Pro-inflammatory and autophagic pathways in lung cancer: dysregulation of key genes ADINR, C/EBPα, CHAST, ATG5, IL-1B, and DICER1-AS1

Purpose Lung cancer is the second most prevalent malignancy in both sexes and remains the leading cause of cancer-related mortality. This study aimed to evaluate the expression profile of selected Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling-related genes and long non-coding RNAs (lncRNAs), particularly those involved in pro-inflammatory and autophagic pathways, in lung cancer tissues. Methods The expression levels of three NF-κB-associated-mRNA coding genes (CCAAT/enhancer-binding protein alpha (C/EBPα), Autophagy Protein 5 (ATG5) and Interleukin-1b (IL-1B)) and six lncRNAs (Antisense Noncoding RNA in the INK4 Locus (ANRIL), Adipogenic Differentiation-Induced Noncoding RNA (ADINR), Cardiac Hypertrophy-Associated Transcript (CHAST), DICER1 Antisense RNA 1 (DICER1-AS1), Hepatocellular Carcinoma Up-regulated Long Non-coding RNA (HULC) and NF-κB Interacting LncRNA (NKILA)) from this pathway were assessed in 42 pairs of lung cancer samples and adjacent non-tumoral tissues. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of these transcripts in distinguishing tumoral from non-tumoral samples. Results ADINR, C/EBPα, CHAST, ATG5, IL-1B, and DICER1-AS1 were significantly up-regulated in tumor samples compared with adjacent non-tumoral tissues. Among the studied genes, C/EBPα showed the highest level of up-regulation in tumor tissues, with an expression ratio of 412 (95% confidence interval (CI): 159–1075, P < 0.0001). ROC curve analysis showed that the diagnostic accuracy of the evaluated transcripts ranged from 94.12% for C/EBPα to 72.26% for ADINR. The highest positive predictive value and negative predictive value were observed for C/EBPα, at 93.02% and 95.12%, respectively. The Area Under Curve (AUC) values were 0.95 for C/EBPα, 0.84 for IL-1B, 0.79 for CHAST, 0.77 for DICER1-AS1, and 0.74 for ADINR. Conclusion The present study indicates up-regulation of NF-κB-related pro-inflammatory and autophagy-associated transcripts in lung cancer tissues. Our findings suggest that these transcripts, particularly C/EBPα, show differential expression patterns that warrant further investigation as candidate tissue biomarkers. However, the translational impact of this study is limited by lack of functional studies. Independent validation and comparison with existing clinical diagnostics are required before any clinical application can be considered.