scholarly journals Sensitivity, specificity, and accuracy of a liquid biopsy approach utilizing molecular amplification pools

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jessica Garcia ◽  
Nick Kamps-Hughes ◽  
Florence Geiguer ◽  
Sébastien Couraud ◽  
Brice Sarver ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Clinical Setting ◽  
High Sensitivity ◽  
Sequencing Error ◽  
Lung Cancer Patients ◽  
Mutation Discovery ◽  
Sensitivity Specificity ◽  
Next Generation Sequencing Ngs ◽  
Digital Polymerase Chain Reaction

AbstractCirculating cell-free DNA (cfDNA) has the potential to be a specific biomarker for the therapeutic management of lung cancer patients. Here, a new sequencing error-reduction method based on molecular amplification pools (MAPs) was utilized to analyze cfDNA in lung cancer patients. We determined the accuracy of MAPs plasma sequencing with respect to droplet digital polymerase chain reaction assays (ddPCR), and tested whether actionable mutation discovery is improved by next-generation sequencing (NGS) in a clinical setting. This study reports data from 356 lung cancer patients receiving plasma testing as part of routine clinical management. Sequencing of cfDNA via MAPs had a sensitivity of 98.5% and specificity 98.9%. The ddPCR assay was used as the reference, since it is an established, accurate assay that can be performed contemporaneously on the same plasma sample. MAPs sequencing detected somatic variants in 261 of 356 samples (73%). Non-actionable clonal hematopoiesis-associated variants were identified via sequencing in 21% of samples. The accuracy of this cfDNA sequencing approach was similar to that of ddPCR assays in a clinical setting, down to an allele frequency of 0.1%. Due to broader coverage and high sensitivity for insertions and deletions, sequencing via MAPs afforded important detection of additional actionable mutations.

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.

Diagnostic and prognostic values of circular RNAs for lung cancer: a meta-analysis

2020 ◽  
pp. postgradmedj-2019-137178
Author(s):  
Qian Yang ◽  
Lizhen Chen ◽  
Li Yang ◽  
Yuanshuai Huang
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Area Under The Curve ◽  
High Sensitivity ◽  
Cochrane Library ◽  
Clinicopathological Parameters ◽  
Circular Rnas ◽  
Lung Cancer Patients ◽  
Diagnostic Values

Circular RNAs (circRNAs) may serve as potential biomarkers for patients with lung cancer. The aim of this meta-analysis was to analyse the diagnostic, prognostic and clinicopathological values of circRNAs in lung cancer patients. A systematic search of PubMed, Embase, Web of Science, Scopus and the Cochrane Library databases was performed for relevant articles from inception to 29 January 2020. Pooled parameters including sensitivity, specificity and area under the curve (AUC) were used to assess the diagnostic performance, HRs and 95% CIs were used to evaluate overall survival (OS) and ORs were used to estimate clinicopathological parameters. 52 studies from 45 articles were enrolled in this study, including 17 on diagnosis and 35 on prognosis. For diagnostic values, circRNAs could discriminate lung cancer patients from the controls, with AUC of 0.83 (95% CI: 0.79 to 0.86), a relatively high sensitivity of 0.77 (95% CI: 0.73 to 0.81) and specificity of 0.75 (95% CI: 0.71 to 0.79). For prognostic significances, overexpression of 23 upregulated circRNAs was relevant to a poor prognosis (OS: HR=2.21, 95% CI: 1.96 to 2.49, p<0.001), and overexpression of 9 downregulated circRNAs was correlated with a favourable prognosis (OS: HR=0.62, 95% CI: 0.53 to 0.73, p<0.001). As for clinicopathological parameters, high expression of 23 upregulated circRNAs was associated with unfavourable clinicopathological features while 9 downregulated circRNAs proved the contrary. In conclusion, this study confirmed that circRNAs might serve as important biomarkers for diagnostic and prognostic values of lung cancer.

scholarly journals Distinct gut microbial communities and metabolic functions are associated with cachexia in lung cancer patients

2020 ◽  
Author(s):  
Yueqiong Ni ◽  
Zoltan Lohinai ◽  
Yoshitaro Heshiki ◽  
Balazs Dome ◽  
Judit Moldvay ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Gut Microbiota ◽  
Cancer Patients ◽  
Clinical Setting ◽  
Gut Microbiome ◽  
Microbial Composition ◽  
Shotgun Metagenomics ◽  
Lung Cancer Patients ◽  
Microbial Species ◽  
Functional Pathways

Abstract Background Cachexia is associated with decreased survival in cancer patients and has a prevalence of up to 80%. The etiology of cachexia is poorly understood, and limited treatment options exist. Here, we investigated the role of the human gut microbiome in the clinical setting by integrating shotgun metagenomics and plasma metabolomics of 38 lung cancer patients, with known cachexia status. Results The cachexia group showed significant differences in the gut microbial composition, functional pathways of the metagenome, and the related plasma metabolites compared to non-cachectic patients. Branched-chain amino acids (BCAAs), methylhistamine, as well as vitamins, were significantly depleted in the plasma of cachexia patients, which was also reflected in the depletion of relevant gut microbiota functional pathways. The enrichment of plasma BCAAs and 3-oxocholic acid in non-cachectic patients were positively correlated with the gut microbial species Prevotella copri and Lactobacillus gasseri, respectively. Furthermore, the gut microbiota capacity for lipopolysaccharides biosynthesis was significantly enriched in the cancer cachectic patients. The involvement of gut microbiome in cachexia was further observed in a high-performance machine learning model that uses solely gut microbial taxonomic and pathway features to differentiate cachectic from non-cachectic cancer patients. Conclusions Our study demonstrates the links between host metabolism and specific gut microbial species and functions in a clinical setting, suggesting that the gut microbiota could have an influence on cachexia with possible future therapeutic applications.

