scholarly journals Methylation of DROSHA and DICER as a Biomarker for the Detection of Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6139
Author(s):  
Michał Szczyrek ◽  
Anna Grenda ◽  
Barbara Kuźnar-Kamińska ◽  
Paweł Krawczyk ◽  
Marek Sawicki ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Early Stage ◽  
Small Sample Size ◽  
Methylation Status ◽  
Small Sample ◽  
Relative Level ◽  
Lung Cancer Patients ◽  
Promoter Sequences ◽  
Early Stage Nsclc

Background: Lung cancer is the leading cause of cancer-related deaths. Early diagnosis may improve the prognosis. Methods: Using quantitative methylation-specific real-time PCR (qMSP-PCR), we assessed the methylation status of two genes (in two subsequent regions according to locations in their promoter sequences) related to carcinogenesis, DICER and DROSHA, in 101 plasma samples (obtained prior to the treatment) of lung cancer patients and 45 healthy volunteers. Results: The relative level of methylation of DROSHA was significantly lower (p = 0.012 for first and p < 0.00001 for the second region) and DICER significantly higher (p = 0.029 for the first region) in cancer patients. The relative level of methylation of DROSHA was significantly (p = 0.037) higher in patients with early-stage NSCLC (IA-IIIA) and could discriminate them from healthy people with a sensitivity of 71% and specificity of 76% (AUC = 0.696, 95% CI: 0.545–0.847, p = 0.011) for the first region and with a sensitivity of 60% and specificity of 85% (AUC = 0.795, 95% CI: 0.689–0.901, p < 0.0001) for the second region. Methylation analysis of the first region of the DICER enabled the distinction of NSCLC patients from healthy individuals with a sensitivity of 96% and specificity of 60% (AUC = 0.651, 95% CI: 0.517–0.785, p = 0.027). The limitations of the study include its small sample size, preliminary nature, being an observational type of study, and the lack of functional experiments allowing for the explanation of the biologic backgrounds of the observed associations. Conclusion: The obtained results indicate that the assessment of DICER and DROSHA methylation status can potentially be used as a biomarker for the early detection of lung cancer.

scholarly journals Torque Teno Virus load in lung cancer patients correlates with age but not with tumor stage

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252304
Author(s):  
Dirk Stefani ◽  
Balazs Hegedues ◽  
Stephane Collaud ◽  
Mohamed Zaatar ◽  
Till Ploenes ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Early Stage ◽  
Stage Iv ◽  
Tumor Stage ◽  
Plasma Dna ◽  
Early Stage Lung Cancer ◽  
Lung Cancer Patients ◽  
Stage Iv Lung Cancer ◽  
Stage Lung Cancer

Background Torque teno virus (TTV) is a ubiquitous non-pathogenic virus, which is suppressed in immunological healthy individuals but replicates in immune compromised patients. Thus, TTV load is a suitable biomarker for monitoring the immunosuppression also in lung transplant recipients. Since little is known about the changes of TTV load in lung cancer patients, we analyzed TTV plasma DNA levels in lung cancer patients and its perioperative changes after lung cancer surgery. Material and methods Patients with lung cancer and non-malignant nodules as control group were included prospectively. TTV DNA levels were measured by quantiative PCR using DNA isolated from patients plasma and correlated with routine circulating biomarkers and clinicopathological variables. Results 47 patients (early stage lung cancer n = 30, stage IV lung cancer n = 10, non-malignant nodules n = 7) were included. TTV DNA levels were not detected in seven patients (15%). There was no significant difference between the stage IV cases and the preoperative TTV plasma DNA levels in patients with early stage lung cancer or non-malignant nodules (p = 0.627). While gender, tumor stage and tumor histology showed no correlation with TTV load patients below 65 years of age had a significantly lower TTV load then older patients (p = 0.022). Regarding routine blood based biomarkers, LDH activity was significantly higher in patients with stage IV lung cancer (p = 0.043), however, TTV load showed no correlation with LDH activity, albumin, hemoglobin, CRP or WBC. Comparing the preoperative, postoperative and discharge day TTV load, no unequivocal pattern in the kinetics were. Conclusion Our study suggest that lung cancer has no stage dependent impact on TTV plasma DNA levels and confirms that elderly patients have a significantly higher TTV load. Furthermore, we found no uniform perioperative changes during early stage lung cancer resection on plasma TTV DNA levels.

