Cuproptosis-related gene DLAT serves as a prognostic biomarker for immunotherapy in clear cell renal cell carcinoma: multi-database and experimental verification.

OBJECTIVE: Renal clear cell carcinoma (ccRCC) is the most common type of renal cancer. Here we aim to explore the prognosis and immunotherapeutic value of copper death-related gene Dihydrolipoamide S-acetyltransferase (DLAT) in ccRCC. METHODS: The mRNA and protein expressions and methylation level of DLAT, as well as the relation of DLAT to survival prognosis, clinical characteristics, biological function, and immune microenvironment and responses in patients with ccRCC were evaluated using multiple databases. In addition, 75 paired ccRCC tissue samples and 3 kinds of cell lines were tested for experimental validation. RESULTS: Bioinformatics analysis of multiple databases, qRT-PCR, and western blot verified that DLAT expression in ccRCC was lower than that in paracancerous tissues. Patients with low expression of DLAT had a lower survival rate, worse clinical prognosis, stronger immune cell infiltration and expression of immunosuppressive points, and higher tumor immune dysfunction and exclusion (TIDE) scores. CONCLUSIONS: DLAT was identified as an independent prognostic factor in ccRCC and was closely related to the prognosis and immune responses of patients with ccRCC.

Confirmation of the predictive function of cuproptosis-related gene FDX1 in clear cell renal carcinoma using qRT-PCR and western blotting.

BACKGROUND: Cuproptosis is a novel cell death mechanism, and FDX1 is a key gene associated with cuproptosis. However, it is unclear whether FDX1 has prognostic and immunotherapeutic value for clear cell renal carcinoma (ccRCC). METHODS: Data on FDX1 expression in ccRCC were extracted from various databases and validated using qRT-PCR and western blotting. Moreover, the survival prognosis, clinical features, methylation, and biological functions of FDX1 were evaluated, and the tumor immune dysfunction and exclusion (TIDE) score was used to explore the immunotherapy response to FDX1 in ccRCC. RESULTS: The expression of FDX1 in ccRCC tissues was significantly lower than that in normal tissues, as validated by qRT-PCR and western blotting of patient samples (P < 0.01). Moreover, low FDX1 expression was related to shorter survival time and high immune activation, as indicated by alterations in the tumor mutational burden and tumor microenvironment, stronger immune cell infiltration and immunosuppression point expression, and a higher TIDE score. CONCLUSIONS: FDX1 could serve as a novel and accessible biomarker for predicting survival prognosis, tumor immune landscape, and immune responses in ccRCC.

A signature of six-hypoxia-related genes to evaluate the tumor immune microenvironment and predict prognosis in gastric cancer.

BACKGROUND: Hypoxia will trigger a series of immunosuppressive process in tumor microenvironment, leading to the progression in gastric cancer (GC). This research aims to establish a prognostic model made up of hypoxia-risk-related genes in GC. METHODS: Hypoxic genes were outlined via the protein-protein interaction network. And a prognostic model was developed using univariate cox analysis and lasso regression from data in TCGA. Two independent queues of GEO were used for validation. RESULTS: We set up a hypoxic model presented as an independent prognostic factor for GC. And a nomogram combined this model with clinical features can predict OS with great performance. Furthermore, DNA methylation, IHC and cell line analyses validated the expression of hypoxic genes in GC. CONCLUSIONS: In summary, we proposed and verified a hypoxia-risk-related model, which could reflect the immune microenvironment and predict prognosis in GC.

Using machine learning to find genes associated with sudden death.

Objective: To search for significant biomarkers associated with sudden death (SD). Methods: Differential genes were screened by comparing the whole blood samples from 15 cases of accidental death (AD) and 88 cases of SD. The protein-protein interaction (PPI) network selects core genes that interact most frequently. Machine learning is applied to find characteristic genes related to SD. The CIBERSORT method was used to explore the immune-microenvironment changes. Results: A total of 10 core genes (MYL1, TNNC2, TNNT3, TCAP, TNNC1, TPM2, MYL2, TNNI1, ACTA1, CKM) were obtained and they were mainly related to myocarditis, hypertrophic myocarditis and dilated cardiomyopathy (DCM). Characteristic genes of MYL2 and TNNT3 associated with SD were established by machine learning. There was no significant change in the immune-microenvironment before and after SD. Conclusion: Detecting characteristic genes is helpful to identify patients at high risk of SD and speculate the cause of death.

Potential prognostic biomarkers of sudden cardiac death discovered by machine learning.

