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Computers in Biology and Medicine Sep 2023Gastric carcinoma (GC) is the fourth leading cause of cancer-related mortality worldwide. Patients with advanced GC tend to have poor prognoses and shortened survival....
Identifying mitophagy-related genes as prognostic biomarkers and therapeutic targets of gastric carcinoma by integrated analysis of single-cell and bulk-RNA sequencing data.
Gastric carcinoma (GC) is the fourth leading cause of cancer-related mortality worldwide. Patients with advanced GC tend to have poor prognoses and shortened survival. Finding novel predictive biomarkers for GC prognosis is an urgent need. Mitophagy is the selection degradation of damaged mitochondria to maintain cellular homeostasis, which has been shown to play both pro- and anti-tumor effects. This study combined single-cell sequencing data and transcriptomics to screen mitophagy-related genes (MRGs) associated with GC progression and analyze their clinical values. Reverse transcription-quantitative PCR (RT-qPCR) and immunochemistry (IHC) further verified gene expression profiles. A total of 18 DE-MRGs were identified after taking an intersection of single-cell sequencing data and MRGs. Cells with a higher MRG score were mainly distributed in the epithelial cell cluster. Cell-to-cell communications among epithelial cells with other cell types were significantly upregulated. We established and validated a reliable nomogram model based on DE-MRGs (GABARAPL2 and CDC37) and traditional clinicopathological parameters. GABARAPL2 and CDC37 displayed different immune infiltration states. Given the significant correlation between hub genes and immune checkpoints, targeting MRGs in GC may supplement more benefits to patients who received immunotherapy. In conclusion, GABARAPL2 and CDC37 may be prognostic biomarkers and candidate therapeutic targets of GC.
Topics: Humans; RNA; Mitophagy; Prognosis; Stomach Neoplasms; Sequence Analysis, RNA; Carcinoma
PubMed: 37413850
DOI: 10.1016/j.compbiomed.2023.107227 -
Ugeskrift For Laeger Mar 2024Improved survival after breast cancer treatment comes at a cost in the form of increased risk of late effects. A number of these are summarised in this review. The late... (Review)
Review
Improved survival after breast cancer treatment comes at a cost in the form of increased risk of late effects. A number of these are summarised in this review. The late effects can be divided in 1) late effects after locoregional treatment, e.g., lymphoedema, impaired shoulder movement, and pain; 2) consequences of systemic treatment, e.g. polyneuropathy, problems related to premature menopause, and increased risk of cardio-vascular disease; and 3) general late effects, commonly seen across all cancer types, including fatigue, insomnia, and cognitive impairment. There is a need for more knowledge about risk factors, prognoses, and the most effective treatments.
Topics: Female; Humans; Breast Neoplasms; Treatment Outcome; Sleep Initiation and Maintenance Disorders; Disease Progression; Lymphedema
PubMed: 38533874
DOI: 10.61409/V02230091 -
Frontiers in Immunology 2023Advanced studies have shown a biological correlation between hepatitis B virus (HBV) and B-cell lymphoma, especially diffuse large B-cell lymphoma (DLBCL). Patients with... (Review)
Review
Advanced studies have shown a biological correlation between hepatitis B virus (HBV) and B-cell lymphoma, especially diffuse large B-cell lymphoma (DLBCL). Patients with DLBCL infected with HBV (HBV-associated DLBCL) are clinically characterized by an advanced clinical stage, poor response to front-line immunochemotherapy regimens, and worse clinical prognosis. HBV-associated DLBCL often exhibits abnormal activation of the nuclear factor kappa B pathway as well as mutations in oncogenes, including and . Currently, there is no consensus on any specific and effective treatment for HBV-associated DLBCL. Therefore, in this review, we comprehensively and mechanistically analyzed the natural history of HBV infection and immunity, including HBV-mediated oncogenes, immune escape, epigenetic alterations, dysregulated signaling pathways, and potential therapeutic approaches for HBV-associated DLBCL. We hope that an improved understanding of the biology of HBV-associated DLBCL would lead to the development of novel therapeutic approaches, enhance the number of effective clinical trials, and improve the prognosis of this disease.
