Single‑cell RNA sequencing reveals TMEM71 as an immunomodulatory biomarker predicting immune checkpoint blockade response in breast cancer.

Background: TMEM71 is a poorly characterized transmembrane protein with unclear roles in cancer. This study aimed to explore its prognostic value, immune relevance, and therapeutic implications in breast cancer.

Methods: We integrated transcriptomic, single-cell RNA-seq, immune infiltration and drug response data from TCGA, GTEx, GEO and public scRNA-seq datasets. Prognostic analysis, immune correlation (ssGSEA, CIBERSORT), functional enrichment (GO, KEGG, GSEA) and chemotherapy/immunotherapy sensitivity assessments were conducted.

Results: TMEM71 was significantly downregulated in breast cancer and correlated with poor clinical outcomes. Single-cell analysis revealed its predominant expression in malignant and stromal cells. TMEM71 expression was associated with enhanced infiltration of immune cells, upregulation of immune checkpoints and enrichment of immune-related pathways. High TMEM71 expression predicted better response to immune checkpoint inhibitors (anti-PD-1/PD-L1, anti-CTLA-4) and greater sensitivity to chemotherapeutics, including Gemcitabine, 5-fluorouracil and paclitaxel.

Conclusion: TMEM71 is a novel immune-related gene with potential as a prognostic biomarker and predictor of therapy response in breast cancer. These findings offer new insights into the immunological role of TMEM71 and support its potential utility in guiding personalized treatment strategies.