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Project description:IntroductionSmall cell lung cancer (SCLC) is characterized by poor prognosis and challenging diagnosis. Screening in high-risk smokers results in a reduction in lung cancer mortality, however, screening efforts are primarily focused on non-small cell lung cancer (NSCLC). SCLC diagnosis and surveillance remain significant challenges. The aberrant expression of circulating microRNAs (miRNAs/miRs) is reported in many tumors and can provide insights into the pathogenesis of tumor development and progression. Here, we conducted a comprehensive assessment of circulating miRNAs in SCLC with a goal of developing a miRNA-based classifier to assist in SCLC diagnoses.MethodsWe profiled deregulated circulating cell-free miRNAs in the plasma of SCLC patients. We tested selected miRNAs on a training cohort and created a classifier by integrating miRNA expression and patients' clinical data. Finally, we applied the classifier on a validation dataset.ResultsWe determined that miR-375-3p can discriminate between SCLC and NSCLC patients, and between SCLC and Squamous Cell Carcinoma patients. Moreover, we found that a model comprising miR-375-3p, miR-320b, and miR-144-3p can be integrated with race and age to distinguish metastatic SCLC from a control group.DiscussionThis study proposes a miRNA-based biomarker classifier for SCLC that considers clinical demographics with specific cut offs to inform SCLC diagnosis.
| S-EPMC10585112 | biostudies-literature
Project description:Objectives: Small cell lung cancer (SCLC) is characterized by poor prognosis and challenging diagnosis. Screening in high-risk smokers results in a reduction in lung cancer mortality, however, screening efforts are primarily focused on non-small cell lung cancer (NSCLC). SCLC diagnosis and surveillance remain significant challenges. The aberrant expression of circulating microRNAs (miRNAs/miRs) is reported in many tumors and can provide insights into the pathogenesis of tumor development and progression. Here, we conducted a comprehensive assessment of circulating miRNAs in SCLC with a goal of developing a miRNA-based biomarker classifier to assist in SCLC diagnoses. Materials and Methods: We profiled deregulated circulating cell-free miRNA in the plasma of SCLC patients. We tested selected miRs on a training cohort and created a classifier by integrating miRNA expression and patient clinical data. Finally, we applied the classifier on a validation dataset. Results: We determined that miR-375-3p can discriminate between SCLC and NSCLC patients, and between SCLC and Squamous Cell Carcinoma patients. Moreover, we found that a model comprising miR-375-3p, miR-320b, and miR-144-3p can be integrated with race and age to distinguish metastatic SCLC from a control group. Conclusion: This study proposes a miRNA-based biomarker classifier for SCLC that considers clinical demographics with specific cut offs to inform SCLC diagnosis.
2023-10-31 | GSE240757 | GEO
Project description:Objectives: Small cell lung cancer (SCLC) is characterized by poor prognosis and challenging diagnosis. Screening in high-risk smokers results in a reduction in lung cancer mortality, however, screening efforts are primarily focused on non-small cell lung cancer (NSCLC). SCLC diagnosis and surveillance remain significant challenges. The aberrant expression of circulating microRNAs (miRNAs/miRs) is reported in many tumors and can provide insights into the pathogenesis of tumor development and progression. Here, we conducted a comprehensive assessment of circulating miRNAs in SCLC with a goal of developing a miRNA-based biomarker classifier to assist in SCLC diagnoses. Materials and Methods: We profiled deregulated circulating cell-free miRNA in the plasma of SCLC patients. We tested selected miRs on a training cohort and created a classifier by integrating miRNA expression and patient clinical data. Finally, we applied the classifier on a validation dataset. Results: We determined that miR-375-3p can discriminate between SCLC and NSCLC patients, and between SCLC and Squamous Cell Carcinoma patients. Moreover, we found that a model comprising miR-375-3p, miR-320b, and miR-144-3p can be integrated with race and age to distinguish metastatic SCLC from a control group. Conclusion: This study proposes a miRNA-based biomarker classifier for SCLC that considers clinical demographics with specific cut offs to inform SCLC diagnosis.
2023-10-31 | GSE240758 | GEO
Project description:PurposeRecent screening trial results indicate that low-dose computed tomography (LDCT) reduces lung cancer mortality in high-risk patients. However, high false-positive rates, costs, and potential harms highlight the need for complementary biomarkers. The diagnostic performance of a noninvasive plasma microRNA signature classifier (MSC) was retrospectively evaluated in samples prospectively collected from smokers within the randomized Multicenter Italian Lung Detection (MILD) trial.Patients and methodsPlasma samples from 939 participants, including 69 patients with lung cancer and 870 disease-free individuals (n = 652, LDCT arm; n = 287, observation arm) were analyzed by using a quantitative reverse transcriptase polymerase chain reaction-based assay for MSC. Diagnostic performance of MSC was evaluated in a blinded validation study that used prespecified risk groups.ResultsThe diagnostic performance of MSC for lung cancer detection was 87% for sensitivity and 81% for specificity across both arms, and 88% and 80%, respectively, in the LDCT arm. For all patients, MSC had a negative predictive value of 99% and 99.86% for detection and death as a result of disease, respectively. LDCT had sensitivity of 79% and specificity of 81% with a false-positive rate of 19.4%. Diagnostic performance of MSC was confirmed by time dependency analysis. Combination of both MSC and LDCT resulted in a five-fold reduction of LDCT false-positive rate to 3.7%. MSC risk groups were significantly associated with survival (χ1(2) = 49.53; P < .001).ConclusionThis large validation study indicates that MSC has predictive, diagnostic, and prognostic value and could reduce the false-positive rate of LDCT, thus improving the efficacy of lung cancer screening.
