Department of Breast and Thyroid Surgery, the First Affiliated Hospital of Hunan Normal University/Hunan Provincial People's Hospital, Changsha 410005, China
Background and Aims The α subunit of pyruvate dehydrogenase E1 component (PDHA1) is the key regulatory site of pyruvate dehydrogenase complex, playing an important role in connecting glycolysis and tricarboxylic acid cycle, and it is of great significance for the metabolic transformation of cancers. The latest research has found a new cell death mechanism, namely cuproptosis. PDHA1 is a gene related to cuproptosis and participates in the regulation of its process. The purpose of this study was to explore the relationship between PDHA1 and the prognosis of breast cancer by using bioinformatics methods and establish a nomogram model related to the prognosis.Methods The clinicopathologic relationship, expression, protein-protein interaction network, gene-gene interaction network, prognostic value, gene set enrichment of PDHA1 in breast cancer were analyzed by using the TCGA, TIMER, UALCAN, HPA, STRING, Gene MANIA, Kaplan-Meier, GEPIA, GeneCards and other databases. The nomogram model was constructed with R language.Results PDHA1 expression was associated with breast cancer T Stage (P<0.001), pathologic stage (P=0.031), race (P<0.001), histological type (P<0.001), PR status (P<0.001), ER status (P<0.001), and PAM50 subtype (P<0.001). TCGA database results showed that the expression level of PDHA1 mRNA in breast cancer tissues was significantly lower than that in normal breast tissues (P<0.001), while UALCAN database results showed that PDHA1 protein was lowly expressed in breast cancer (P<0.001), which was further verified by HPA database. The PPI protein-protein interaction network revealed 15 PDHA1-related interaction proteins. Twenty PDHA1-related interacting genes were obtained from the gene-gene interaction network diagram. Patients in the PDHA1 high-expression group had lower overall survival (HR=1.26, 95% CI=1.02-1.54, P=0.029), relapse-free survival (HR=1.18, 95% CI=1.05-1.32, P=0.005 1), post-progression survival (HR=1.41, 95% CI=1.07-1.86, P=0.015), and metastasis-free survival (HR=1.29, 95% CI=1.1-1.52, P=0.002 3). GSEA results showed that PDHA1 co-expressed genes were mainly involved in the S stage and tricarboxylic acid cycle in breast cancer. Ten compounds related to PDHA1 expression were identified from GeneCards. A nomogram model was constructed by integrating the PDHA1 expression, age, radiation therapy, N stage and M stage, and the calibration chart shows that there was excellent consistency between the nomogram prediction and the actual observation.Conclusion The prognosis of breast cancer patients with high PDHA1 expression is worse than that of patients with low PDHA1 expression. The expression level of PDHA1 is a related factor affecting the prognosis of breast cancer patients. The nomogram model constructed based on PDHA1 expression has certain value in estimating the prognosis of breast cancer patients.
YANG Qiuyi, YI Jianing, GUO Miaolan, FAN Peizhi, YU Jie, ZENG Jie. Relationship between cuproptosis related gene PDHA1 and prognosis of breast cancer and its nomogram construction[J]. Chin J Gen Surg,2022,31(11):1471-1482.