Topics: Humans; Hepatitis B virus; Prognosis; Treatment Outcome; Hepatitis B; Lymphoma, Large B-Cell, Diffuse
PubMed: 37483605
DOI: 10.3389/fimmu.2023.1216610 -
The Journal of International Medical... Apr 2024In recent years, radiomics has emerged as a novel research methodology that plays a crucial role in the diagnosis and treatment of ischemic stroke. By integrating... (Review)
Review
In recent years, radiomics has emerged as a novel research methodology that plays a crucial role in the diagnosis and treatment of ischemic stroke. By integrating multimodal medical imaging techniques such as computed tomography and magnetic resonance imaging, radiomics offers in-depth insights into aspects such as the extent of brain tissue damage and hemodynamics. These data help physicians to accurately assess patient condition, select optimal treatment strategies, and predict recovery trajectories and long-term prognoses, thereby enhancing treatment efficacy and reducing the risk of complications. With the anticipated further advancements in radiomic technology, this methodology has great potential for expanded applications in the early detection, treatment, and prognosis of ischemic stroke. The present narrative review explores the burgeoning field of radiomics and its transformative impact on ischemic stroke.
Topics: Humans; Ischemic Stroke; Radiomics; Prognosis; Tomography, X-Ray Computed; Treatment Outcome; Stroke
PubMed: 38565321
DOI: 10.1177/03000605241238141 -
Cancer Medicine Dec 2023The clinicopathologic characteristics and prognosis of nasal and nonnasal extranodal natural killer T-cell lymphoma (ENKTL) are considered to be different. However, the...
BACKGROUND
The clinicopathologic characteristics and prognosis of nasal and nonnasal extranodal natural killer T-cell lymphoma (ENKTL) are considered to be different. However, the underlying features responsible for these differences are not well clarified especially in the era of asparaginase therapy.
METHODS
In total, 1007 newly diagnosed ENKTL patients from 11 medical centers were included in this study. Clinicopathologic characteristics and survival data were collected. The chi-squared test and Kruskal-Wallis test were utilized for the comparison of different groups. Univariable and multivariable Cox proportional hazards models were used to screen prognostic factors.
RESULTS
Overall, 869 (86.3%) patients were nasal forms. Compared to patients with nasal ENKTL, nonnasal patients were at more advanced stages and had poor performance status, bone marrow involvement, elevated serum lactate dehydrogenase (LDH), and CD56-negative status (p < 0.05). The 5-year overall survival (OS) for nasal and nonnasal patients were 65.6% and 45.0%, respectively. The OS of nasal forms patients were superior to nonnasal patients, especially in Eastern Cooperative Oncology Group performance status (ECOG PS) (≥2), advanced stage, KPI (HIR/HR), IPI (HIR/HR), PINK (HR), and high EBV DNA load groups. In patients treated with pegaspargase/L-asparaginase-based regimens, the OS of nasal patients was better than that of nonnasal patients. After adjusting the covariates of age, stage, ECOG PS score, LDH, B symptoms, and BM involvement, results showed that the nonnasal site was associated with poor survival of ENKTL.
CONCLUSIONS
The clinicopathologic characteristics and prognosis of nasal and nonnasal ENKTL patients are different. Nasal forms patients had superior OS than nonnasal patients, especially in the era of asparaginase.
Topics: Humans; Asparaginase; Lymphoma, Extranodal NK-T-Cell; Neoplasm Staging; Prognosis; Retrospective Studies
PubMed: 37902266
DOI: 10.1002/cam4.6674 -
Renal Failure Dec 2023The mortality rate of patients with sepsis-associated acute kidney injury (SA-AKI) in the intensive care unit (ICU) is high, and there is a need for early identification...
The association between lactate dehydrogenase to serum albumin ratio and the 28-day mortality in patients with sepsis-associated acute kidney injury in intensive care: a retrospective cohort study.
BACKGROUND
The mortality rate of patients with sepsis-associated acute kidney injury (SA-AKI) in the intensive care unit (ICU) is high, and there is a need for early identification of SA-AKI patients with poor prognoses. This study investigated the relationship between the lactate dehydrogenase to serum albumin ratio (LAR) and prognosis in patients with SA-AKI.
METHODS
We performed a retrospective cohort study of patients with SA-AKI who are represented in the Medical Information Mart for Intensive Care IV (MIMIC-IV). We used multivariable Cox regression analysis to determine adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analysis, survival curves, and curve fitting were used to evaluate a connection between the LAR and prognosis in patients with SA-AKI.
