One hundred thirty-five -related genes were identified as differentially expressed in breast cancer patients.
Forty-two of the identified genes are associated with the survival prognosis of breast cancer patients.
Two subtypes of anoikis-related genes were classified, revealing distinct expression patterns.
Patients with subtype A showed worse survival prognosis and lower immune cell infiltration than those in subtype B.
A set of 10 key anoikis-related genes was linked to poorer breast cancer prognosis.
A nomogram model incorporating gender, age, tumor stage, node stage, and risk score was developed to predict survival outcomes.
Simplified
BACKGROUND: Breast cancer (BC) is the most common cancer in women, and its progression is closely related to the phenomenon of . Anoikis, the specific programmed death resulting from a lack of contact between cells and the extracellular matrix, has recently been recognized as playing a critical role in tumor initiation, maintenance, and treatment. The ability of cancer cells to resist anoikis leads to cancer progression and metastatic colonization. However, the impact of anoikis on the prognosis of BC patients remains unclear.
METHOD: This study utilized data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to collect transcriptome and clinical data of BC patients. Anoikis-related genes (ARGs) were classified into subtypes A and B through consensus clustering. Subsequently, survival prognosis analysis, immune cell infiltration analysis, and functional enrichment analysis were performed for both subtypes. Using the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, a set of 10 ARGs related to prognosis was identified. Immune cell infiltration and tumor microenvironment analyses were conducted on these 10 ARGs to develop a . Furthermore, single-cell data analysis and real-time polymerase chain reaction (RT-PCR) analysis were employed to study the expression of the 10 identified prognostic ARGs in BC cells.
RESULTS: One hundred thirty-five ARGs were identified as differentially expressed genes in the TCGA and GEO databases, with 42 of them associated with the survival prognosis of BC patients. Analyses involving Principal Component Analysis (PCA), t-Distributed Stochastic Neighbor Embedding (t-SNE), and Uniform Manifold Approximation and Projection (UMAP) revealed distinct expression patterns of ARGs between types A and B. Patients in type A exhibited worse survival prognosis and lower immune cell infiltration compared to type B. Subsequent analyses identified 10 key ARGs (YAP1, PIK3R1, BAK1, PHLDA2, EDA2R, LAMB3, CD24, SLC2A1, CDC25C, and SLC39A6) relevant to BC prognosis. Kaplan-Meier analysis indicated that high-risk patients based on these ARGs had a poorer BC prognosis. Additionally, Cox regression analysis established gender, age, T (tumor), N (nodes), and risk score as predictive factors in a nomogram model for BC. The model demonstrated diagnostic value for BC patients at 1, 3, and 5 years. Decision curve analysis (DCA) verified the risk score as a reliable predictor of BC patient survival rates. Moreover, RT-PCR results confirmed differential expressions of YAP1, PIK3R1, BAK1, PHLDA2, CD24, SLC2A1, and CDC25C in BC cells, with SLC39A6, EDA2R, and LAMB3 showing low expression levels.
CONCLUSION: ARGs markers can be used as BC biomarkers for risk stratification and survival prediction in BC patients. Besides, ARGs can be used as stratification factors for individualized and precise treatment of BC patients.
Key numbers
42
ARGs Associated with Prognosis
Out of 135 identified differentially expressed ARGs.
10
Key ARGs for Prognosis
Ten ARGs were selected for the .
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Ethics approval and consent to participate. Databases such as TCGA and GEO are public databases. The patients involved in the database have obtained ethical approval. Users can download relevant data for free for research and publish relevant articles. Our study is based on open-source data, so there are no ethical issues and other conflicts of interest. The authors declare no competing interests.