Rebiopsy rate for non-small cell lung cancer patients after EGFR-TKI failure in clinical setting: Toward the third-generation EGFR-TKI era.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e19080-e19080 ◽  
Author(s):  
Takahisa Kawamura ◽  
Hirotsugu Kenmotsu ◽  
Kazushige Wakuda ◽  
Akira Ono ◽  
Tetsuhiko Taira ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Clinical Setting ◽  
Small Cell ◽  
Third Generation ◽  
Small Cell Lung ◽  
Lung Cancer Patients ◽  
The Third ◽  
Egfr Tki

scholarly journals Potential Diagnostic and Prognostic Biomarkers of Circular RNAs for Lung Cancer in China

2019 ◽  
Vol 2019 ◽  
pp. 1-17
Author(s):  
Chengdi Wang ◽  
Yuting Jiang ◽  
Qian Lei ◽  
Yangping Wu ◽  
Jun Shao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Predictive Biomarkers ◽  
Diagnostic Value ◽  
Prognostic Biomarkers ◽  
Circular Rnas ◽  
Clinical Value ◽  
Lung Cancer Patients ◽  
Prognostic Analysis ◽  
Sensitivity Specificity

Emerging evidence demonstrated that circular RNAs (circRNAs) were dysregulated in lung cancer, indicating that circRNAs might serve as novel diagnostic and prognostic biomarkers for lung cancer. However, the clinical value of circRNAs on lung cancer remains unclear. This study aimed to evaluate the efficiency of circRNAs in the diagnosis and prognosis for lung cancer in China. 2122 Chinese individuals were enrolled in this investigation for assessment of diagnostic value and examination of prognostic analysis. In the diagnostic analysis, the pooled sensitivity, specificity, PLR, NLR, DOR, and AUC of the sROC curve with their 95% CIs were 0.80 (95%CI: 0.74-0.84), 0.80 (95%CI: 0.73-0.86), 3.97 (95%CI: 2.80-5.62) and 0.26 (95%CI: 0.19-0.34), 15.51 (95%CI: 8.76-24.47), and 0.85 (95%CI: 0.82-0.88), respectively. As for the prognostic power of circRNAs, lung cancer patients with higher expression levels of circRNAs tend to possess lower overall survival with the overall pooled HR (1.70, 95%CI: 1.26-2.29). Furthermore, in stratified analysis, upregulated and downregulated circRNAs were manifested to exert significant effects on prognosis with HR values of 2.17 (95%CI: 1.74-2.72) and 0.52 (95%CI: 0.34-0.80). This study validates that circRNAs are promising diagnostic and predictive biomarkers for lung cancer patients in China.

scholarly journals Clinical Characteristics and Molecular Patterns of RET-Rearranged Lung Cancer in Chinese Patients

2019 ◽  
Vol 27 (5) ◽  
pp. 575-582 ◽  
Author(s):  
Kai Zhang ◽  
Huajun Chen ◽  
Ye Wang ◽  
Lin Yang ◽  
Chengzhi Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Clinical Characteristics ◽  
Progression Free Survival ◽  
Chinese Patients ◽  
Lung Cancers ◽  
Lung Cancer Patients ◽  
Molecular Features ◽  
Molecular Patterns ◽  
Next Generation Sequencing Ngs

RET rearrangement has been proven as an oncogenic driver in patients with lung cancer. However, the prevalence, clinical characteristics, molecular features, and therapeutic options in RET-rearranged patients remain unclear, especially in Chinese lung cancer patients. We retrospectively collected 6,125 Chinese lung cancer patients who have been profiled using next-generation sequencing (NGS). The clinical demographics and molecular features of RET rearrangement-positive patients were analyzed. RET rearrangements were identified in 84 patients with a proportion of 1.4% in our cohort. The median age at diagnosis was 58 years, and it mainly occurred in females with adenocarcinoma histology. KIF5B-RET was the most frequent fusion type and accounted for 53.8% (57/106) of all RET fusions identified, with K15-R12 as the most frequent variant (71.9%). Among 47 RET+ patients profiled with larger panels, 72.3% (34/47) harbored concurrent alterations. TP53 ranked as the most common concurrent alteration, and concomitant EGFR oncogenic alterations were identified in seven patients. Moreover, an adenocarcinoma patient harboring concurrent RET fusion and EGFR L858R responded to combinatorial treatment of cabozantinib and osimertinib, with a progression-free survival of 5 months. Our study improved knowledge of clinical characteristics and molecular features of RET-rearranged lung cancers in China. It might be helpful to guide clinicians for more effective personalized diagnostic and therapeutic approaches.

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