scholarly journals Serum Exosomes and Their miRNA Load—A Potential Biomarker of Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1373
Author(s):  
Mateusz Smolarz ◽  
Piotr Widlak

Early detection of lung cancer in screening programs is a rational way to reduce mortality associated with this malignancy. Low-dose computed tomography, a diagnostic tool used in lung cancer screening, generates a relatively large number of false-positive results, and its complementation with molecular biomarkers would greatly improve the effectiveness of such programs. Several biomarkers of lung cancer based on different components of blood, including miRNA signatures, were proposed. However, only a few of them have been positively validated in the context of early cancer detection yet, which imposes a constant need for new biomarker candidates. An emerging source of cancer biomarkers are exosomes and other types of extracellular vesicles circulating in body fluids. Hence, different molecular components of serum/plasma-derived exosomes were tested and showed different levels in lung cancer patients and healthy individuals. Several studies focused on the miRNA component of these vesicles. Proposed signatures of exosome miRNA had promising diagnostic value, though none of them have yet been clinically validated. These signatures involved a few dozen miRNA species overall, including a few species that recurred in different signatures. It is worth noting that all these miRNA species have cancer-related functions and have been associated with lung cancer progression. Moreover, a few of them, including known oncomirs miR-17, miR-19, miR-21, and miR-221, appeared in multiple miRNA signatures of lung cancer based on both the whole serum/plasma and serum/plasma-derived exosomes.

2015 ◽  
Vol 30 (3) ◽  
pp. 282-285 ◽  
Author(s):  
Xinxin Meng ◽  
Chen Xiao ◽  
Yuguang Zhao ◽  
Lin Jia ◽  
Yang Tang ◽  
...  

Background: MicroRNA-21 (miR-21) has previously been demonstrated as a potential biomarker in diagnosis of various human tumors. This meta-analysis was performed to evaluate the possibility of miR-21 as a biomarker for early detection of lung cancer. Methods: Relevant lung cancer-related miRNA microarray datasets were collected from the NCBI Gene Expression Omnibus (GEO) database and EBI ArrayExpress database up to February 2014. Quality control of the output data was estimated using Limma package and ExiMiR package in R. Standardized mean difference (SMD) with 95% confidence intervals (CIs) from selected datasets was pooled. Heterogeneity was assessed using Cochran's Q test and the I2 statistic, and a p value <0.0.05 or I2 >50% was defined as significant heterogeneity. Furthermore, sensitivity analysis was conducted to evaluate the stability of the pooled results. Four miRNA datasets (GSE24704, GSE17681, GSE27486 and GSE40738) from blood samples were selected, including 153 lung cancer patients and 109 healthy people. Results: The pooled results generated by random-effects model revealed that no significant difference was observed between case and control groups (SMD = 0.58; 95% CI, −0.04 to 1.19; p = 0.07) with significant heterogeneity (p = 0.0032, I2 = 78.2%; p = 0.06). Sensitivity analysis indicated that the results of the meta-analysis were stable. Conclusions: MiR-21 expression levels in whole blood and peripheral blood cells did not show significant differences between lung cancer patients and healthy controls, and it might be ineffective to measure miR-21 expression to achieve an early diagnosis of lung cancer.


Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1069 ◽  
Author(s):  
Sandeep Singhal ◽  
Christian Rolfo ◽  
Andrew W. Maksymiuk ◽  
Paramjit S. Tappia ◽  
Daniel S. Sitar ◽  
...  

Background: Lung cancer is the most common cause of cancer-related deaths worldwide. Early diagnosis is crucial to increase the curability chance of the patients. Low dose CT screening can reduce lung cancer mortality, but it is associated with several limitations. Metabolomics is a promising technique for cancer diagnosis due to its ability to provide chemical phenotyping data. The intent of our study was to explore metabolomic effects and profiles of lung cancer patients to determine if metabolic perturbations in the SSAT-1/polyamine pathway can distinguish between healthy participants and lung cancer patients as a diagnostic and treatment monitoring tool. Patients and Methods: Plasma samples were collected as part of the SSAT1 Amantadine Cancer Study. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify and quantify metabolite concentrations in lung cancer patient and control samples. Standard statistical analyses were performed to determine whether metabolite concentrations could differentiate between healthy subjects and lung cancer patients, as well as risk prediction modeling applied to determine whether metabolic profiles could provide an indication of cancer progression in later stage patients. Results: A panel consisting of 14 metabolites, which included 6 metabolites in the polyamine pathway, was identified that correctly discriminated lung cancer patients from controls with an area under the curve of 0.97 (95% CI: 0.875-1.0). Conclusion: When used in conjunction with the SSAT-1/polyamine pathway, these metabolites may provide the specificity required for diagnosing lung cancer from other cancer types and could be used as a diagnostic and treatment monitoring tool.