scholarly journals Circulating Heat Shock Protein 70 Is a Novel Biomarker for Early Diagnosis of Lung Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Tielong Tang ◽  
Chao Yang ◽  
Ham Ebo Brown ◽  
Jing Huang
Keyword(s):  
Lung Cancer ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Cancer Patients ◽  
Heat Shock Protein 70 ◽  
Early Stage ◽  
Growth And Survival ◽  
Lung Cancer Patients ◽  
Cellular Stresses ◽  
Sensitivity Specificity

Heat shock protein 70 (HSP70) was a highly conserved protein which was significantly induced in response to cellular stresses. HSP70 played an important role in the pathogenesis of cancer which stabilized the production of large amount of oncogenic proteins and finally supported growth and survival of tumor. However, there was no report about the diagnosis of circulating HSP70 in lung cancer patients. In this study, a total of 297 participants (lung cancer: 197, healthy control: 100) were enrolled in the detection of circulating HSP70 level in plasma by ELISA assay. The results indicated that circulating HSP70 significantly decreased in lung cancer patients compared to healthy controls (P<0.0001). Receiver operating characteristic (ROC) analysis showed that HSP70 (AUC: 82.2%, SN: 74.1%, SP: 80.0%) had higher diagnosis value than clinical existing biomarkers CEA (AUC: 80.1%, SN: 76.8%, SP: 67.3%) and CA 19-9 (AUC: 63.7%, SN: 64.2%, SP: 54.0%). In the analysis of early lung cancer patients, ROC results also revealed that HSP70 (AUC: 83.8%, SN: 71.2%, SP: 84.0%) have higher sensitivity, specificity, and AUC than CEA (AUC: 73.7%, SN: 73.2%, SP: 69.1%) and CA 19-9 (AUC: 61.5%, SN: 69.4%, SP: 53.4%). In analysis of specific histological classifications, HSP70 showed more valuable in the diagnosis of SCC (AUC: 85.9%, SN: 86.1.9%, SP: 81.0%) than ADC (AUC: 81.0%, SN: 69.1%, SP: 81.0%). Combined analysis of HSP70 and existing biomarker: CEA and CA 19-9 exhibited that HSP70 combined CEA and CA 19-9 showed the highest AUC (0.945, 95% CI, 0.855–1.000). The importance of our results was that we found decreased circulating HSP70, in combination with elevated CEA and CA 19-9, could be utilized in the diagnosis of early (stage I and II) lung cancer.

Circulating Tumor Cell and Metabolites as Novel Biomarkers for Early-stage Lung Cancer Diagnosis

2020 ◽  
Author(s):  
Lingling Wan ◽  
Yutong He ◽  
Qingyi Liu ◽  
Di Liang ◽  
Yongdong Guo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Early Diagnosis ◽  
Cancer Patients ◽  
Early Stage ◽  
Untargeted Metabolomics ◽  
Early Stage Lung Cancer ◽  
Lung Cancer Patients ◽  
Diagnosis Of Lung Cancer ◽  
Metabolomics Analysis ◽  
Stage Lung Cancer

Abstract Background: Lung cancer is a malignant tumor that has the highest morbidity and mortality rate among all cancers. Early diagnosis of lung cancer is a key factor in reducing mortality and improving prognosis. Methods: In this study, we performed CTC next-generation sequencing (NGS) in early-stage lung cancer patients to identify lung cancer-related gene mutations. Meanwhile, a serum liquid chromatography-tandem mass spectrometry (LC-MS) untargeted metabolomics analysis was performed in the CTC-positive patients, and the early diagnostic value of these assays in lung cancer was analyzed. Results: 62.5% (30/48) of lung cancer patients had ≥ 1 CTC. By CTC NGS, we found that > 50% of patients had 4 commonly mutated genes, namely, NOTCH1, IGF2, EGFR, and PTCH1. 47.37% (9/19) patients had ARIDH1 mutations. Additionally, 30 CTC-positive patients and 30 healthy volunteers were subjected to LC-MS untargeted metabolomics analysis. We found 100 different metabolites, and 10 different metabolites were identified through analysis, which may have potential clinical application value in the diagnosis of CTC-positive early-stage lung cancer (AUC > 0.9). Conclusions: Our results indicate that NGS of CTC and metabolomics may provide new tumor markers for the early diagnosis of lung cancer. This possibility requires more in-depth large-sample research for verification.

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