| S-EPMC4876348 | biostudies-literature
Project description:Accumulated evidence indicates that various types of miRNA are aberrantly expressed in lung cancer and secreted into the bloodstream. For this study, we constructed a serum diagnostic classifier based on detailed bioinformatics analysis of miRNA profiles from a training cohort of 143 lung adenocarcinoma patients and 49 healthy subjects, resulting in a 20 miRNA-based classifier. Validation performed with an independent cohort of samples from lung adenocarcinoma patients (n?=?110), healthy subjects (n?=?52), and benign pulmonary disease patients (n?=?47) showed a sensitivity of 89.1% and specificity of 94.9%, with an area under the curve value of 0.958. Notably, 90.8% of Stage I lung adenocarcinoma cases were correctly diagnosed. Interestingly, this classifier also detected squamous and large cell lung carcinoma cases at relatively high rates (70.4% and 70.0%, respectively), which appears to be consistent with organ site-dependent miRNA expression in cancer tissues. In contrast, we observed significantly lower rates (0-35%) using samples from 96 cases of cancer in other major organs, with breast cancer the lowest. These findings warrant a future study to realize its clinical application as a part of diagnostic procedures for lung cancers, for which early detection and surgical removal is presently the only hope for eventual cure.
| S-EPMC4979017 | biostudies-literature
Project description:Small-cell-lung cancer (SCLC) is associated with overexpression of oncogenes including Myc family genes and YAP1 and inactivation of tumor suppressor genes. We performed in-depth proteomic profiling of plasmas collected from 15 individuals with newly diagnosed early stage SCLC and from 15 individuals before the diagnosis of SCLC and compared findings with plasma proteomic profiles of 30 matched controls to determine the occurrence of signatures that reflect disease pathogenesis. A total of 272 proteins were elevated (area under the receiver operating characteristic curve (AUC) ≥ 0.60) among newly diagnosed cases compared to matched controls of which 31 proteins were also elevated (AUC ≥ 0.60) in case plasmas collected within one year prior to diagnosis. Ingenuity Pathway analyses of SCLC-associated proteins revealed enrichment of signatures of oncogenic MYC and YAP1. Intersection of proteins elevated in case plasmas with proteomic profiles of conditioned medium from 17 SCLC cell lines yielded 52 overlapping proteins characterized by YAP1-associated signatures of cytoskeletal re-arrangement and epithelial-to-mesenchymal transition. Among samples collected more than one year prior to diagnosis there was a predominance of inflammatory markers. Our integrated analyses identified novel circulating protein features in early stage SCLC associated with oncogenic drivers.
| S-EPMC8391533 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-12-01 | GSE160241 | GEO
Project description:Soft tissue sarcomas (STS) is a set of rare malignant tumor originated from mesoderm. For the prognosis of sarcoma, early diagnosis is important, however, currently no mature and non-invasive method for diagnosis exists. MicroRNAs (miRNAs) are a class of noncoding RNAs and their expression varies greatly, especially during tumor activity. The purpose of this study was to construct a predictive model for the diagnosis of sarcomas based on the relative expression level of miRNA in serum. miRNA array expression data of 677 samples including 402 malignant sarcoma samples and 275 healthy samples was used to construct the prediction model. Based on 6 gene pairs, random generalized linear model (RGLM) was constructed, with an accuracy of 100% in the internal test dataset and of 74.3% in the merged external dataset in prediction whether a serum sample was obtained from a sarcoma patient, with a specificity of 100% in the internal test dataset and 90.5% in the external dataset. In conclusion, our serum miRNA-pair classifier has the potential to be used for the screening of sarcoma with high accuracy and specificity.
| S-EPMC7365454 | biostudies-literature
Project description:(1) Introduction: The aim of this study was to identify the plasma extracellular vesicle (EV)-specific transcriptional profile in small-cell lung cancer (SCLC) and to explore the application value of plasma EV long RNA (exLR) in SCLC treatment prediction and diagnosis. (2) Methods: Plasma samples were collected from 57 SCLC treatment-naive patients, 104 non-small-cell lung cancer (NSCLC) patients and 59 healthy participants. The SCLC patients were divided into chemo-sensitive and chemo-refractory groups based on the therapeutic effects. The exLR profiles of the plasma samples were analyzed by high-throughput sequencing. Bioinformatics approaches were used to investigate the differentially expressed exLRs and their biofunctions. Finally, a t-signature was constructed using logistic regression for SCLC treatment prediction and diagnosis. (3) Results: We obtained 220 plasma exLRs profiles in all the participants. Totals of 5787 and 1207 differentially expressed exLRs were identified between SCLC/healthy controls, between the chemo-sensitive/chemo-refractory groups, respectively. Furthermore, we constructed a t-signature that comprised ten exLRs, including EPCAM, CCNE2, CDC6, KRT8, LAMB1, CALB2, STMN1, UCHL1, HOXB7 and CDCA7, for SCLC treatment prediction and diagnosis. The exLR t-score effectively distinguished the chemo-sensitive from the chemo-refractory group (p = 9.268 × 10-9) with an area under the receiver operating characteristic curve (AUC) of 0.9091 (95% CI: 0.837 to 0.9811) and distinguished SCLC from healthy controls (AUC: 0.9643; 95% CI: 0.9256-1) and NSCLC (AUC: 0.721; 95% CI: 0.6384-0.8036). (4) Conclusions: This study firstly characterized the plasma exLR profiles of SCLC patients and verified the feasibility and value of identifying biomarkers based on exLR profiles in SCLC diagnosis and treatment prediction.
| S-EPMC9688902 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2012-09-16 | GSE29250 | GEO