ABSTRACT
Breast cancer is the most common cancer in women. Over the past few decades, advances in cancer detection and treatment have significantly improved survival rate of breast cancer patients. However, due to the cardiovascular toxicity of cancer treatments (chemotherapy, anti-HER2 antibodies and radiotherapy), cardiovascular diseases (CVD) have become an increasingly important cause of long-term morbidity and mortality in breast cancer survivors. Endocrine therapies are prescribed to reduce the risk of recurrence and specific death in estrogen receptor-positive (ER +) early breast cancer patients, but their impact on CVD is a matter of debate. Whereas aromatase inhibitors and luteinizing hormone-releasing hormone (LHRH) analogs inhibit estrogen synthesis, tamoxifen acts as a selective estrogen receptor modulator (SERM), opposing estrogen action in the breast but mimicking their actions in other tissues, including arteries. This review aims to summarize the main clinical and experimental studies reporting the effects of tamoxifen on CVD. In addition, we will discuss how recent findings on the mechanisms of action of these therapies may contribute to a better understanding and anticipation of CVD risk in breast cancer patients.
Subject(s)
Breast Neoplasms , Cardiovascular Diseases , Female , Humans , Tamoxifen/adverse effects , Antineoplastic Agents, Hormonal/adverse effects , Chemotherapy, Adjuvant , Estrogens , Cardiovascular Diseases/chemically induced , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/drug therapy , Arteries , Selective Estrogen Receptor Modulators/adverse effectsABSTRACT
BACKGROUND: Cervical cancer (CC) is one of the most common female cancers in many developing and underdeveloped countries. High incidence, late presentation, and mortality suggested the need for molecular markers. Mitochondrial defects due to abnormal expression of nuclear-encoded mitochondrial genes (NEMG) have been reported during cancer progression. Nevertheless, the application of NEMG for the prognosis of CC is still elusive. Herein, we aimed to investigate the associations between NEMG and CC prognosis. MATERIALS AND METHODS: The differentially expressed genes (DEG) in the TCGA-CESC dataset and NEMGs were retrieved from TACCO and Mitocarta2.0 databases, respectively. The impact of methylation on NEMG expression were predicted using DNMIVD and UALCAN tools. HCMDB tool was used to predict genes having metastatic potential. The prognostic models were constructed using DNMIVD, TACCO, GEPIA2, and SurvExpress. The functional enrichment analysis (FEA) was performed using clusterProfiler. The protein-protein interaction network (PPIN) was constructed to identify the hub genes (HG) using String and CytoHubba tools. Independent validation of the HG was performed using Oncomine and Human Protein Atlas databases. The druggable genes were predicted using DGIdb. RESULTS: Among the 52 differentially expressed NEMG, 15 were regulated by DNA methylation. The expression level of 16, 10, and 7 has the potential for CC staging, prediction of metastasis, and prognosis. Moreover, 1 driver gene and 16 druggable genes were also identified. The FEA identified the enrichment of cancer-related pathways, including AMPK and carbon metabolism in cancer. The combined expression of 10 HG has been shown to affect patient survival. CONCLUSION: Our findings suggest that the abnormal expression of NEMGs may play a critical role in CC development and progression. The genes identified in our study may serve as a prognostic indicator and therapeutic target in CC.
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