Differences In Immune Function Research Articles

Single-sample gene set enrichment analysis reveals the clinical implications of immune-related genes in ovarian cancer.

Ovarian cancer (OC) is a common gynecological malignancy with poor prognosis and substantial tumor heterogeneity. Due to the complex tumor immune microenvironment (TIME) among ovarian cancer, only a few patients have an immune response to immunotherapy. To investigate the differences in immune function and identify potential biomarkers in OC, we established a prognostic risk scoring model (PRSM) with differential expression of immune-related genes (IRGs) to identify critical prognostic IRG signatures. Single-sample gene set enrichment analysis (ssGSEA) was used to investigate the infiltration of various immune cells in 372 OC patients. Then, COX regression analysis and Lasso regression analysis were used to screen IRGs and construct PRSM. Next, the immunotherapy sensitivity of different risk groups regarding the immune checkpoint expression and tumor mutation burden was evaluated. Finally, a nomogram was created to guide the clinical evaluation of the patient prognosis. In this study, 320 immune-related genes (IRGs) were identified, 13 of which were selectively incorporated into a Prognostic Risk Scoring Model (PRSM). This model revealed that the patients in the high-risk group were characterized as having poorer prognosis, lower expression of immune checkpoints, and decreased tumor mutation load levels compared with those in the low-risk group. The nomogram based on the risk score can distinguish the risk subtypes and individual prognosis of patients with OC. Additionally, M1 macrophages may be the critical target for immunotherapy in OC patients. With the in-depth analysis of the immune microenvironment of OC, the PRSM was constructed to predict the OC patient prognosis and identify the subgroup of the patients benefiting from immunotherapy.

P53-associated lncRNAs regulate immune functions and RNA-modifiers in gastric cancer

TP53, a guardian of the genome, suppresses or enhances tumors through various regulatory pathways. However, the role of p53-related long non-coding RNAs (lncRNAs) in immune regulation of tumor microenvironment and prognosis of gastric cancer (GC) is so far unelucidated. We analyzed the role of TP53-associated lncRNAs (obtained from the TP53LNC-DB database) in immune regulation, immune cell infiltration and RNA modification in gastric cancer. Firstly, using multivariate COX regression analysis, we identified eight lncRNAs related to the prognosis of GC. Furthermore, based on the expression of the lncRNA signature and risk score, the GC patients were divided into high-risk and low-risk groups. We found that M2-macrophages have significantly higher infiltration in the high-risk group. Similarly, significant differences in immune function (APC_co_stimulation, CCR, and checkpoint) and m6A modification (FTO, ZC3H13, YTHDC1, and RBM15), and m5C modification (NOP2 and TET1) between both groups were also observed. These signature lncRNAs were also positively associated with oxidative stress-related genes (MPO, MAPK14, HMOX1, and APP). Additionally, we found that high expression of GAS5 and low expression of MALAT1 in Helicobacter pylori (H-pylori) positive GC patients. Finally, GC patients in the low-risk group showed higher resistance to immunotherapy while patients in the high-risk group were more sensitive to various chemotherapy drugs. Based on these findings, we conclude that p53-associated lncRNAs signature could potentially predict the immune status and overall survival, and may also be used for risk management and planning immunotherapy for gastric cancer patients.

Establishment of the Diagnostic Signature of Ferroptosis Genes in Multiple Sclerosis.

Ferroptosis is a novel form of membrane-dependent cell death that differs from other cell death modalities such as necrosis, apoptosis, and autophagy. Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system primarily affecting brain and spinal cord neurons. Although the pathogenesis of these two conditions may seem unrelated, recent studies have indicated a connection between ferroptosis and multiple sclerosis. In fact, ferroptosis plays a significant role in the development of MS, as evidenced by the presence of elevated iron levels and iron metabolism abnormalities in the brains, spinal cords, and other neurons of MS patients. These abnormalities disrupt iron homeostasis within cells, leading to the occurrence of ferroptosis. However, there is currently a lack of research on the diagnostic value of ferroptosis-related genes in multiple sclerosis. In this study, we employed bioinformatics methods to identify ferroptosis-related genes (ATM, GSK3B, HMGCR, KLF2, MAPK1, NFE2L1, NRAS, PCBP1, PIK3CA, RPL8, VDAC3) associated with the diagnosis of multiple sclerosis and constructed a diagnostic model. The results demonstrated that the diagnostic model accurately identified the patients' condition. Subsequently, subgroup analysis was performed based on the expression levels of ferroptosis-related genes, dividing patients into high and low expression groups. The results showed differences in immune function and immune cell infiltration between the two groups. Our study not only confirms the correlation between ferroptosis and multiple sclerosis but also demonstrates the diagnostic value of ferroptosis-related genes in the disease. This provides guidance for clinical practice and direction for further mechanistic research.

