Abstract Background: The identification of prognostic biomarkers in triple-negative breast cancer (TNBC) is critical for optimizing therapeutic strategies in this aggressive subtype. Bulk RNA sequencing enables comprehensive transcriptomic profiling that encompasses both coding and non-coding regions, thereby offering a more integrative view of TNBC biology. Within the non-coding transcriptome, long non-coding RNAs (lncRNAs) have emerged as candidate biomarkers due to their roles in the regulation of gene expression. However, additional evidence is needed to validate their prognostic relevance specifically in the context of early-stage TNBC. Methods: Bulk RNA-seq analysis was performed on FFPE diagnostic core-biopsies from TNBC patients obtained prior to neoadjuvant systemic treatment with 6 cycles of docetaxel-carboplatin (NACT). Sequences annotation was conducted using STAR (v.2.7.9a) and SALMON (v.1.6.0) software, and data was analysed attending differential expression analysis associated with response to NACT in the surgical specimen. The analysis was performed using Wald test, and the regulatory expression associations between coding and non-coding elements were evaluated using Pearson’s correlation analysis. Results: Transcript biotype analysis in TNBC patients classified as responders (pCR, N=140) and non-responders (RCB I-II-III, N = 141) to NACT showed a high proportion of non-coding elements, with a predominance of lncRNAs and pseudogenes. Interestingly, the non-pCR group exhibited a marked absence of immunoglobulin (IG) and T-cell receptor (TCR) transcripts compared to the pCR group. Differential expression analysis identified 166 lncRNA significantly deregulated between groups, among which PMSB8-AS1 emerged as a candidate prognostic biomarker, showing significant association with event-free survival (EFS) in Kaplan Meier analysis (p0.05). Besides, PMSB8-AS1 and LINC00996 expression correlated with the expression of immunerelated genes ITK, ITGAL, GPR174, and SASH3, of which ITK and GPR174 are important for T-cell activation, ITGAL encodes CD11A, and SASH3 is also expressed by lymphocytes but its function is unknown. These genes are independent of the basal-like subtype and showed significant associations with EFS and distant free survival (DRFS). Additionally, ITGAL was also associated with overall survival (OS). In multivariate clinicopathological analysis (covariates: cT, cN, Ki67, PAM50 subtype, TILs, and pathological response), PMSB8-AS1 remained significantly associated with EFS (p 0.05), while PMSB8-AS1 and LINC00996 signature was associated with EFS and OS (p 0.05) and showed a trend for DRFS (p= 0,08). Conclusions: Our findings suggest that PMSB8-AS1 may be an early biomarker of EFS and a surrogate of immune and T-cell activation in TNBC through the regulation of the expression of ITK, ITGAL, GPR174, and SASH3 genes, supported by the absence of IG and TCR expression in non-responders before NACT. The combined expression of PMSB8-AS1 and LINC00996 improves EFS and OS risk prediction when integrated with clinicopathological variables such as cT, cN, Ki67, PAM50 subtype, TILs, and pathological response. Further functional validation is needed to confirm their role in immune modulation. Citation Format: S. López-Tarruella, C. Polo, E. Alvarez, Y. Jerez, I. Echavarria, M. del Monte-Millán, B. Herrero, P. Jara, F. Moreno Antón, J. García-Sáenz, C. Bueno, M. Bringas, I. Márquez-Rodas, A. Ballesteros, N. Jiménez-Alduán, A. López de Sa, H. Gómez Moreno, H. Fuentes, A. Barnadas, A. Prat, B. Peláez-Lorenzo, R. Martín Lozano, A. Sánchez de Torre, M. Cebollero, T. Massarrah, I. Ocaña, A. Arias, L. Villarejo, V. Cañadilla, F. Ayala de la Peña, M. Martín. Transcriptomic Profiling Reveals PMSB8-AS1 and LINC00996 as Potential Prognostic Biomarkers in Triple-Negative Breast Cancer Treated with Neoadjuvant Docetaxel-Carboplatin abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PD7-04.
López-Tarruella et al. (Tue,) studied this question.