LncRNA BASP1-AS1 interacts with YBX1 to regulate Notch transcription and drives the malignancy of melanoma

Melanoma is a fatal skin malignant tumor with a poor prognosis. We found that long noncoding RNA BASP1-AS1 is essential for the development and prognosis of melanoma. The methylation, RNA sequencing, copy number variation, mutation data, and sample follow-up information of melanoma from The Cancer Genome Atlas (TCGA) were analyzed using weighted gene co-expression network analysis and 366 samples common to the three omics were selected for multigroup clustering analysis. A four-gene prognostic model (BASP1-AS1, LOC100506098, ARHGAP27P1, and LINC01532) was constructed in the TCGA cohort and validated using the GSE65904 series. The expression of BASP1-AS1 was upregulated in melanoma tissues and various melanoma cell lines. Functionally, the ectopic expression of BASP1-AS1 promoted cell proliferation, migration, and invasion in both A375 and SK-MEL-2 cells. Mechanically, BASP1-AS1 interacted with YBX1 and recruited it to the promoter of NOTCH3, initiating its transcription process. The activation of the Notch signaling then resulted in the transcription of multiple oncogenes, including c-MYC, PCNA, and CDK4, which contributed to melanoma progression. Thus, BASP1-AS1 could act as a potential biomarker for cutaneous malignant melanoma

Machine-learning based prediction and analysis of prognostic risk factors in patients with candidemia and bacteraemia: a 5-year analysis

Bacteraemia has attracted great attention owing to its serious outcomes, including deterioration of the primary disease, infection, severe sepsis, overwhelming septic shock or even death. Candidemia, secondary to bacteraemia, is frequently seen in hospitalised patients, especially in those with weak immune systems, and may lead to lethal outcomes and a poor prognosis. Moreover, higher morbidity and mortality associated with candidemia. Owing to the complexity of patient conditions, the occurrence of candidemia is increasing. Candidemia-related studies are relatively challenging. Because candidemia is associated with increasing mortality related to invasive infection of organs, its pathogenesis warrants further investigation. We collected the relevant clinical data of 367 patients with concomitant candidemia and bacteraemia in the first hospital of China Medical University from January 2013 to January 2018. We analysed the available information and attempted to obtain the undisclosed information. Subsequently, we used machine learning to screen for regulators such as prognostic factors related to death. Of the 367 patients, 231 (62.9%) were men, and the median age of all patients was 61 years old (range, 52–71 years), with 133 (36.2%) patients aged >65 years. In addition, 249 patients had hypoproteinaemia, and 169 patients were admitted to the intensive care unit (ICU) during hospitalisation. The most common fungi and bacteria associated with tumour development and Candida infection were Candida parapsilosis and Acinetobacter baumannii, respectively. We used machine learning to screen for death-related prognostic factors in patients with candidemia and bacteraemia mainly based on integrated information. The results showed that serum creatinine level, endotoxic shock, length of stay in ICU, age, leukocyte count, total parenteral nutrition, total bilirubin level, length of stay in the hospital, PCT level and lymphocyte count were identified as the main prognostic factors. These findings will greatly help clinicians treat patients with candidemia and bacteraemia

Comprehensive succinylome analyses reveal that hyperthermia upregulates lysine succinylation of annexin A2 by downregulating sirtuin7 in human keratinocytes

Background and Objectives: Local hyperthermia at 44°C can clear multiple human papillomavirus (HPV)-infected skin lesions (warts) by targeting a single lesion, which is considered as a success of inducing antiviral immunity in the human body. However, approximately 30% of the patients had a lower response to this intervention. To identify novel molecular targets for anti-HPV immunity induction to improve local hyperthermia efficacy, we conducted a lysine succinylome assay in HaCaT cells (subjected to 44°C and 37°C water baths for 30 min). Methods: The succinylome analysis was conducted on HaCaT subjected to 44°C and 37°C water bath for 30 min using antibody affinity enrichment together with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results were validated by western blot (WB), immunoprecipitation (IP), and co-immunoprecipitation (Co-IP). Then, bioinformatic analysis including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, motif characterization, secondary structure, and protein–protein interaction (PPI) was performed. Results: A total of 119 proteins with 197 succinylated sites were upregulated in 44°C-treated HaCaT cells. GO annotation demonstrated that differential proteins were involved in the immune system process and viral transcription. Succinylation was significantly upregulated in annexin A2. We found that hyperthermia upregulated the succinylated level of global proteins in HaCaT cells by downregulating the desuccinylase sirtuin7 (SIRT7), which can interact with annexin A2. Conclusions: Taken together, these data indicated that succinylation of annexin A2 may serve as a new drug target, which could be intervened in combination with local hyperthermia for better treatment of cutaneous warts

