TY - JOUR
T1 - Serum Insights
T2 - Leveraging the Power of miRNA Profiling as an Early Diagnostic Tool for Non-Small Cell Lung Cancer
AU - Charkiewicz, Radoslaw
AU - Sulewska, Anetta
AU - Mroz, Robert
AU - Charkiewicz, Alicja
AU - Naumnik, Wojciech
AU - Kraska, Marcin
AU - Gyenesei, Attila
AU - Galik, Bence
AU - Junttila, Sini
AU - Miskiewicz, Borys
AU - Stec, Rafal
AU - Karabowicz, Piotr
AU - Zawada, Magdalena
AU - Miltyk, Wojciech
AU - Niklinski, Jacek
PY - 2023/10/10
Y1 - 2023/10/10
N2 - Non-small cell lung cancer is the predominant form of lung cancer and is associated with a poor prognosis. MiRNAs implicated in cancer initiation and progression can be easily detected in liquid biopsy samples and have the potential to serve as non-invasive biomarkers. In this study, we employed next-generation sequencing to globally profile miRNAs in serum samples from 71 early-stage NSCLC patients and 47 non-cancerous pulmonary condition patients. Preliminary analysis of differentially expressed miRNAs revealed 28 upregulated miRNAs in NSCLC compared to the control group. Functional enrichment analyses unveiled their involvement in NSCLC signaling pathways. Subsequently, we developed a gradient-boosting decision tree classifier based on 2588 miRNAs, which demonstrated high accuracy (0.837), sensitivity (0.806), and specificity (0.859) in effectively distinguishing NSCLC from non-cancerous individuals. Shapley Additive exPlanations analysis improved the model metrics by identifying the top 15 miRNAs with the strongest discriminatory value, yielding an AUC of 0.96 ± 0.04, accuracy of 0.896, sensitivity of 0.884, and specificity of 0.903. Our study establishes the potential utility of a non-invasive serum miRNA signature as a supportive tool for early detection of NSCLC while also shedding light on dysregulated miRNAs in NSCLC biology. For enhanced credibility and understanding, further validation in an independent cohort of patients is warranted.
AB - Non-small cell lung cancer is the predominant form of lung cancer and is associated with a poor prognosis. MiRNAs implicated in cancer initiation and progression can be easily detected in liquid biopsy samples and have the potential to serve as non-invasive biomarkers. In this study, we employed next-generation sequencing to globally profile miRNAs in serum samples from 71 early-stage NSCLC patients and 47 non-cancerous pulmonary condition patients. Preliminary analysis of differentially expressed miRNAs revealed 28 upregulated miRNAs in NSCLC compared to the control group. Functional enrichment analyses unveiled their involvement in NSCLC signaling pathways. Subsequently, we developed a gradient-boosting decision tree classifier based on 2588 miRNAs, which demonstrated high accuracy (0.837), sensitivity (0.806), and specificity (0.859) in effectively distinguishing NSCLC from non-cancerous individuals. Shapley Additive exPlanations analysis improved the model metrics by identifying the top 15 miRNAs with the strongest discriminatory value, yielding an AUC of 0.96 ± 0.04, accuracy of 0.896, sensitivity of 0.884, and specificity of 0.903. Our study establishes the potential utility of a non-invasive serum miRNA signature as a supportive tool for early detection of NSCLC while also shedding light on dysregulated miRNAs in NSCLC biology. For enhanced credibility and understanding, further validation in an independent cohort of patients is warranted.
KW - miRNA
KW - Shapley Additive exPlanations
KW - gradient-boosting decision tree classifier
KW - next-generation sequencing
KW - biomarkers
KW - liquid biopsy
KW - non-small cell lung cancer
U2 - 10.3390/cancers15204910
DO - 10.3390/cancers15204910
M3 - Article
C2 - 37894277
SN - 2072-6694
VL - 15
JO - Cancers
JF - Cancers
IS - 20
M1 - 4910
ER -