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Introduction Cyclin-dependent kinase inhibitor 2A (CDKN2A) is a suppressor carcinogenic gene that is upregulated across various types of cancer including breast, liver, thyroid, and bile duct cancer due to its crucial role in cell cycle regulation and cell division. Nevertheless, it is mostly investigated at the genetic level, but it is still poorly studied on pan-cancer analysis as a biomarker and this study shows its significant potential diagnostic and prognostic characteristics. However, this study aims to investigate the role of CDKN2A as a diagnostic and prognostic biomarker across various types of cancer focusing primarily on colon adenocarcinoma (COAD). Methods We investigated CDKN2A gene expression in a pan-cancer analysis across different types of cancer to show its diagnostic potential characteristics by using various bioinformatic tools, including Tumor Immune Estimation Resource (TIMER) 2.0, Gene Expression Profiling Interactive Analysis (GEPIA), and University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) database. TIMER was used to profile gene expression across 32 types of cancer composed of 10,000 RNA-seq samples obtained from the Cancer Genome Atlas (TCGA) and to analyze the tumor-infiltrating immune cells. In addition, GEPIA and UALCAN were further used to analyze gene expression, in terms of gene regulation, pathological stages, and clinical parameters, including gender, age, and race. Therefore, we used GEPIA, UALCAN, and Kaplan-Meier plotter particularly across adenocarcinoma to investigate CDKN2A prognosis by studying its high expression association with the patient's overall survival rate to show the tumor progression. Then, we looked into the genetic alteration of CDKN2A by using the cBio Cancer Genomics Portal (cBioPortal), including 10 pan-cancer studies. We concluded the analysis with gene validation by using a public cohort in Gene Expression Omnibus (GEO). Results CDKN2A showed a trend of upregulation in most cancers and it was significantly upregulated in five cancers, which were commonly identifiable in three databases, including breast invasive carcinoma (p < 0.001), kidney chromophobe (p < 0.001), kidney renal clear cell carcinoma (p < 0.001), kidney renal papillary cell carcinoma (p < 0.001), and COAD (p < 0.001). The upregulation was significantly different in association with pathogenic stages II and III (pr(>F) = 0.00234) which was identifiable significantly in COAD more than in other cancers. The gene showed a high upregulation in association with poor prognosis of patient survival in three cancers, including COAD (log-rank p = 0.011), mesothelioma (log-rank p = 5.9e-07), and liver hepatocellular carcinoma (log-rank p = 0.0045). Therefore, COAD was the only comprehensively analyzed tumor to show a diagnostic and prognostic potential characteristic during high upregulation of CDKN2A. Furthermore, CDKN2A displayed a rare mutation in the form of deep deletion (9%) and revealed an upregulation associated with CD4+ T cells (p = 0.0108), macrophage (p = 0.0073), and neutrophils (p = 0.0272) as immune cells infiltrating COAD. Conclusion Our study demonstrates the pan-cancer relevance of CDKN2A and revealed a novelty in showing CDKN2A underscores its potential as a diagnostic prognostic biomarker in COAD since CDKN2A is mostly studied at a genetic level across COAD.
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Background Chikungunya virus (CHIKV) infection poses a significant global health threat, necessitating a deeper understanding of its molecular mechanisms for effective management and treatment. This study aimed to understand the molecular and genetic mechanisms of CHIKV infection by analyzing microarray expression data. Methodology National Center for Biotechnology Information (NCBI) GEO2R with an adjusted p-value cut-off of <0.05 and |log2FC ≥ 1.5| was used to identify the differentially expressed genes involved in CHIKV infection using microarray data from the Gene Expression Omnibus (GEO) database, followed by enrichment analysis, protein-protein interaction (PPI) network construction, and, finally, hub gene identification. Results Analysis of the microarray dataset revealed 25 highly significant differentially expressed genes (DEGs), including 21 upregulated and four downregulated genes. PPI network analysis elucidated interactions among these DEGs, with hub genes such as ACTB and CTNNB1 exhibiting central roles. Enrichment analysis identified crucial pathways, including leukocyte transendothelial migration, regulation of actin cytoskeleton, and thyroid hormone signaling, implicating their involvement in CHIKV infection. Furthermore, the study highlights potential therapeutic targets such as ACTB and CTNNB1, which showed significant upregulation in infected cells. Conclusions These findings underscore the complex interplay between viral infection and host cellular processes, shedding light on novel avenues for diagnostic marker discovery and advancing antiviral strategies. In this study, we shed light on the molecular and genetic mechanisms of CHIKV infection and the potential role of ACTB and CTNNB1 genes.
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BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is among the leading causes of chronic morbidity and mortality throughout the world. Potentially, COPD can be prevented by the early detection of COPD, which generally entails spirometry. Physicians in smoking cessation outpatient are in an ideal position to detect early-stage of COPD by the simple examination of the patient. They can also perform spirometry to confirm the diagnosis of COPD. The main objective of this study was to assess the frequency of COPD among smokers in smoking cessation outpatient. Secondary objectives were to Compare two methods for COPD screening, the questionnaire (clinical score) and the mini-electronic spirometer (Neo-6) and to assess the degree of motivation to stop smoking by the announcement of lung age to smokers. METHODS: a prospective cross-sectional study was carried out in four consultations for smoking cessation. Inclusion criteria were male patients aged over 35 years and seen in smoking cessation outpatient. A clinical score was then calculated to detect COPD. This score is based on age, BMI, the quantity of tobacco smoking and the respiratory clinical signs. By establishing this score, we could classify our smokers on consultants with likely COPD if the clinical score>16. Secondly, a measure of the breath with a portable minispirometre "neo6" was performed with quantification of the first second forced expiratory volume (FEV1), forced expiratory volume in 6 seconds (FEV6) and their ratio (FEV1/FEV6). A ratio FEV1/FEV6 less than 0.8 was in favor of an obstructive ventilator defect (DVO). In this case a total body plethysmography was indicated. RESULTS: The sample of the study consisted of 115 male smokers with a mean age of 48±12 years old. A low socio-economic level and a low level of education were found respectively in 50.4% and 58% of smokers. Cigarette smoking is the most consumed form of tobacco. A significant clinical score predicting COPD, was found in 54 patients. The measurement of the breath through the Neo-6 found that 23 (20%) smokers had FEV1/FEV6 less than or equal to 0.7 predicting bronchial obstruction and 26 had a ratio between 0.7 and 0.8. plethysmography confirmed the diagnosis of COPD for 27 patients. So the prevalence of COPD in our sample was of 23.48%. The clinical score had a sensibility of 81.48% and a specificity of 63.64 with a negative predictive value of 91.8%. The sensitivity of the Neo 6 (70.37%) is smaller than the clinical score but the specificity is better than 95.94 % of the clinical score. Its negative predictive value was 91.3%. So when VEMS/VEM6 ratio is greater than 0.7, the probability of COPD remains very low. The announcement of the pulmonary patient age is an important parameter for the motivation to stop smoking. CONCLUSION: The combination of a standardized questionnaire to the measure of breath by Neo6 can further optimize COPD screening.