Comparison of the effects of remimazolam tosylate and propofol on immune function and hemodynamics in patients undergoing laparoscopic partial hepatectomy: a randomized controlled trial

BackgroundLaparoscopic partial hepatectomy inevitably decrease patient immune function. Propofol has been shown to have immunomodulatory effects but is associated with hemodynamic side effects. Despite studies showing a negligible impact of remimazolam tosylate on hemodynamics, it has not been reported for partial hepatectomy patients. Its influence on immune function also remains unexplored. This study sought to investigate the differences in immune function and intraoperative hemodynamics between patients who underwent laparoscopic partial hepatectomy with remimazolam tosylate and those who underwent laparoscopic partial hepatectomy with propofol.MethodsThis was a single-center, randomized controlled trial involving 70 patients, who underwent elective laparoscopic partial hepatectomy. The patients were randomly divided into two groups: the remimazolam group (group R) and the propofol group (group P). In this study, the primary outcomes assessed included the patient’s immune function and hemodynamic parameters, and the secondary outcomes encompassed the patient’s liver function and adverse events.ResultsData from 64 patients (group R, n = 31; group P, n = 33) were analyzed. The differences in the percentages of CD3+, CD4+, CD8+, and NK cells and the CD4+/CD8+ ratio between the two groups were not statistically significant at 1 day or 3 days after surgery. Compared with those in group P, the MAP and HR at T2 and the MAP at T1 in group R were significantly increased(P < 0.05). The differences in HR and MAP at T0, T3, T4, T5, T6, and T7 and HR at T1 between the two groups were not statistically significant. There were no differences in liver function or adverse effects between the two groups, suggesting that remimazolam tosylate is a safe sedative drug(P > 0.05).ConclusionThe effects of remimazolam tosylate on the immune function of patients after partial hepatectomy are comparable to those of propofol. Additionally, its minimal effect on hemodynamics significantly decreases the incidence of hypotension during anesthesia induction, thereby enhancing overall perioperative safety.Trial registrationThe trial was registered on May 9, 2022 in the Chinese Clinical Trial Registry, registration number ChiCTR2200059715 (09/05/2022).

Importance of CD8 Tex cell-associated gene signatures in the prognosis and immunology of osteosarcoma

As a highly aggressive bone malignancy, osteosarcoma poses a significant therapeutic challenge, especially in the setting of metastasis or recurrence. This study aimed to investigate the potential of CD8-Tex cell-associated genes as prognostic biomarkers to reveal the immunogenomic profile of osteosarcoma and guide therapeutic decisions. mRNA expression data and clinical details of osteosarcoma patients were obtained from the TCGA database (TARGET-OS dataset). The GSE21257 dataset (from the GEO database) was used as an external validation set to provide additional information on osteosarcoma specimens. 84 samples from the TARGET-OS dataset were used as the training set, and 53 samples from the GSE21257 dataset served as the external validation cohort. Univariate Cox regression analysis was utilized to identify CD8 Tex cell genes associated with prognosis. The LASSO algorithm was performed for 1000 iterations to select the best subset to form the CD8 Tex cell gene signature (TRS). Final genes were identified using the multivariate Cox regression model of the LASSO algorithm. Risk scores were calculated to categorize patients into high- and low-risk groups, and clinical differences were explored by Kaplan–Meier survival analysis to assess model performance. Prediction maps were constructed to estimate 1-, 3-, and 5 year survival rates for osteosarcoma patients, including risk scores for CD8 Texcell gene markers and clinicopathologic factors. The ssGSEA algorithm was used to assess the differences in immune function between TRS-defined high- and low-risk groups. TME and immune cell infiltration were further assessed using the ESTIMATE and CIBERSORT algorithms. To explore the relationship between immune checkpoint gene expression levels and the two risk-defined groups. A CD8 Tex cell-associated gene signature was extracted from the TISCH database and prognostic markers including two genes were developed. The high-risk group showed lower survival, and model performance was validated by ROC curves and C-index. Predictive plots were constructed to demonstrate survival estimates, combining CD8 Tex cell gene markers and clinical factors. This study provides valuable insights into the molecular and immune characteristics of osteosarcoma and offers potential avenues for advances in therapeutic approaches.

Ex Vivo Immune Function and Modulatory Effects of Calcitriol in Dogs with Naturally Occurring Diabetes Mellitus.

