Abstract 3661: Non-coding RNAs as biomarkers for early detection of lung cancer
Authors: Casagrande Giovanna Maria Stanfoca , Filho Alessandro Pascon , Siqueira Alexia Polo , Chiarantano Rodrigo Sampaio , Vazquez Fabiana de Lima , Molina Miguel Angel , Pedraz-Valdunciel Carlos , Gimenez-Capitán Ana , Reis Rui Manuel , Leal Leticia Ferro 
Published: March 2024

Introduction: Screening programs proven to reduce lung cancer deaths in high-income countries. Biomarkers detection in body fluids may guide more precise selection of high-risk subjects but this approach has not been currently employed for lung cancer screening. Aims: To identify ncRNA-based signatures for early detection of lung cancer in liquid biopsies. Methods: This is a case-control prospective study, conducted at the Barretos Cancer Hospital Screening Program. We analyzed miRNAs in plasma and sputum samples from high-risk subjects (n=51), and patients (n=44) diagnosed with non-small cell lung cancer (NSCLC), no metastatic, at Barretos Cancer Hospital (Brazil). We analyzed circRNAs in plasma samples from high-risk subjects (n=100), and patients (n=86) with NSCLC at Hospital Universitari Quiron Dexeus (Spain). Samples were subjected to RNA isolation followed expression analysis, for miRNA expression was used nCounter Human V3 microRNA painel, and for circRNA expression was use a nCounter customized painel (NanoString). Counts were normalized by housekeeping, and differentially expressed miRNAs were filtered out according to fold-change (≥|1.5|), p-value (≤0.05). Results: All cancer patients were diagnosed with adenocarcinoma (n=68), squamous cell carcinoma (n=41) and others/no information (n=36). No differences were observed related to age, sex, and tobacco exposure between high-risk and cancer groups (p&gt;0.05). For Brazilian group, we observed six differentially expressed miRNAs in plasma able to distinguish cancer from non-cancer samples - three miRNAs upregulated, and three miRNAs downregulated -, and three of them presented with high accuracy (AUC = 0.70). For sputum, we observed four differentially expressed miRNAs able to distinguish cancer from non-cancer samples, and the 4-miRNA signature present with high accuracy (AUC = 0.73). None of miRNAs were shared between plasma and sputum. In both sample types we have miRNAs associated with zinc finger (ZNF99 and ZNF268), that predicted to be involved in regulation of transcription by RNA polymerase II. In Spanish cohort, we observed 4-circRNA signature with high accuracy (AUC = 0.745). These four circRNAs are associated with insulin resistance and proto-oncogenes. Conclusion: We identified ncRNA-based biomarkers in biofluids potentially to be employed in lung cancer screening programs to better guide selection of high-risk subjects for early detection of lung cancer.

Citation Format: Giovanna Maria Stanfoca Casagrande, Alessandro Pascon Filho, Alexia Polo Siqueira, Rodrigo Sampaio Chiarantano, Fabiana de Lima Vazquez, Miguel Angel Molina, Carlos Pedraz-Valdunciel, Ana Gimenez-Capitán, Rui Manuel Reis, Leticia Ferro Leal. Non-coding RNAs as biomarkers for early detection of lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3661.