2016 ◽  
Vol 13 (3) ◽  
pp. 425-427 ◽  
Author(s):  
Tanya Weinstock ◽  
Pranav Kidambi ◽  
Colleen L. Channick ◽  
Gaetane C. Michaud ◽  
Courtney Broaddus ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2714
Author(s):  
Piotr Widłak ◽  
Karol Jelonek ◽  
Agata Kurczyk ◽  
Joanna Żyła ◽  
Magdalena Sitkiewicz ◽  
...  

Serum metabolome is a promising source of molecular biomarkers that could support early detection of lung cancer in screening programs based on low-dose computed tomography. Several panels of metabolites that differentiate lung cancer patients and healthy individuals were reported, yet none of them were validated in the population at high-risk of developing cancer. Here we analyzed serum metabolome profiles in participants of two lung cancer screening studies: MOLTEST-BIS (Poland, n = 369) and SMAC-1 (Italy, n = 93). Three groups of screening participants were included: lung cancer patients, individuals with benign pulmonary nodules, and those without any lung alterations. Concentrations of about 400 metabolites (lipids, amino acids, and biogenic amines) were measured by a mass spectrometry-based approach. We observed a reduced level of lipids, in particular cholesteryl esters, in sera of cancer patients from both studies. Despite several specific compounds showing significant differences between cancer patients and healthy controls within each study, only a few cancer-related features were common when both cohorts were compared, which included a reduced concentration of lysophosphatidylcholine LPC (18:0). Moreover, serum metabolome profiles in both noncancer groups were similar, and differences between cancer patients and both groups of healthy participants were comparable. Large heterogeneity in levels of specific metabolites was observed, both within and between cohorts, which markedly impaired the accuracy of classification models: The overall AUC values of three-state classifiers were 0.60 and 0.51 for the test (MOLTEST) and validation (SMAC) cohorts, respectively. Therefore, a hypothetical metabolite-based biomarker for early detection of lung cancer would require adjustment to lifestyle-related confounding factors that putatively affect the composition of serum metabolome.


2019 ◽  
Vol 65 (2) ◽  
pp. 224-233
Author(s):  
Sergey Morozov ◽  
Viktor Gombolevskiy ◽  
Anton Vladzimirskiy ◽  
Albina Laypan ◽  
Pavel Kononets ◽  
...  

Study aim. To justify selective lung cancer screening via low-dose computed tomography and evaluate its effectiveness. Materials and methods. In 2017 we have concluded the baseline stage of “Lowdose computed tomography in Moscow for lung cancer screening (LDCT-MLCS)” trial. The trial included 10 outpatient clinics with 64-detector CT units (Toshiba Aquilion 64 and Toshiba CLX). Special low-dose protocols have been developed for each unit with maximum effective dose of 1 mSv (in accordance with the requirements of paragraph 2.2.1, Sanitary Regulations 2.6.1.1192-03). The study involved 5,310 patients (53% men, 47% women) aged 18-92 years (mean age 62 years). Diagnosis verification was carried out in the specialized medical organizations via consultations, additional instrumental, laboratory as well as pathohistological studies. The results were then entered into the “National Cancer Registry”. Results. 5310 patients (53% men, 47% women) aged 18 to 92 years (an average of 62 years) participated in the LDCT-MLCS. The final cohort was comprised of 4762 (89.6%) patients. We have detected 291 (6.1%) Lung-RADS 3 lesions, 228 (4.8%) Lung- RADS 4A lesions and 196 (4.1%) Lung-RADS 4B/4X lesions. All 4B and 4X lesions were routed in accordance with the project's methodology and legislative documents. Malignant neoplasms were verified in 84 cases (1.76% of the cohort). Stage I-II lung cancer was actively detected in 40.3% of these individuals. For the first time in the Russian Federation we have calculated the number needed to screen (NNS) to identify one lung cancer (NNS=57) and to detect one Stage I lung cancer (NNS=207). Conclusions. Based on the global experience and our own practices, we argue that selective LDCT is the most systematic solution to the problem of early-stage lung cancer screening.


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