Human patients with type 1 diabetes mellitus (T1DM) are susceptible to several long-term complications that are related to glycemic control and immune dysregulation. Immune function remains relatively unexplored in dogs with naturally occurring diabetes mellitus (NODM). Calcitriol improves various aspects of immune function in a variety of species, but its effect in diabetic dogs remains unexplored. Therefore, the objectives of this study were to (i) evaluate immune function in dogs with NODM and determine if differences exist based on the level of clinical control and (ii) assess the immunomodulatory effects of calcitriol. Twenty diabetic dogs (clinically controlled, n = ten, not controlled, n = ten) and 20 non-diabetic, healthy control dogs were included in this prospective, case-control study. Whole blood was incubated with calcitriol (10-7 M) or negative control, after which the samples were divided for phagocytosis and leukocyte cytokine response experiments. The phagocytosis of opsonized Escherichia coli (E. coli) was evaluated with flow cytometry. The samples for leukocyte cytokine response evaluations were stimulated with lipopolysaccharide (LPS), lipoteichoic acid (LTA), or phosphate buffer solution (PBS; negative control), and tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, and IL-10 were measured in supernatant using a canine-specific multiplex bead-based assay. The leukocytes from diabetic dogs produced higher concentrations of IL-10 (p = 0.01), IL-6 (p < 0.0001), and IL-8 (p < 0.0001) than the control dogs while controlling for the intervention and stimulant. Calcitriol decreased the supernatant concentrations of TNF-α (p < 0.001) and IL-8 (p = 0.04) with concomitant increases in IL-6 (p = 0.005). Diabetic dogs had a lower percentage of leukocytes undergoing phagocytosis (p < 0.0001) but a higher number of bacteria phagocytized per cell (p = 0.001) when compared to the control dogs. Calcitriol had no effect on phagocytic capacity. Lastly, the status of clinical control in diabetic dogs did not yield differences in immune function. These results support that dogs with NODM exhibit immune dysregulation and warrant additional investigation.

Bioinformatic analysis and experimental validation of cuproptosis-related LncRNA as a novel biomarker for prognosis and immunotherapy of oral squamous cell carcinoma

BackgroundThe novel form of regulatory cell death, cuproptosis, is characterized by proteotoxicity, which ultimately leads to cell death. Its targeting has emerged as a promising therapeutic approach for oral squamous cell carcinoma (OSCC). Long noncoding RNAs (lncRNAs) participate in epigenetic regulation and have been linked to the progression, prognosis, and treatment of OSCC. Thus, this study aimed to identify new cuproptosis-related lncRNAs (CRLs), establish predictive models for clinical prognosis, immune response, and drug sensitivity, and provide novel insights into immune escape and tumor drug resistance.MethodsThe present study screened eight CRLs (THAP9-AS1, STARD4-AS1, WDFY3-AS2, LINC00847, CDKN2A-DT, AL132800.1, GCC2-AS1, AC005746.1) using Lasso Cox regression analysis to develop an eight-CRL prognostic model. Patients were categorized into high- and low-risk groups using risk scores. To evaluate the predictive ability of the model, Kaplan-Meier analysis, ROC curves, and nomograms were employed. Furthermore, the study investigated the differences in immune function and anticancer drug sensitivity between the high- and low-risk groups. To validate the expression of CRLs in the model, OSCC cell lines were subjected to quantitative real-time fluorescence PCR (qRT-PCR).ResultsThe results of the study showed that the high-risk group had a shorter overall survival (OS) time in OSCC patients. Cox regression analysis demonstrated that the high-risk score was an independent risk factor for a poor prognosis. The validity of the model was confirmed using ROC curve analysis, and a nomogram was developed to predict the prognosis of OSCC patients. Furthermore, patients in the high-risk group with high TMB had a poorer prognosis. Patients in the low-risk group responded better to immunotherapy than those in the high-risk group. Additionally, the risk scores were significantly associated with drug sensitivity in OSCC patients. Finally, the findings of qRT-PCR supported the reliability of the proposed risk model.ConclusionThe study identified and established the 8-CRL model, which represents a novel pathway of lncRNA regulation of cuproptosis in OSCC. This model provides guidance for the prognosis and treatment of OSCC and offers a new insight into immune escape and tumor drug resistance.

