Yinhua Jin ◽  
Hongbin Zhang ◽  
Ya Zhu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Plasma Cell ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Free Dna ◽  
Free Dna

Targeted sequencing of plasma cell-free DNA to predict response to PD1 inhibitors in advanced non-small cell lung cancer

Lung Cancer ◽  
2019 ◽  
Vol 137 ◽  
pp. 1-6 ◽  
Author(s):  
Nicolas Guibert ◽  
Greg Jones ◽  
John F. Beeler ◽  
Vincent Plagnol ◽  
Clive Morris ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Plasma Cell ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Targeted Sequencing ◽  
Small Cell Lung ◽  
Cell Free Dna ◽  
Free Dna

scholarly journals Number of metastatic lymph nodes and zones as prognostic factors in non-small-cell lung cancer

2020 ◽  
Vol 31 (3) ◽  
pp. 305-314
Author(s):  
Tomohiro Maniwa ◽  
Akiisa Ohmura ◽  
Takashi Hiroshima ◽  
Akihiro Ike ◽  
Toru Kimura ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Small Cell ◽  
Recurrence Free Survival ◽  
Small Cell Lung ◽  
Free Survival ◽  
Nsclc Patients ◽  
Relationship Of ◽  
The Relationship

Abstract OBJECTIVES Characterizing pathological nodes (pNs) by location alone is sometimes inadequate as patients with pN1 or pN2 non-small-cell lung cancer (NSCLC) show prognostic heterogeneity. We aimed to assess the relationship of the number of metastatic lymph nodes (LNs) and zones with prognosis in NSCLC patients. METHODS We analysed 1393 patients who underwent lobectomy with mediastinal LN dissection for NSCLC at the Osaka International Cancer Institute between January 2006 and December 2015. Patients were classified into 3 groups according to the number of LNs: n1–3, n4–6 and n7–. We investigated the relationship of prognosis with the number of metastatic LNs and metastatic zones. RESULTS In the multivariable analyses, the number of metastatic LNs and zones were not independent factors for overall survival or recurrence-free survival in patients with pN1 disease after adjustment for age, sex, tumour histology and tumour diameter. However, n4–6 (ref. n1–3) was an independent prognostic factor for overall survival [hazard ratio (HR) 4.148, P &lt; 0.001] in those with pN2 disease. There were no significant differences in overall survival and recurrence-free survival between pN1 (HR 0.674, P = 0.175) and pN2n1–3 disease (HR 1.056, P = 0.808). Moreover, patients with pN2 disease with a higher number of metastatic zones had a poor prognosis for recurrence-free survival [3 zones (ref. 1): HR 1.774, P = 0.051, and 4 zones (ref. 1): HR 2.173, P &lt; 0.047]. CONCLUSIONS The number of metastatic LNs and metastatic zones were useful prognostic factors in NSCLC patients. The findings could help in establishing a new pN classification.

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 Negative Effect of Reduced NME1 Expression on Recurrence-Free Survival in Early Stage Non-Small Cell Lung Cancer

2020 ◽  
Vol 9 (10) ◽  
pp. 3067
Author(s):  
Dohun Kim ◽  
Yujin Kim ◽  
Bo Bin Lee ◽  
Dongho Kim ◽  
Ok-Jun Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Chemotherapy ◽  
Early Stage ◽  
Small Cell ◽  
Recurrence Free Survival ◽  
Small Cell Lung ◽  
Free Survival ◽  
Early Stage Nsclc ◽  
Negative Effect ◽  
Nsclc Patients

This study aimed to understand whether the effect of non-metastatic cells 1 (NME1) on recurrence-free survival (RFS) in early stage non-small cell lung cancer (NSCLC) can be modified by β-catenin overexpression and cisplatin-based adjuvant chemotherapy. Expression levels of NME1 and β-catenin were analyzed using immunohistochemistry in formalin-fixed paraffin-embedded tissues from 425 early stage NSCLC patients. Reduced NME1 expression was found in 39% of samples. The median duration of follow-up was 56 months, and recurrence was found in 186 (44%) of 425 patients. The negative effect of reduced NME1 expression on RFS was worsened by cisplatin-based adjuvant chemotherapy (adjusted hazard ratio = 3.26, 95% CI = 1.16–9.17, p = 0.03). β-catenin overexpression exacerbated the effect of reduced NME1 expression on RFS and the negative effect was greater when receiving cisplatin-based adjuvant chemotherapy: among patients treated with cisplatin-based adjuvant chemotherapy, hazard ratios of patients with reduced NME1 expression increased from 5.59 (95% confidence interval (CI) = 0.62–50.91, p = 0.13) to 15.52 (95% CI = 2.94–82.38, p = 0.001) by β-catenin overexpression, after adjusting for confounding factors. In conclusion, the present study suggests that cisplatin-based adjuvant chemotherapy needs to be carefully applied to early stage NSCLC patients with overexpressed β-catenin in combination with reduced NME1 expression.

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