Abstract 3355: FTO in smoking-associated lung cancer and lung cancer tumor progression

Abstract In 2024, an estimated 234,580 patients will be diagnosed with lung cancer and 125,070 are expected to die, making lung cancer the leading cause of cancer-related deaths. Early detection of lung cancer is critical for improving prognosis, hence the need for early detection biomarkers. Fat mass and obesity-associated gene (FTO) had earlier been linked with obesity, however current studies indicate it may have a role in tumor development and could be a potential biomarker. In this study, we aimed to identify a possible link between FTO and non-small cell lung cancer (NSCLC), which accounts for 85% of lung cancer diagnosis. We hypothesize FTO is involved in increasing tumorigenicity and mortality among lung cancer patients. The role of FTO was studied in tumor progression, patient survival analysis, and smoking induced lung cancer, which is not established. Using immunohistochemistry, 115 tumor sections of NSCLC patients were studied; of these patients, 64 were early-stage NSCLC and 51 were late-stage. Patient tissues were obtained from local hospital pathology archives. Staining was completed using FTO primary antibody and a biotinylated secondary antibody. FTO brightness scores were generated using the BZX-800 analyzer software. FTO expression was also calculated using an H-score with the help of a pathologist. Both imaging studies and pathology grading indicated that late-stage lung cancer tissues had significantly (p<0.05) higher FTO expression compared to early-stage cases. When subdivided into low and high expression levels, 69% of early-stage tissue samples exhibited low expression levels and 55% of late-stage tumor tissues had high FTO expression. To assess the role of FTO expression in lung cancer survival, a Kaplan-Meier analysis was done with 47 patients. Results showed that NSCLC patients with higher expression had a shorter median survival time (14 months) compared to NSCLC patients with low expression (27 months) (p=0.03). These results suggest that patients with higher FTO expression may have poorer prognosis. Since 80-90% of lung cancer patients had a history of smoking, we studied the connection between FTO expression and smoking associated lung cancer. 50 NSCLC tumor sections were stained, 28 being smokers and 22 being non-smokers. The average FTO expression level was 24% higher in smokers compared to non-smokers (p<0.02). Using H-scores, smokers were divided into low and high expression levels. 93% of smokers had a high FTO expression compared to 7% in non-smokers indicating that smokers had higher expression of FTO compared to non-smokers (P=0.001). In conclusion, FTO may have a role in tumor progression as it is highly expressed in late-stage lung tumor tissues. High expression of FTO is also a potential indicator of patient survival, as patients who had an upregulation of FTO had shorter survival time. Finally, we found a possible link between high FTO expression and smoking-induced lung cancer. Citation Format: Rachel Campoli, Rong Qiu, Robert Hillwig, Neelu Puri. FTO in smoking-associated lung cancer and lung cancer tumor progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3355.