Investigation of sex-based differences in the immunotoxicity of silver nanoparticles

The growing application of silver nanoparticles (AgNPs) in consumer, healthcare, and industrial products has raised concern over potential health implications due to increasing exposure. The evaluation of the immune response to nanomaterials is one of the key criteria to assess their biocompatibility. There are well-recognized sex-based differences in innate and adaptive immune responses. However, there is limited information available using human models. The aim was to investigate the potential sex-based differences in immune functions after exposure to AgNPs using human peripheral blood mononuclear cells (PBMCs) and plasma from healthy donors. These functions include inflammasome activation, cytokine expression, leukocyte proliferation, chemotaxis, plasma coagulation, and complement activation. AgNPs were characterized by dynamic light scattering and transmission electron microscopy. Inflammasome activation by AgNPs was measured after 6- and 24-hours incubations. AgNPs-induced inflammasome activation was significantly higher in the females, especially for the 6-hour exposure. No sex-based differences were observed for Ag ions controls. Younger donors exhibited significantly more inflammasome activation than older donors after 24-hours exposure. IL-10 was significantly suppressed in males and females after exposure. AgNPs suppressed leukocyte proliferation similarly in males and females. No chemoattractant effects, no alterations in plasma coagulation, or activation of the complement were observed after AgNPs exposure. In conclusion, the results highlight that there are distinct sex-based differences in inflammasome activation after exposure to AgNPs in human PBMCs. The results highlight the importance of considering sex-based differences in inflammasome activation induced by exposure to AgNPs in any future biocompatibility assessment for products containing AgNPs.

A novel prognostic model of breast cancer based on cuproptosis-related lncRNAs

ObjectiveBreast cancer (BC) is a deadly form of malignancy responsible for the death of a large number of women every year. Cuproptosis is a newly discovered form of cell death that may have implications for the prognosis of BC. Long non‐coding RNAs (lncRNAs) have been shown to be involved in the progression and development of BC. Here within, a novel model capable of predicting the prognosis of patients with BC was established based on cuproptosis-related lncRNAs.MethodsData of breast cancer patients was downloaded, including clinical information from The Cancer Genome Atlas (TCGA) database and lncRNAs related to cuproptosis were isolated. In total, nine lncRNAs related to copper death were obtained by Cox regression model based on Least Absolute Shrinkage and Selector Operation (LASSO) algorithm for model construction. The model was verified by overall survival (OS), progression-free survival (PFS) and receiver operating characteristic (ROC) curve. The differences in immune function, tumor mutation burden (TMB) and tumor immune dysfunction and exclusion (TIDE) between patients with different risk scores were analyzed.ResultsBased on cuproptosis-related lncRNAs, a prognostic model for predicting BC was constructed. Each patient was assigned a risk score based on our model formula. We found that patients with higher risk scores had significantly lower OS and PFS, increased TMB, and higher sensitivity to immunotherapy.ConclusionsThe model established in this study based on cuproptosis-related lncRNAs may be capable of improving the OS of patients with BC.

Two lncRNA signatures with cuproptosis as a novel prognostic model and clinicopathological value for endometrioid endometrial adenocarcinoma.

Cuproptosis may contribute to tumorigenesis. However, the predictive value and therapeutic significance of cuproptosis-related lncRNAs (CRLs) in endometrioid endometrial adenocarcinoma (EEA) remains unknown. We obtained RNA-seq data from TCGA database and searched the Literature to identify cuproptosis-related genes. Using machine learning models, we identified prognostic lncRNAs for cuproptosis. Immune properties and drug sensitivity were investigated based on these signatures. Further, a ceRNA network was constructed by bioinformatics and in vitro experiments were performed. We determined two cuproptosis-related signatures to build the prognostic model in EEA. Afterward, the risk scores of two cuproptosis-related signatures were associated with clinicopathological molecular typing and as independent prognostic factors for EEA. In addition, we observed significant differences in immune function, checkpoints, and CD8+ T lymphocyte infiltration between the two risk groups. Furthermore, chemotherapy drugs such as AKT inhibitors exhibited lower IC50 values in the high-risk group. We speculate that ACOXL-AS1 can be served as an endogenous 'sponge' to regulate the expression of MTF1 by miR-421. Through in vitro experiments, we preliminarily validated the ceRNA network relationship in the cellular model. In EEAs, this study proposed a broad molecular signature of CRLs are promising biomarkers for predicting clinical outcomes and therapeutic responses.

Male pathology regardless of behaviour drives transmission in an avian host-pathogen system.

