Construction and validation of immune-associated lncRNA model for predicting immune status and therapeutic reactions of triple-negative breast cancer.

OBJECTIVE

The immune status of the tumor microenvironment significantly impacts the clinical prognosis of triple-negative breast cancer (TNBC). The involvement of long noncoding RNAs (lncRNAs) in tumor immune infiltration is widely acknowledged. Therefore, it is crucial to explore the role of significant immune-related lncRNAs in TNBC.

METHODS

We acquired RNA, single-cell sequencing, and clinical information on TNBC from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. To identify immune-related lncRNAs, immune infiltration subgroups were determined and verified using single-sample gene-set enrichment analysis, non-negative matrix factorization, and weighted gene co-expression network analysis. CIBERSORTx, deconvolution, drug sensitivity, and Scissor analyses revealed that differences in cell type and drug efficacy were associated with immune grouping.

RESULTS

TNBC samples were classified into immune-desert (cold) and immune-inflamed (hot) subgroups based on a lncRNA model (including LINC01550, LY86-AS1, LINC00494, LINC00877, CHRM3-AS2, HCP5, MIR155HG, and PIK3CD-AS1). Furthermore, using in vitro experiments, we found that LINC01550 promoted malignant phenotypes, including proliferation, survival, and migration of TNBC. The immune-inflamed subgroup exhibited significantly lower half-maximal inhibitory concentration values for common anti-tumor drugs, including palbociclib, ribociclib, mitoxantrone, and sorafenib (T-test, P < 0.001). This may be related to the fact that the immune-inflamed subgroup has more plasmacytoid dendritic cells (pDCs) and B cells than those in immune-desert subgroups (P < 0.001).

CONCLUSIONS

Differences in specific cell infiltration can lead to increased sensitivity of the immune-inflamed subgroup to anti-tumor drugs. The proposed lncRNA model holds great promise to assess the immune landscapes and therapeutic reactions of TNBC patients.