Background: GIMAP, a GTP enzyme of immune-related proteins, plays a crucial role in immune mechanisms. Investigating GIMAP7 expression in pan-cancer can provide efficient guidance for predicting clinical prognosis and identifying novel immunotherapy targets. Methods: Gene expression in different tumour types and stages was analysed based on The Cancer Genome Atlas and the Genotype-Tissue Expression database. An immunohistochemical assay was used to explore the differences in GIMAP7 protein levels in different tumour types and stages. Further, the cBioPortal was used to obtain the genetic variation characteristics of GIMAP7. Kaplan-Meier analysis and multivariable Cox regression analysis were performed to assess the prognostic value of GIMAP7. The pathways affected by GIMAP7 were studied based on gene set enrichment analysis, and the correlation between GIMAP7 expression and immune infiltration was determined using the TIMER2 database and the CIBERSORT method. ESTIMATE was used to analyse the correlation between GIMAP7 expression and ESTIMATE, immune and stromal scores. In addition, the correlation between GIMAP7 and immunoregulators was analysed. Furthermore, tumour mutational burden and microsatellite instability were evaluated using Spearman correlation assay. Results: GIMAP7 expression was significantly low and predicted better survival status in most tumour types. GIMAP7 was positively correlated with the abundance of CD8 + and CD4 + T cells in the tumour microenvironment. However, the high expression of GIMAP7 was negatively correlated with tumour mutations in uveal melanoma and colon adenocarcinoma. A correlation between GIMAP7 and microsatellite instability was found in rectal adenocarcinoma. Additionally, GIMAP7 presented a robust correlation between immune modulators and immunotherapeutic markers. Moreover, high GIMAP7 expression was significantly related to immune-relevant pathways. Conclusion:This study suggests the potential role of GIMAP7 as a prognostic and immunotherapeutic marker in pan-cancer, laying the groundwork for prospective functional and mechanistic experiments and their impact in the clinical setting.

Recent studies suggest that cuproptosis, a novel mode of cell death, may be associated with the development of cancer. However, no studies are showing its role in tumorigenesis, progression, and prognosis. In the present study, we comprehensively analyzed the expression difference, gene variation and methylation modification of cuproptosis-related genes (CRGs) in pan-cancer. Then, Single sample gene set enrichment analysis (ssGSEA) was used to calculate individual cuproptosis scores (CS). The association of CS with copy number variation, clinical features, immune-related genes, TMB, MSI, and tumor immune dysfunction and exclusion (TIDE) was comprehensively assessed. Single-cell transcriptome sequencing (scRNA-seq) to analyze the activation of cuproptosis in the tumor microenvironment. Immunohistochemistry (IHC) were used to validate the expression of cuproptosis hub-gene. Our study shows that CRGs were significantly expressed in a variety of tumors, and CDKN2A had the highest mutation frequency (49%) in all tumors. A significant increase in the CS was observed in most cancers and were associated with poor prognosis in the majority of tumors. CS was significantly negatively correlated with tumor microenvironment scores in more than 10 tumors and positively correlated with PD-L1 in 11 tumors, suggesting involvement in tumor immune escape. scRNA-seq suggests that CRG scores significantly increased in the cancer cells. This study opens avenues for further research on the role of cuproptosis in the occurrence and development of cancer and the development of targeted therapies based on cuproptosis.

IntroductionThe migrasome is a newly discovered organelle that resembles extracellular vesicles in structure. However, the function of the migrasome in tumors, particularly in relation to tumor immunity and tumor microenvironment, is unclear.MethodsGene expression data, copy number variation raw data, and methylation data of 33 cancer types were downloaded from The Cancer Genome Atlas database. Immunohistochemistry (IHC) based on 114 case of colorectal cancer was used to validate the expression of the migrasome hub-gene. We analyzed the expression, prognosis, genetic variation, and drug sensitivity profiles of migrasome-related genes (MRGs) in pan-cancer datasets. A migrasome score was constructed based on gene set enrichment analysis, and the correlation of migrasomes with the tumor microenvironment was assessed. The CancerSEA was used to perform a single-cell level functional analysis of the migrasome. Additionally, we also analyzed the correlation between migrasomes and tumor mutational burden (TMB), microsatellite instability (MSI), and tumor immune dysfunction and exclusion scores. Single-cell transcriptome sequencing (scRNA-seq) data was used to assess the activation state of migrasomes in the tumor microenvironment.ResultsPIGK expression was significantly up-regulated in 22 of 33 tumors, and high expression of migrasome was estimated to have contributed to poor prognosis. Missense mutations are the most common type of mutation in MRGs. We identified piperlongumine as a potential drug targeting migrasomes. The migrasome score was significantly and positively correlated with the tumor immunity score and the stroma score. In most tumors, the abundance of macrophages in the tumor microenvironment was significantly and positively correlated with the migrasome score. Additionally, the migrasome scores were significantly correlated with the immune checkpoint genes in pan-cancer as well as immune checkpoint therapy-related markers including TMB and MSI. According to scRNA-seq analysis, migrasome differed significantly among cells of the tumor microenvironment. IHC confirmed low expression of ITGA5 and PIGK in colorectal cancer.DiscussionWe performed the first pan-cancer analysis of migrasomes and discovered that they play an important role in tumor development and immune escape. Our study provides new insights into the role of migrasomes in tumor prognosis and immunotherapy.

Objective: The aim of this study was to investigate the clinical characteristics and factors associated with pediatric hypertension and target organ damage (TOD).Methods: We retrospectively reviewed clinical data from 205 children with hypertension treated in our hospital from 2007 to 2018. The patients were classified based on the type of hypertension (primary, secondary) and presence of TOD (heart, brain, retina). Logistic regression analysis was performed to identify the factors independently associated with hypertension and TOD.Results: There were 107 males, 97 females, and one intersex in this study, with an age range of 0.1–17.9 years. Majority of cases (177, 86.3%) had secondary hypertension, while 13.7% had primary hypertension. The most frequent cause of secondary hypertension was renal disease (59.32%). Elevated serum creatinine level (odds ratio [OR] = 7.22, 95% confidence interval [95% CI] = 1.6–32.62, P = 0.01), blood urea nitrogen (OR = 6.33, 95% CI = 1.81–22.19, P = 0.004), serum uric acid level (OR = 3.66, 95% CI = 1.20–11.22, P = 0.023), and albuminuria (OR = 3.72, 95% CI = 1.50–9.26, P = 0.005) were independently associated with secondary hypertension. Elevated serum uric acid and blood urea nitrogen levels were associated with left ventricular hypertrophy (OR = 6.638, 95% CI = 1.349–32.657, P = 0.02) and hypertensive encephalopathy (OR = 4.384, 95% CI = 1.148–16.746, P = 0.031), respectively. Triglyceride level correlated with hypertensive retinopathy (P = 0.001).Conclusion: Pediatric hypertension was most often secondary, with renal disease as the leading cause. Elevated levels of serum uric acid, blood urea nitrogen, serum creatinine, and albuminuria may indicate secondary hypertension in childhood. Elevated serum uric acid, blood urea nitrogen, and triglyceride levels were associated with left ventricular hypertrophy, hypertensive encephalopathy, and hypertensive retinopathy, respectively.