Host sex is an important source of heterogeneity in the severity of epidemics. Pinpointing the mechanisms causing this heterogeneity can be difficult because differences in behaviour among sexes (e.g. greater territorial aggression in males) can bias exposure risk, obfuscating the role of immune function, which can lead to differences in pathology, in driving differential susceptibility between sexes. Thus, sex-biased transmission driven by differences in immune function independent of behaviour is poorly understood, especially in non-mammalian systems. Here we examine the previously unexplored potential for male-biased pathology to affect transmission using an avian host-pathogen system. We employ a sex-dependent multistate transmission model parameterized with isolated, individual-based experimental exposures of domestic canaries and experimental transmission data of house finches. The experiment revealed that male birds have shorter incubation periods, longer recovery periods, higher pathogen burdens and greater disease pathology than females. Our model revealed that male-biased pathology led to epidemic size rapidly increasing with the proportion of male birds, with a nearly 10-fold increase in total epidemic size from an all-female to an all-male simulation. Our results demonstrate that female-biased resistance, independent of male behaviour, can drive sex-dependent transmission in wildlife, indicating that sex-based differences in immune function, not just differences in exposure risk, can shape epidemic dynamics.

Unraveling SARS-CoV-2-associated lncRNAs' prognostic significance in lung adenocarcinoma-survival, immunity, and chemotherapy responses

BackgroundThis study investigates the link between SARS-CoV-2-associated long non-coding RNAs (lncRNAs) and lung adenocarcinoma (LUAD). LUAD is a prevalent and aggressive lung cancer type. The study aims to identify prognostic lncRNAs and construct a predictive model while shedding light on potential therapeutic targets during the COVID-19 era. ResultsEight SARS-CoV-2-associated lncRNAs with significant prognostic value in LUAD were identified, forming a robust prognostic risk model. The model exhibited strong predictive performance, with high area under the ROC curve (AUC) values at one, three, and five years. Furthermore, the risk score was an independent prognostic factor, correlating with the cancer stage. Notably, differences in immune function, drug sensitivity, and immune checkpoint expression were observed between high- and low-risk groups. ConclusionsThis study unveils eight SARS-CoV-2-associated lncRNAs as valuable prognostic markers in LUAD, yielding a reliable prognostic risk model. Additionally, the model's ability to predict patient outcomes and its correlation with cancer stage underscores its clinical utility. The observed variances in immune function, drug sensitivity, and immune checkpoint expression suggest potential avenues for personalized LUAD treatment strategies. Clinicians can utilize the prognostic risk model to predict LUAD patient outcomes, informing treatment decisions. The insights into immune function, drug sensitivity, and immune checkpoints offer opportunities for tailored therapies, potentially enhancing patient outcomes. This study underscores the importance of considering the interplay between SARS-CoV-2-associated factors and cancer biology, especially in the context of the COVID-19 pandemic.How to cite: Zhou Q, Yuan T, Xie Z, et al. Unraveling SARS-CoV-2-associated lncRNAs' prognostic significance in lung adenocarcinoma-survival, immunity, and chemotherapy responses. Electron J Biotechnol 2024;67. https://doi.org/10.1016/j.ejbt.2023.10.001.

Comparison of Crude and Wine-Steamed Corni Fructus Based on UPLC-Q-TOF-MS Combined With Pharmacodynamics Screening

Introduction: The dry ripe sarcocarp of Cornus officinalis Sieb.et Zucc (in Chinese Shanyurou) has the properties of tonifying the liver and kidney. Wine-steamed Corni Fructus, as the main processed product from Corni Fructus, is widely used in traditional Chinese clinical medicine. This article aims to study the Corni Fructus composition changes when wine-steamed processed and to discuss the optimal processing technology of Corni Fructus combined with pharmacological experiments. Methods: The differences between Corni Fructus and wine-steamed Corni fructus constituents were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry. The effects of Corni Fructus and wine-steamed Corni Fructus with different processing times were studied from the aspects of immune activity, liver protection, and kidney yin deficiency. Results: A total of 132 compounds were identified in the wine-steamed process of Corni Fructus. There were no significant differences in immune function, liver protection, and kidney yin deficiency of Corni Fructus with different processing times. However, the effects of Corni Fructus processed by wine-steaming were significantly enhanced in all aspects. Conclusion: The wine-steamed Corni Fructus chemical composition may be the material basis for enhancing liver and kidney function. After processing, Corni Fructus can enhance immune function, liver protection function, and liver and kidney toning function.

Construction of a cuproptosis-associated lncRNA prognostic signature for bladder cancer and experimental validation of cuproptosis-related lncRNA UBE2Q1-AS1.