RESULTS
There were a total of 6453 participants in this research. The average age of the participants was 63.9 ± 16.1 years, and the average LAR was 11.0 (7.6, 17.7)/IU/g. After controlling for variables, the HRs for 28-day mortality were 1.20 (HR: 1.20, 95% CI: 1.05-1.38, ) and 1.61 (HR: 1.61, 95% CI: 1.41-1.84, ) for Tertile 2 (T2, 8.59≤ LAR< 14.66) and Tertile 3 (T3, LAR ≥ 14.66), respectively, compared to Tertile 1 (T1, LAR < 8.59). The outcomes for 90-day mortality and in-hospital death rate were comparable. The Kaplan-Meier (KM) analysis revealed that the group with greater LAR had higher 28-day and 90-day death rates.
CONCLUSION
Our study shows that LAR is associated with poor prognosis in patients with SA-AKI. Higher LAR is associated with higher 28-day, 90-day, and in-hospital mortality.
Topics: Humans; Middle Aged; Aged; Aged, 80 and over; Retrospective Studies; Hospital Mortality; Serum Albumin; L-Lactate Dehydrogenase; Critical Care; Acute Kidney Injury; Intensive Care Units; Prognosis; Sepsis
PubMed: 37194715
DOI: 10.1080/0886022X.2023.2212080 -
BMC Pediatrics Aug 2023IgA vasculitis nephritis (IgAVN) and IgA nephropathy (IgAN) share several clinical and pathological characteristics, though distinctions also exist. Their interrelation,...
BACKGROUND
IgA vasculitis nephritis (IgAVN) and IgA nephropathy (IgAN) share several clinical and pathological characteristics, though distinctions also exist. Their interrelation, however, remains undefined. This study investigates the clinicopathological divergences and prognostic disparities in pediatric patients with IgAVN and IgAN.
METHODS
Our study encompasses 809 pediatric patients with IgAVN and 236 with IgAN, all of whom underwent kidney biopsy. We utilized the Semiquantitative Classification (SQC) scoring system to juxtapose the pathologies of the two conditions, and performed a COX regression analysis to examine factors influencing their prognoses.
RESULTS
Both patient groups demonstrated a predominance of males. A seasonality was observed, with a higher incidence of IgAN in the summer, and IgAVN in the fall (P < 0.0001). Patients with IgAN exhibited more severe tubulointerstitial injury, higher chronicity index, and total biopsy scores compared to those with IgAVN (P < 0.0001). Mesangial deposition intensity of complement C3, and the rate of pure IgA deposition, were found to be greater in patients with IgAVN compared to those with IgAN (P < 0.0001). The intensity of IgA deposition was also significantly higher in IgAVN patients (P = 0.003). IgAVN demonstrated a superior prognosis, with a higher rate of kidney remission (P < 0.0001). COX regression analysis indicated that interstitial fibrosis, as identified in the SQC pathology system, was associated with the prognosis of both conditions. Furthermore, the findings suggest that IgA deposition levels (IgA + + and IgA + + +) could potentially influence the prognosis of IgAVN.
CONCLUSIONS
Compared to IgAVN, IgAN manifests more severely with regard to renal impairment, interstitial damage, and prognosis. The disparities in immune complex deposition levels and locations within the kidneys support the hypothesis of IgAVN and IgAN as distinct diseases. Interstitial fibrosis may serve as a key pathological indicator within the SQC system associated with kidney prognosis in children with IgAVN and IgAN. The degree of IgA deposition could also be linked with the prognosis of IgAVN.