OBJECTIVE: Sudden cardiac death (SCD) is a serious public health burden. This study aims to find prognostic biomarkers of SCD using machine learning. METHODS: The myocardial samples from 21 accidental death and 82 sudden death donors were compared to seek for differential genes. Enriched active genes were found according to the PPI interaction network. GSEA analyzed differences in function and pathway between control and experimental groups. Related diseases caused by active genes are mainly exhibited through DO enrichment. Prognostic biomarkers for SCD are identified via two machine learning algorithms. The CIBERSORT method was used to compare the immune microenvironment changes in patients with SCD. RESULTS: SCD was mainly associated with heart and kidney diseases caused by atherosclerosis. DEFA1B, BGN, SERPINE1, CCL2 and HBB are considered to be prognostic biomarkers for SCD after machine learning. And immune infiltration plays an important role in the process of SCD. CONCLUSION: We discovered 5 prognostic biomarkers for SCD. And immune microenvironment changes was also found in SCD. Moreover, atherosclerosis might be an important risk factor for SCD.

Effects on BBPS score with bowel preparation time and dosage.

BACKGROUND: To evaluate the effects on the Boston Bowel Preparation Scale (BBPS) score with different bowel preparation times and dosages. METHODS: Six hundred patients who underwent colonoscopy in the Endoscopy Center of Ningbo No.9 Hospital in 2021 were recruited and randomly assigned to 3 groups: Group A: "4-hour 1 + 2L" bowel preparation regimen; Group B: "6-hour 1 + 2L" bowel preparation regimen; and Group C: "4-hour 0 + 2L" bowel preparation regimen. BBPS score among these groups is compared and analyzed in the Statistical Product and Service Solutions software. RESULTS: There was no difference in baseline characteristics among the three groups of patients (P > .05). There was no significant difference in the BBPS score between Group B and Group C, whereas the BBPS score in Group A was significantly higher than that in Groups B and C (P < .05). CONCLUSION: The "4-hour 1 + 2L" bowel preparation regimen can obtain higher BBPS score for colonoscopy, which is suggested to be the optimal plan for colonoscopy patients of the time and dosage. Definitely, higher BBPS score can improve the quality of colonoscopy diagnosis and treatment consequence.

8DEstablishment and validation of a hypoxia-related signature predicting prognosis in hepatocellular carcinoma.

BACKGROUND: Hypoxia plays a crucial role in immunotherapy of hepatocellular carcinoma (HCC) by changing the tumor microenvironment. Until now the association between hypoxia genes and prognosis of HCC remains obscure. We attempt to construct a hypoxia model to predict the prognosis in HCC. RESULTS: We screened out 3 hypoxia genes (ENO1, UGP2, TPI1) to make the model, which can predict prognosis in HCC. And this model emerges as an independent prognostic factor for HCC. A Nomogram was drawn to evaluate the overall survival in a more accurate way. Furthermore, immune infiltration state and immunosuppressive microenvironment of the tumor were detected in high-risk patients. CONCLUSION: We establish and validate a risk prognostic model developed by 3 hypoxia genes, which could effectively evaluate the prognosis of HCC patients. This prognostic model can be used as a guidance for hypoxia modification in HCC patients undergoing immunotherapy.

A five-lncRNA model predicting overall survival in gastric cancer compared with normal tissues.

AIMS: In cancer research, normal tissues adjacent to the tumor are usually defined as controls to compare with tumor samples, in order to screen out cancer-related genes. Although there is no obvious difference in pathology between normal tissues adjacent to the tumor and healthy tissues, there are significant changes at the molecular level. We aim to explore more potential tumor biomarkers using healthy tissues as controls rather than normal tissues adjacent to the tumor. METHODS: Here we combine the Genotype-Tissue Expression project and The Cancer Genome Atlas for differential gene analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were applied in order to predict the biological effects of related lncRNAs. RESULTS: We established a 5-lncRNA prognosis model with an AUC value of 0.815. Pathway analysis indicated that 5-lncRNA mainly affected tissue carcinogenesis through PI3K-AKT signaling pathway, Focal adhesion, MAPK signaling pathway. CONCLUSION: The 5-lncRNA prognostic model we set up is more conducive to assess the overall survival time of gastric cancer patients.

Molecular Mechanisms of miR-1271 Dysregulation in Human Cancer.

MicroRNA is a small noncoding RNA that plays a role in regulating gene expression. miR-1271 is a tumor suppressor microRNA, which is related to the biological changes of many cancers. miR-1271 is considered a biomarker with a potential prognosis and high therapeutic value in tumors. Besides, the expression of miR-1271 is also regulated by many factors. In this study, we summarize the role of miR-1271 in tumors, focusing on the molecular mechanisms of the target genes of miR-1271. Our review will provide a comprehensive understanding of miR-1271 in tumors, as well as ideas for subsequent tumor research related to miR-1271.