Bladder cancer (BLCA) is the ninth most common malignancy worldwide and the fourth most common cancer in men. Copper levels are significantly altered in patients with thyroid, breast, lung, cervical, ovarian, pancreatic, oral, gastric, bladder, and prostate cancers. Outcomes can be predicted by constructing signatures using lncRNA-related genes associated with outcomes. We identified lncRNAs related to outcomes, those differentially expressed in bladder cancer, and cuproptosis-related lncRNAs from TCGA. We identified the intersection to obtain 12 genes and established a prognostic risk signature consisting of eight genes using LASSO-penalized multivariate Cox analysis. We constructed a training set, performed survival analysis on the high-and low-risk groups, and performed validation in the test and full sets. There existed a substantial contrast in the likelihood of survival among the cohorts of high and low risk. An in-depth analysis of the gene mutations associated with tumors was conducted to evaluate the risk of developing cancer. We also performed gene analysis on neoadjuvant chemotherapy. We conducted experimental validation on the key gene UBE2Q1-AS1 in our prognostic signature. The risk signature we constructed shows significant differences between the high-risk group and the low-risk group. Univariate survival analysis of the eight genes in our signature showed that each gene distinguished between high- and low-risk groups. Sub-group analysis revealed that our risk score differed significantly in tumor stage, age, and gender. The analysis results of the tumor mutation burden (TMB) showed a significant difference in the TMB between the low- and high-risk groups, which had a direct impact on the outcomes. These findings highlight the importance of TMB as a potential prognostic marker in cancer detection and prevention. We analyzed the immune microenvironment and found significant differences in immune function, validation responses, immunotherapy-related positive markers, and critical steps in the tumor immunity cycle between the high- and low-risk groups. We found that the effect of anti-CTLA4 and PD-1 was higher in the high-risk group than in the low-risk group.Gene analysis of neoadjuvant chemotherapy revealed that the treatment effect in the high-risk group was better than in the low-risk group. The key gene UBE2Q1-AS1 in our prognostic signature can significantly influence the cell viability, migration, and proliferation of cancer cells. We established a signature consisting of eight genes constructed from cuproptosis-related lncRNAs that have potential clinical applications for outcomes prediction, diagnosis, and treatment.

The construction of a novel ferroptosis-related lncRNA model to predict prognosis in colorectal cancer patients.

Colorectal cancer (CRC) is the most common gastrointestinal tumor with poor prognosis. Ferroptosis is a pivotal form of programmed iron-dependent cell death different from autophagy and apoptosis, and long noncoding RNA (lncRNA) can influence the prognosis of CRC via regulating ferroptosis. To explore the role and prognostic value of the constructed ferroptosis-related lncRNA model in CRC, a prognostic model was constructed and validated by screening ferroptosis-related lncRNAs associated with prognosis based on the transcriptome data and survival data of CRC patients in The Cancer Genome Atlas database. Regarding the established prognostic models, differences in signaling pathways and immune infiltration, as well as differences in immune function, immune checkpoints, and N6-methyladenosine-related genes were also analyzed. A total of 6 prognostic ferroptosis-related lncRNAs were obtained, including AP003555.1, AC010973.2, LINC01857, AP001469.3, ITGB1-DT and AC129492.1. Univariate independent prognostic analysis, multivariate independent prognostic analysis and receiver operating characteristic curves showed that ferroptosis-related lncRNAs could be recognized as independent prognostic factors. The Kaplan-Meier survival curves and the risk curves showed that the survival time of the high-risk group was shorter. Gene set enrichment analysis enrichment analysis showed that ATP-binding cassette transporters, taste transduction and VEGF signaling pathway were more active in high-risk groups that than in low-risk groups. However, the citrate cycle tricarboxylic acid cycle, fatty acid metabolism and peroxisome were significantly more active in the low-risk group than in the high-risk group. In addition, there were also differences in immune infiltration in the high-low-risk groups based on different methods, including antigen-presenting cell co-stimulation, chemokine receptor, parainflammation, and Type II IFN Response. Further analysis of Immune checkpoints showed that most of the Immune checkpoints such as TNFRSF18, LGALS9 and CTLA4 in the high-risk group were significantly higher than those in the low-risk group, and the expressions of N6-methyladenosine related genes METTL3, YTHDH2 and YTHDC1 were also significantly different in the high-risk group. Ferroptosis-related lncRNAs are closely related to the survival of colorectal cancer patients, which can be used as new biomarkers and potential therapeutic targets for the prognosis of colorectal cancer.

