Cuproptosis- and m6A-related lncRNA prognostic signature for breast cancer, in which Z68871.1 contributes to triple-negative breast cancer progression.

Breast cancer (BC) has the second-highest global incidence rate among all cancers and poses a great threat to human health. Cuproptosis, a newly discovered type of cell death, is expected to become a promising target for cancer therapy. Moreover, N6-methyladenosine (m6A) modification has been shown to be involved in a variety of cell death pathways that affect malignant tumor development; however, the relationship between cuproptosis and m6A modification remains unclear. Here, we investigated the relationship between cuproptosis and m6A modification. An 8-lncRNA signature (AC009053.3, AC017071.1, MFF-DT, RNF213-AS1, AC091588.1, AL118556.1, Z68871.1, AL451123.1) related to cuproptosis and m6A was constructed to predict the prognosis of BC patients. The prognostic signature achieved good predictive performance and was an independent predictor of prognosis for BC patients. On the basis of the risk scores, we divided the BC patients into high- and low-risk groups. Patients in the high-risk group had worse outcomes and higher tumor mutation burdens and somatic mutation frequencies than those in the low-risk group did. High risk scores were also associated with the suppression of tumor immunity. In addition, we confirmed the expression and prognostic value of these 8 lncRNAs in different subtypes of BC. The results showed that Z68871.1 promoted the progression of triple-negative breast cancer (TNBC) by regulating cuproptosis, m6A modification and tumor immunity via the RBM15/YTHDC2/Z68871.1/ATP7A axis. In conclusion, the signature we constructed serves as an accurate, independent and specific prognostic model for BC patients, and Z68871.1 could be a promising therapeutic target for TNBC.