Abstract
The metastasis and poor prognosis are still regarded as the main challenge in the clinical treatment of breast cancer (BC). Both N6-methyladenosine (m6A) modification and lncRNAs play vital roles in the carcinogenesis and evolvement of BC. Considering the unknown association of m6A and lncRNAs in BC, this study therefore aims to discern m6A-related lncRNAs and explore their prognostic value in BC patients. Firstly, a total of 6 m6A-related lncRNAs were screened from TCGA database and accordingly constructed a prognostic-predicting model. The BC patients were then divided into high-risk and low-risk groups dependent on the median cutoff of risk score based on this model. Then, the predictive value of this model was validated by the analyses of cox regression, Kaplan-Meier curve, ROC curve, and the biological differences in the two groups were validated by PCA, KEGG, GSEA, immune status as well as in vitro assay. Finally, we accordingly constructed a risk prognostic model based on the 6 identified m6A-related lncRNAs, including Z68871.1, AL122010.1, OTUD6B-AS1, AC090948.3, AL138724.1, EGOT. Interestingly, the BC patients were divided into the low-risk and high-risk groups with different prognoses according to the risk score. Notably, the risk score of the model was an excellent independent prognostic factor. In the clinical sample validation, m6A regulatory proteins were differentially expressed in patients with different risks, and the markers of tumor-associated macrophages and m6A regulators were co-localized in high-risk BC tissues. This well-validated risk assessment tool based on the repertoire of these m6A-related genes and m6A-related lncRNAs, is of highly prognosis-predicting ability, and might provide a supplemental screening method for precisely judging BC prognosis.
Highlights
Breast cancer (BC) represents one of the most fatal malignant tumors prevailed in women, and brings a significant health care burden all over the world
To decipher the potential link of m6A modulators and breast cancer (BC), we analyzed the mRNA expression level of 17 m6Arelated genes, including writer, eraser, and reader in a total of 1066 BC tissues and 112 normal tissues from the The Cancer Genome Atlas (TCGA) database, which showed that 12 out of the 17 m6A-related genes were differentially expressed in BC tissues compared to normal tissues (Figure 2A)
The above results indicated that this group of m6A-related genes might be involved in the tumorigenesis and progression of BC
Summary
Breast cancer (BC) represents one of the most fatal malignant tumors prevailed in women, and brings a significant health care burden all over the world. According to the latest cancer epidemiology survey by the American Cancer Society, the incidence of BC continues to increase by about 0.5% every year, and BC alone will account for 30% of newly diagnosed cancers for women in 2021 [1]. It is welldocumented that BC is a complex tumor type with high genetic heterogeneity, and different BC subtypes display significant biological characteristics and different activities in response to the regimen. Studies have emphasized that the BC signatures with malignant molecular phenotype are more prone to the undesirable prognosis of BC [4,5,6,7]. The establishment of the prognostic risk model could guide the screening and identification of high-risk patients and might help improve clinical outcomes
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