Bioinformatics analysis and experimental validation of cuproptosis-related lncRNA LINC02154 in clear cell renal cell carcinoma

BackgroundClear cell renal cell carcinoma (ccRCC) is common in urinary system tumors. Cuproptosis is a non-apoptotic cell death pathway. Copper binds to fatty acylated mitochondrial proteins and activates various forms of cell death. LncRNA LINC02154 is significantly highly expressed in cells and tissues of many types of tumors, and the risk signature of LINC02154 in some tumors has been validated for effectiveness.MethodsWe constructed a risk prognostic signature by obtaining differentially expressed long noncoding RNAs (lncRNAs) associated with ccRCC outcomes and cuproptosis from The Cancer Genome Atlas (TCGA). We used TCGA to construct training and testing sets to analyze the risk signature and the impact of LINC02154, and we performed relevant survival analyses. Tumor mutational burdens were analyzed in different LINC02154 expression groups and risk score groups. We next analyzed the immune microenvironment of LINC20154. We performed LINC20154-related drug sensitivity analyses. We also investigated the cellular function of LINC02154 in the ACHN cell line and performed CCK-8 assay, EdU, wound-healing assay, and Transwell assay. The essential genes FDX1 and DLST of cuproptosis were detected by western blot.ResultsWe demonstrated that LINC02154’s impact on outcomes was statistically significant. We also demonstrated the association of different ages, genders, stages, and grades with LINC02154 and risk models. The results showed a significant difference in tumor mutation burden between the groups, which was closely related to clinical prognosis. We found differences in immune cells among groups with different levels of LINC02154 expression and significant differences in immune function, immunotherapeutic positive markers, and critical steps of the immune cycle. The sensitivity analysis showed that differential expression of LINC02154 discriminated between sensitivity to axitinib, doxorubicin, gemcitabine, pazopanib, sorafenib, sunitinib, and temsirolimus. This difference was also present in the high-risk group and low-risk group. We demonstrated that the proliferation and migration of t ACHN cells in the LINC02154 knockdown group were inhibited. The western blot results showed that the knockdown of LINC02154 significantly affected the expression of FDX1 and DLST, critical genes of cuproptosis.ConclusionFinally, we demonstrated that LINC02154 and our constructed risk signature could predict outcomes and have potential clinical value.

Splicing factor-mediated regulation patterns reveals biological characteristics and aid in predicting prognosis in acute myeloid leukemia

BackgroundAlternative splicing (AS) of RNA is a fundamental biological process that shapes protein diversity. Many non-characteristic AS events are involved in the onset and development of acute myeloid leukemia (AML). Abnormal alterations in splicing factors (SFs), which regulate the onset of AS events, affect the process of splicing regulation. Hence, it is important to explore the relationship between SFs and the clinical features and biological processes of patients with AML.MethodsThis study focused on SFs of the classical heterogeneous nuclear ribonucleoprotein (hnRNP) family and arginine and serine/arginine-rich (SR) splicing factor family. We explored the relationship between the regulation patterns associated with the expression of SFs and clinicopathological factors and biological behaviors of AML based on a multi-omics approach. The biological functions of SRSF10 in AML were further analyzed using clinical samples and in vitro experiments.ResultsMost SFs were upregulated in AML samples and were associated with poor prognosis. The four splicing regulation patterns were characterized by differences in immune function, tumor mutation, signaling pathway activity, prognosis, and predicted response to chemotherapy and immunotherapy. A risk score model was constructed and validated as an independent prognostic factor for AML. Overall survival was significantly shorter in the high-risk score group. In addition, we confirmed that SRSF10 expression was significantly up-regulated in clinical samples of AML, and knockdown of SRSF10 inhibited the proliferation of AML cells and promoted apoptosis and G1 phase arrest during the cell cycle.ConclusionThe analysis of splicing regulation patterns can help us better understand the differences in the tumor microenvironment of patients with AML and guide clinical decision-making and prognosis prediction. SRSF10 can be a potential therapeutic target and biomarker for AML.

Characteristics of m6A-related LncRNAs in breast cancer as prognostic biomarkers and immunotherapy.

N6-methyladenosine (m6A) is a common RNA modification in coding and non-coding RNAs and plays an important role in the occurrence and development of breast cancer (BC). However, the role of m6A-related lncRNAs in breast cancer prognosis is unclear. This study aimed to help verify the biological function of m6A-related lncRNAs in breast cancer prognosis through bio-informatics techniques. First, we screened 18 m6A-related lncRNAs from the TCGA database: AL137847.1, AC137932.2, OTUD6B-AS1, MORF4L2-AS1, AC078846.1, AC012442.1, AL118556.1, AL138955.1, AC009754.1, AC024257.4, AL391095.1, AC024270.3, AC087392.1, LINC02649, AC090948.2, AL158212.1, ITGA6-AS1, AL133243.2 and constructed a risk-prognosis model based on this. Based on the model's median risk score, BC patients were divided into high-risk and low-risk groups. Then, the predictive value of the model was verified by Cox regression, Lasso regression, Kaplan-Meier curve and ROC curve analysis, and biological differences between the two groups were verified by GO enrichment analysis, tumor mutation burden, immune indications and in vitro tests. Importantly, the risk score of this prognostic model is an excellent independent prognostic factor, and m6A regulators are differentially expressed in patients with different risks. In addition, based on patients' different sensitivities to drugs, some drug candidates for different risk populations are screened to provide targets for breast cancer treatment. The difference in immune function between high-risk and low-risk patients also affected the sensitivity to immunotherapy. In the validation of clinical samples, we analyzed the expression of relevant lncRNAs in different risk groups and speculated the possible impact on the prognosis of breast cancer patients. The risk assessment tool built based on the full analysis of these m6A-related genes and m6A-related lncRNA libraries, as well as the m6A-related lncRNAs, has a high prognostic prediction ability, which may provide a supplementary screening method for accurately judging the prognosis of BC and a new perspective for personalized treatment of breast cancer patients.

