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.
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.
Project description:Purpose: We sought to develop and evaluate a diagnostic classifier of UC subtype with the goal of accurate classification from clinically available specimens. Methods: Tumor samples from 52 patients with high-grade UC were profiled for BASE47 genes concurrently by RNAseq as well as NanoString. After design and technical validation of a BASE47 NanoString probeset, results from the RNAseq and NanoString were used to translate diagnostic criteria to the Nanostring platform. Evaluation of repeatability and accuracy was performed to derive a final Nanostring based classifier. Diagnostic classification resulting from the NanoString BASE47 classifier was validated on an independent dataset (n=63). The training and validation datasets accurately classified 87% and 93% of samples, respectively. Results: We have derived a NanoString-platform BASE47 classifier that accurately predicts basal-like and luminal-like subtypes in high grade urothelial cancer. We have further validated our new NanoString BASE47 classifier on an independent dataset and confirmed high accuracy when compared with our original Transcriptome BASE47 classifier. Conclusions: The NanoString BASE47 classifier provides a faster turnaround time, a lower cost per sample to process, and maintains the accuracy of the original subtype classifier for better clinical implementation.
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.