Machine‑learning based prediction of prognostic risk factors in patients with invasive candidiasis infection and bacterial bloodstream infection: a singled centered retrospective study

Background Invasive candidal infection combined with bacterial bloodstream infection is one of the common nosocomial infections that is also the main cause of morbidity and mortality. The incidence of invasive Candidal infection with bacterial bloodstream infection is increasing year by year worldwide, but data on China is still limited. Methods We included 246 hospitalised patients who had invasive candidal infection combined with a bacterial bloodstream infection from January 2013 to January 2018; we collected and analysed the relevant epidemiological information and used machine learning methods to find prognostic factors related to death (training set and test set were randomly allocated at a ratio of 7:3). Results Of the 246 patients with invasive candidal infection complicated with a bacterial bloodstream infection, the median age was 63 years (53.25–74), of which 159 (64.6%) were male, 109 (44.3%) were elderly patients (> 65 years), 238 (96.7%) were hospitalised for more than 10 days, 168 (68.3%) were admitted to ICU during hospitalisation, and most patients had records of multiple admissions within 2 years (167/246, 67.9%). The most common blood index was hypoproteinemia (169/246, 68.7%), and the most common inducement was urinary catheter use (210/246, 85.4%). Moreover, the most frequently infected fungi and bacteria were Candida parapsilosis and Acinetobacter baumannii, respectively. The main predictors of death prognosis by machine learning method are serum creatinine level, age, length of stay, stay in ICU during hospitalisation, serum albumin level, C-Reactive protein (CRP), leukocyte count, neutrophil count, Procalcitonin (PCT), and total bilirubin level. Conclusion Our results showed that the most common candida and bacteria infections were caused by Candida parapsilosis and Acinetobacter baumannii, respectively. The main predictors of death prognosis are serum creatinine level, age, length of stay, stay in ICU during hospitalisation, serum albumin level, CRP, leukocyte count, neutrophil count, PCT and total bilirubin level

Development and Validation of a Combined Ferroptosis and Immune Prognostic Model for Melanoma

Background. Melanoma development and progression are significantly influenced by ferroptosis and the immune microenvironment. However, there are no reliable biomarkers for melanoma prognosis prediction based on ferroptosis and immunological response. Methods. Ferroptosis-related genes (FRGs) were retrieved from the FerrDb website. Immune-related genes (IRGs) were collected in the ImmPort dataset. The TCGA (The Cancer Genome Atlas) and GSE65904 datasets both contained prognostic FRGs and IRGs. The model was created using multivariate Cox regression, the least absolute shrinkage and selection operator (LASSO) Cox regression analysis, and the analysis and comparison between the expression patterns of ferroptosis and immune cell infiltration were done. Last but not least, research was conducted to assess the expression and involvement of the genes in the comprehensive index of ferroptosis and immune (CIFI). Results. Two prognostic ferroptosis- and immune-related markers (PDGFRB and FOXM1) were utilized to develop a CIFI. In various datasets and patient subgroups, CIFI exhibits consistent predictive performance. The fact that CIFI is an independent prognostic factor for melanoma patients was revealed. Patients in the CIFI-high group further exhibited immune-suppressive characteristics and had elevated ferroptosis gene expression levels. The results of in vitro research point to the possibility that the PDGFRB and FOXM1 genes function as oncogenes in melanoma. Conclusion. In this study, a novel prognostic classifier for melanoma patients was developed and validated using ferroptosis and immune expression profiles