A genomic-clinicopathologic nomogram for predicting overall survival of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common digestive tumor with great heterogeneity and different overall survival (OS) time, causing stern problems for selecting optimal treatment. Here we aim to establish a nomogram to predict the OS in HCC patients. METHODS: International Cancer Genome Consortium (ICGC) database was searched for the target information in our study. Lasso regression, univariate and multivariate cox analysis were applied during the analysis process. And a nomogram integrating model scoring and clinical characteristic was drawn. RESULTS: Six mRNAs were screened out by Lasso regression to make a model for predicting the OS of HCC patients. And this model was proved to be an independent prognostic model predicting OS in HCC patients. The area under the ROC curve (AUC) of this model was 0.803. TCGA database validated the significant value of this 6-mRNA model. Eventually a nomogram including 6-mRNA risk score, gender, age, tumor stage and prior malignancy was set up to predict the OS in HCC patients. CONCLUSIONS: We established an independent prognostic model of predicting OS for 1-3 years in HCC patients, which is available to all populations. And we developed a nomogram on the basis of this model, which could be of great help to precisely individual treatment measures.

Retraction Note: The fatty liver index (FLI) and incident hypertension: a longitudinal study among Chinese population.

An amendment to this paper has been published and can be accessed via the original article.

Association Between RASSF2 Methylation and Gastric Cancer: A PRISMA-Compliant Systematic Review and Meta-Analysis.

RASSF2 is a tumor suppressor gene closely related to gastric cancer. This meta-analysis was designed to assess the quality in the previous studies and establish the value of RASSF2 methylation in the prediction and prognosis of gastric cancer. The eligible literatures with publication deadline of May 3, 2019 were collected from PubMed, EMBASE, CNKI, Wanfang, and CNVIP databases. The correlation between RASSF2 methylation level and gastric cancer was estimated by odds ratio and 95% confidence interval (OR and 95% CI) values. A total of eight articles were included in the study. A total of 517 gastric cancer tissue samples and 517 adjacent nontumor tissue samples were included. The results of the analysis showed that RASSF2 had a significantly higher level of methylation in gastric cancer (OR = 17.56, 95% CI = 7.11-43.35, p-value = 0.009). Meanwhile, we tested whether there was association of RASSF2 methylation with tumor metastasis, and we also analyzed whether there was a gender difference in RASSF2 methylation. However, our results showed no statistical significance of the two aforementioned tests (p > 0.1). Our study suggested that RASSF2 methylation could predict the risk of gastric cancer. However, it might not be feasible for the prediction of tumor metastasis.

Prediction of Overall Survival in Gastric Cancer Using a Nine-lncRNA.

Long noncoding RNA (lncRNA) was closely attached to various cancers according to previous studies. In this study we aimed to investigate an lncRNA signature with prognostic value of over survival (OS) outcomes of gastric cancer (GC). Profiles of mRNAs expression and clinical information of 381 GC tissues and 32 nontumor gastric tissues were downloaded from The Cancer Genome Atlas database. Comparison of various lncRNA expression between cancer tissue and normal tissue was made among these data. In the end, a nine-lncRNA signature was discovered using univariate and multivariate Cox regression analyses, with a prospect possibility of the OS in GC patients. Receiver operating characteristic (ROC) was used to evaluate the accuracy of survival model. The gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were used to predict the possible functions and pathways of these lncRNAs. Altogether 720 distinctively expressed lncRNAs were selected between GC and normal tissues. By univariate and multivariate Cox regression analyses, nine lncRNAs were eventually filtered to set a predictive model, distributing patients into high-risk and low-risk groups with extraordinary different OS. Area under the curve of the ROC curve for the nine-lncRNA signature's prediction of 5-year OS was 0.795. Further functional enrichment analyses indicated that these lncRNAs may be associated with biological processes such as protein binding, DNA replication, and cell cycle. Our study identified a nine-lncRNA signature, which could act as a potential prognostic biomarker in the prediction of GC patients' OS.

The Successful Mechanical Lipectomy Treatment of Cerebral Fat Embolism following Autologous Fat Injection.

Autologous fat injection is becoming a more and more widely accepted procedure in plastic surgery nowadays. Concomitantly, there are many complications. The most serious one is arterial fat embolism, for which there is only poor prognosis and no effective treatment. Here, we report the first case of successful treatment of cerebral fat embolization with the help of mechanical lipectomy. Our patient was found unconscious with left-sided hemiparesis after a facial fat injection surgery 4 hours before. Cerebral artery computed tomography angiography indicated it was multiple fat embolism. Then Solitaire stent (4 × 20 mm) and Solumbra (continuously negative pressure attraction) were utilized for the mechanical extraction of fat emboli. The patient recovered from left-side hemiparesis to muscle strength of Medical Research Council scale grade 4, and National Institutes of Health Stroke Scale score was 0 after 3 months visit. In the cerebral infarction after fat transplantation, mechanical lipectomy can be a novel and significant treatment.