Efficacy and safety of HIFU in combination with TACE in unresectable pediatric HB: A randomized, controlled, single-center clinical trial

Hepatoblastoma (HB) is the most common liver tumor in children, and the main treatment for HB is currently surgery. Studies have shown that transcatheter arterial chemoembolization (TACE) combined with high intensity focused ultrasound (HIFU) has significant efficacy, but there are relatively few studies on TACE combined with HIFU in China. To investigate the effect of using HIFU combined with TACE on patients' liver function impairment and immune function in pediatric HB patients and to analyze the effectiveness and safety. The clinical data of 110 unresectable pediatric HB patients treated in our hospital from December 2019 to December 2021 were selected as the subjects and divided into 2 groups. The comparison group was treated with TACE, and the combination group was treated with HIFU on the basis of the comparison group. The differences in immune function, survival, treatment side effects and clinical efficacy between the 2 groups were observed. In the combined group, the 1-year survival rate was 100%, the 3-year survival rate was 84.0%, the 5-year survival rate was 16.0%; while in comparison group, it was 82%, 16%, 0%, respectively. The ratio of CD4+/CD8+ in the combined group were significantly higher than in the comparison group after treatment (P < .05). Granulocytopenia, mucositis, thrombocytopenia, and cardiac and renal toxicity were significantly lower in the combined group than in the comparison group, and the effective rate of the combined group was 98.00% which was significantly higher than that of the control group (76.00%) (P < .05). Comparative study of HB in children treated with HIFU combined with TACE is more effective, effectively improving the immune level of patients, significantly increasing the remission rate, which can improve the tumor necrosis and improve the survival quality of patients, and is a better choice for HB in children.

Cuproptosis-Related LncRNA Signature for Predicting Prognosis of Hepatocellular Carcinoma: A Comprehensive Analysis.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and has a poor prognosis. Cuproptosis is a novel mode of cell death that has only recently been discovered. Considering the critical role of lncRNAs in liver cancer development, the aim of this study was to construct a prognostic signature based on cuproptosis-related lncRNAs (CRlncRNAs). We downloaded RNA-sequencing data and corresponding clinical information of patients with HCC from The Cancer Genome Atlas (TCGA) database. To verify the robustness of the model, we added an external validation set obtained from the Gene Expression Omnibus (GEO): GSE40144. In addition, we identified the cuproptosis-related genes (CRGs) based on previous reports. Pearson correlation analysis, univariate Cox regression, and least absolute shrinkage and selection operator (LASSO) Cox regression analysis were utilized to screen for genes associated with prognosis. On this basis, multivariate Cox regression and stepAIC were used to further construct and optimize the prognostic model. The simplified signature with the lowest Akaike information criterion (AIC) value was considered the prognostic signature. Seven different algorithms were used to perform immune infiltration analysis. The single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm was utilized to find the difference in immune function between the high- and low-risk groups. Finally, in vitro experiments were performed by quantitative real-time PCR (qRT-PCR) analysis using HCC cell lines to validate the expression of prognostic genes. We identified 3 lncRNAs (CYTOR, LINC00205, and LINC01184) as independent risk factors for HCC. The receiver operating characteristic (ROC) curves calculated that the AUC at 1, 3, and 5 years reached 0.717, 0.633, and 0.607, respectively. The expression levels of 41 immune checkpoints differed significantly between the high- and low-risk groups, and there were significant differences in sensitivity to immunotherapy between the high- and low-risk groups. The risk model could also serve as a promising predictor of immunotherapeutic response, which has been verified by the TIDE algorithm (p < 0.001). Overall, we propose a signature related to CRlncRNAs that can be used to predict the prognosis of HCC patients, which was validated in external cohort and in vitro experiments.