Abstract 3679: Development and validation of prognostic signatures comprising neutrophil-specific long non-coding RNAs (LncRNAs) for predicting survival in urothelial carcinoma
Authors: Su Harvey Yu-Li , Lin Chang-Ting , Huang Shih-Yu , Chen Yi-Hua , Kuo Chung-Wen 
Published: March 2024

Background: Tumor-associated neutrophils profoundly influence the tumor immune microenvironment (TME), impacting urothelial carcinoma (UC) progression, metastasis, and survival. Long non-coding RNAs (lncRNAs) have emerged as critical players in cancer biology. Recognizing neutrophils as influential contributors to tumor biology, our study aimed to explore neutrophil-specific lncRNAs and evaluate their prognostic significance in UC.

Methods: In the GSE24890 dataset, 46 lncRNAs were identified with elevated expression in neutrophils compared to other immune cells, thus designating them as neutrophil-specific lncRNAs. To establish a tailored prognostic model, the TCGA BLCA dataset served as the internal training set. Candidate lncRNAs underwent filtration and selection through univariate Cox regression analysis, followed by the construction of a risk score employing LASSO and multivariate Cox regression algorithms. We used IMVigor210 dataset as external validation for this lncRNA model.

Results: Ten lncRNAs exhibiting correlation with overall survival (OS) were initially identified through univariate Cox regression. Following LASSO regression and subsequent multivariate Cox regression analysis, a refined set of 9 lncRNAs was selected to construct the risk model, represented by the formula: Risk score = (-0.096 × FAM13A-AS1 expression level) + (0.157 × FAM27C expression level) + (-0.294 × HCG27 expression level) + (-0.037 × HOTAIRM1 expression level) + (-0.137 × LINC-PINT expression level) + (-0.279 × LINC00612 expression level) + (-0.058 × LINC00967 expression level) + (0.187 × LINC01018 expression level) + (-0.288 × LINC01138 expression level). Kaplan-Meier survival analysis of the BLCA cohort revealed that patients in the high-risk group experienced significantly worse OS compared to those in the low-risk group (p &lt; 0.001). The area under the curve (AUC) values at 1, 3, and 5 years were 0.66, 0.67, and 0.66, respectively. In the multivariate Cox regression model, the risk score remained an independent prognostic factor (p &lt; 0.001; HR 2.5; 95% CI 1.91-3.30). The validity of the risk score was further confirmed in the IMVigor210 dataset, demonstrating discriminative predictive ability for OS between high- and low-risk groups (p = 0.027).

Conclusions: This study underscores the interplay between neutrophils and lncRNAs in UC. Neutrophil-related lncRNAs identified may serve as promising therapeutic targets and prognostic markers for UC.

Citation Format: Harvey Yu-Li Su, Chang-Ting Lin, Shih-Yu Huang, Yi-Hua Chen, Chung-Wen Kuo. Development and validation of prognostic signatures comprising neutrophil-specific long non-coding RNAs (LncRNAs) for predicting survival in urothelial carcinoma [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 3679.