Comprehensive analysis of Linc01436 for neoadjuvant chemotherapy response and its potential enriched pathways in breast cancer

Abstract

Abstract Background Linc01436 is a novel long non-coding RNA which is associated with tumor proliferation and progression, but its involvement in breast cancer development and neoadjuvant chemotherapy (NAC) response has not been reported. Here, we aimed to explore the association between Linc01436 expression and NAC response as well as their survival outcome in breast cancer patients, and to identify the potential molecular mechanisms of Linc01436 involved in breast cancer. Materials and Methods Univariate and multivariate logistic regression, ROC were used to verify the predictive value of Linc01436 expression in pCR after NAC. Kaplan–Meier curve was utilized to examine the prognostic impact of Linc01436. The Kyoto Encyclopedia of Gene and Genome (KEGG) analysis and Gene Set Enrichment Analysis (GSEA) were conducted to determine the biological processes that Linc01436 may participate in. CIBERSORT, EPIC algorithm were utilized to calculate the proportion of immune-infiltrating cells in TME. IPS score and MANTIS Score were used to assess the immunotherapeutic value of Linc01436. Results The multivariate analysis showed that Linc01436 could predict lower pCR rate of paclitaxel-based NAC in breast cancer (OR = 0.25, P = 0.015, 95% CI: 0.077–0.725), especially in HR negative subtype (OR = 0.16, P = 0.022, 95% CI: 0.029–0.7). The Kaplan–Meier analysis suggested that high Linc01436 expression is associated with poor prognosis in both Renji cohort (HR = 4.58, P = 0.028, 95% CI: 1.51–14.5 ) and TCGA cohort (HR = 1.56, P = 0.033, 95% CI: 1.01–2.41 ). Then, the KEGG and GSEA analysis indicated that Linc01436 was mainly involved in immune related pathways. Further, bioinformatic analysis about the correlation between Linc01436 expression and tumor microenvironment indicated that Linc01436 expression was inversely related to CD8 + T cell infiltration and positively associated with PD-L1 expression and immunotherapy score. Conclusions Our findings indicated that Linc01436 may be a potential inverse predictor for pCR and DFS in breast cancer after NAC, especially for HR negative subgroup. Further, we also shed a broad insight into the molecular signal pathways involved in breast cancer progression and offered an opportunity to optimize the treatment of breast cancer.