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BACKGROUND: Previously reported breast invasive carcinoma (BRIC) biomarkers have compromised utility because of their heterogeneity-specific behaviors. The goal of this study was to find BRIC biomarkers that could be used in spite of the heterogeneity barrier. METHODS: Previously reported BRIC-linked hub genes were obtained from the literature via a search technique. A protein-protein interaction (PPI) network of the extracted hub genes was constructed, visualized, and analyzed to explore the top six real hub genes. Following this, real hub genes' expression profiling was carried out using various TCGA data sources and RNA sequencing (RNA-seq) of BT 20 and HMEC cell lines to uncover the tumor-driver roles of the real hub genes. RESULTS: In total, 124 BRIC-linked hub genes were collected from the literature via the search technique. From these collected hub genes, a total of 6 genes, including Centrosomal protein of 55 kDa (CEP55), Kinesin Family Member 2C (KIF2C), kinesin family member 20A (KIF20A), Ribonucleotide Reductase Regulatory Subunit M2 (RRM2), Aurora A Kinase (AURKA), and Protein Regulator of cytokinesis 1 (PRC1) were determined to be the real hub genes. Via expression profiling and validation analyses, we documented the overexpression of CEP55, KIF2C, KIF20A, RRM2, AURKA, and PRC1 real hub genes in BRIC patients with different clinical variables. Further correlational analyses showed diverse associations among real hub genes' expression and other important parameters, including promoter methylation status, genetic alteration, overall survival (OS), relapse-free survival (RFS), tumor purity, CD8+ T, CD4+ T immune cell infiltration, and different mutant genes across BRIC samples. Finally, in this work, we investigated several transcription factors (TFS), microRNAs, and therapeutic medicines related to the real hub genes that have great therapeutic potential. CONCLUSION: In conclusion, we discovered six real hub genes, which may be employed as novel potential biomarkers for BRIC patients with different clinical parameters.
RESUMO
Background Neonatal sepsis includes numerous systemic illnesses such as septicemia, meningitis, urinary tract infections, and pneumonia. In developing countries, the major reason for neonatal mortality is septicemia, which accounts for almost 50% of overall deaths. Thrombocytopenia is one of the most common hematological problems during the neonatal period, affecting the majority of sufferers admitted to the neonatal intensive care unit (NICU). The aim of our study was to find the frequency of thrombocytopenia and its severity in neonates with sepsis. Methods The study was conducted at the Department of Hematology at Khyber Medical University, Peshawar, Pakistan. A total of 170 neonates with an age of fewer than 28 days, both genders, and positive blood cultures were included in the study using a non-probability consecutive sampling technique. Data was recorded in predesigned questionnaires after taking informed consent. Data were recorded and analyzed using SPSS version 26 (IBM Corporation, Armonk, NY, USA). Results Of the 170 neonates, 104 (61.2%) were males, with a mean age of 12.12±8.88 days. The majority of the babies 73 (42.9%) were in the age group of 0-7 days. Most of the neonates 72 (42.4%) were born via normal vaginal delivery (NVD). Of the neonates, 117 (68.82%) presented with fever, and 105 (61.76%) were reluctant to feed. Furthermore, 65.29% of the neonates had thrombocytopenia, of which 34 (20%) had mild, 43 (25.3%) had moderate, and 34 (20%) had severe thrombocytopenia. In neonates with positive blood culture, the platelet level was low (p<0.001). In the case of gram-negative organisms, the level of platelets was lower as compared to gram-positive organisms (p<0.001). Conclusion Sepsis is still a common cause of newborn thrombocytopenia. The fact that it is present in more than half of all culture-positive sepsis episodes indicates the severity of the condition. This condition is further defined by higher percentages of early-onset gram-negative septicemia compared to gram-positive sepsis.