The fatty liver index (FLI) and incident hypertension: a longitudinal study among Chinese population.

BACKGROUND: Hypertension and nonalcoholic fatty liver both have been considered as the serious public health problems in recent years. However, the longitudinal association between hypertension and nonalcoholic fatty liver remains unclear in Chinese population. METHODS: This study was aimed to investigate the longitudinal association between nonalcoholic fatty liver assessed by fatty liver index and the incident hypertension among Chinese population and to evaluate the ability of FLI index, through comparing with the predictive value of other indexes. RESULTS: Four thousand six hundred eighty-six subjects (3177 males and 1509 females) were involved and followed up for 9 years. The subjects were divided into groups according to the fatty liver index. Univariate and multivariate Cox regression models were used to analyze the risk factors of hypertension. After 9 years of follow-up, 2047 subjects developed hypertension. The overall 9-year cumulative incidence of HTN was 43.7%, ranging from 36.0% (FLI <  30) to 75.3% (FLI ≥ 60) (P for trend < 0.001). Cox regression analyses indicated that nonalcoholic fatty liver assessed by fatty liver index was independently and positively associated with the risk of incident hypertension. In receiver operating characteristic (ROC) curve analysis, the ROC curve (AUC) of FLI was 0.701 (95% CI 0.686-0.716), which was larger than that of its components. CONCLUSION: The nonalcoholic fatty liver assessed by FLI independently predicted the incident hypertension among the Chinese population.

Significant association between DRD3 gene body methylation and schizophrenia.

The current study was the first one to reveal the contribution of DRD3 methylation to the risk of different (SCZ) subtypes. This study comprised a total of 30 paranoid (15 males and 15 females) and 29 undifferentiated (15 males and 14 females) SCZ patients and 26 age- and gender-matched controls. Our results showed a significant association of CpG2 with SCZ. A breakdown analysis by gender showed that CpG2 and CpG3 methylation were significantly higher in male patients than male controls, and that CpG5 methylation was significantly higher in female patients than female controls. A further breakdown analysis by both gender and SCZ subtype showed that CpG2 and CpG3 methylation were significantly higher in male paranoid SCZ and male undifferentiated SCZ than male controls. In contrast, CpG2 and CpG3 methylation were significantly lower in female undifferentiated SCZ than female controls. Additionally, CpG5 methylation was significantly higher in female paranoid SCZ than female controls. In conclusion, our findings supported that DRD3 gene body hypermethylation was significantly associated with the risk of SCZ. Future study is needed to clarify the mechanisms by which DRD3 gene body hypermethylation contributes to the risk of SCZ.

Male-specific association between dopamine receptor D4 gene methylation and schizophrenia.

OBJECTIVE: The goal of our study was to investigate whether DRD4 gene DNA methylation played an important role in the susceptibility of Han Chinese SCZ. METHODS: Using the bisulphite pyrosequencing technology, DNA methylation levels of 6 CpG dinucleotides in DRD4 CpG island were measured among 30 paranoid SCZ patients, 30 undifferentiated SCZ patients, and 30 age- and gender-matched healthy controls. RESULTS: Strong correlation was observed among the six CpG sites (r>0.5, P<0.01), thus average methylation levels were applied thereafter. Our results indicated that there was a significant association between DRD4 methylation and the risk of SCZ (P = 0.003), although there was no significant difference in DRD4 methylation between the two SCZ subtypes (P = 0.670). A breakdown analysis by gender showed that the significant association of DRD4 methylation and SCZ was driven by males (P<0.001) but not by females (P = 0.835). DRD4 methylation was significantly associated with p300 in male SCZ patients (r = -0.543, P = 0.005) but not in female SCZ patients (r = 0.110, P = 0.599). Moreover, receiver operating characteristic (ROC) curves showed DRD4 methylation was able to predict the status of SCZ in males [area under curve (AUC) = 0.832, P = 0.002] but not in females (AUC = 0.483, P = 0.876). Finally, a further expression experiment showed that DRD4 methylation in the gene body was positively associated with gene expression, although the exact mechanism of gene regulation remained unknown for this interesting DRD4 methylation. CONCLUSION: The gender disparity in the DRD4 DNA methylation provides novel insights into the pathogenesis of SCZ.