Topics: Male; Humans; Child; Female; Glomerulonephritis, IGA; IgA Vasculitis; Nephritis; Prognosis; Fibrosis; Immunoglobulin A
PubMed: 37620917
DOI: 10.1186/s12887-023-04243-3 -
Scientific Reports Dec 2023Tumor formation is closely associated with disulfidptosis, a new form of cell death induced by disulfide stress-induced. The exact mechanism of action of disulfidptosis... (Randomized Controlled Trial)
Randomized Controlled Trial
Tumor formation is closely associated with disulfidptosis, a new form of cell death induced by disulfide stress-induced. The exact mechanism of action of disulfidptosis in pancreatic cancer (PCa) is not clear. This study analyzed the impact of disulfidptosis-related genes (DRGs) on the prognosis of PCa and identified clusters of DRGs, and based on this, a risk score (RS) signature was developed to assess the impact of RS on the prognosis, immune and chemotherapeutic response of PCa patients. Based on transcriptomic data and clinical information from PCa tissue and normal pancreatic tissue samples obtained from the TCGA and GTEx databases, differentially expressed and differentially surviving DRGs in PCa were identified from among 15 DRGs. Two DRGs clusters were identified by consensus clustering by merging the PCa samples in the GSE183795 dataset. Analysis of DRGs clusters about the PCa tumor microenvironment and differential analysis to obtain differential genes between the two DRG clusters. Patients were then randomized into the training and testing sets, and a prognostic prediction signature associated with disulfidptosis was constructed in the training set. Then all samples were divided into high-disulfidptosis-risk (HDR) and low-disulfidptosis-risk (LDR) subgroups based on the RS calculated from the signature. The predictive efficacy of the signature was assessed by survival analysis, nomograms, correlation analysis of clinicopathological characteristics, and the receiver operating characteristic (ROC) curves. To assess differences between different risk subgroups in immune cell infiltration, expression of immune checkpoint molecules, somatic gene mutations, and effectiveness of immunotherapy and chemotherapy. The GSE57495 dataset was used as external validation, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of DRGs. A total of 12 DRGs with differential expression and prognosis in PCa were identified, based on which a risk-prognosis signature containing five differentially expressed genes (DEGs) was developed. The signature was a good predictor and an independent risk factor. The nomogram and calibration curve shows the signature's excellent clinical applicability. Functional enrichment analysis showed that RS was associated with tumor and immune-related pathways. RS was strongly associated with the tumor microenvironment, and analysis of response to immunotherapy and chemotherapy suggests that the signature can be used to assess the sensitivity of treatments. External validation further demonstrated the model's efficacy in predicting the prognosis of PCa patients, with RT-qPCR and immunohistochemical maps visualizing the expression of each gene in PCa cell lines and the tissue. Our study is the first to apply the subtyping model of disulfidptosis to PCa and construct a signature based on the disulfidptosis subtype, which can provide an accurate assessment of prognosis, immunotherapy, and chemotherapy response in PCa patients, providing new targets and directions for the prognosis and treatment of PCa.
Topics: Humans; Prognosis; Pancreatic Neoplasms; Immunotherapy; Nomograms; Computational Biology; Tumor Microenvironment
PubMed: 38097783
DOI: 10.1038/s41598-023-49752-4 -
Frontiers in Immunology 2023As the most abundant infiltrating immune cells in the tumor microenvironment (TME), tumor-associated macrophages (TAMs) are pivotal in tumor development and treatment....
As the most abundant infiltrating immune cells in the tumor microenvironment (TME), tumor-associated macrophages (TAMs) are pivotal in tumor development and treatment. The present investigation endeavors to explore the potential of M1 macrophage-related genes (MRGs) as biomarkers for assessing risk in individuals with osteosarcoma. RNA-sequence data and clinical data were derived from TCGA and GEO databases. The CIBERSORT method was utilized to discern subtypes of tumor-infiltrating immune cells. Identification of MRGs was achieved through Pearson correlation analysis. A prognostic risk model for MRGs was developed using Cox and LASSO regression analyses. A tripartite gene signature comprising CD37, GABRD, and ARHGAP25 was an independent prognostic indicator and was employed to develop a risk score model. The internal and external validation cohort confirmed the results. The area under the ROC curve (AUC) was determined for survival periods of 1 year, three years, and five years, yielding values of 0.746, 0.839, and 0.850, respectively. The C-index of the risk score was found to be superior to clinicopathological factors. GO/KEGG enrichment showed that the differences between high- and low-risk groups were predominantly associated with immune response pathways. Immune-related analysis related to proportions of immune cells, immune function, and expression levels of immune checkpoint genes all showed differences between the high- and low-risk groups. The qRT-PCR and Western blotting results indicate that CD37 expression was markedly higher in MG63 and U2OS cell lines when compared to normal osteoblast hFOB1.19. In U2OS cell line, GABRD expression levels were significantly upregulated. ARHGAP25 expression levels were elevated in both 143B and U2OS cell lines. In summary, utilizing a macrophage genes signature demonstrates efficacy in predicting both the prognosis and therapy response of OS. Additionally, immune analysis confirms a correlation between the risk score and the tumor microenvironment. Our findings, therefore, provide a cogent account for the disparate prognoses observed among patients and furnish a justification for further inquiry into biomarkers and anti-tumor treatment strategies.
Topics: Humans; Prognosis; Osteosarcoma; Macrophages; Osteoblasts; Bone Neoplasms; Tumor Microenvironment
PubMed: 37465666
DOI: 10.3389/fimmu.2023.1202725 -
Cancer Medicine Sep 2023Human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) is a subtype of breast cancer with a worse prognosis. Little is known about the...
BACKGROUND
Human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) is a subtype of breast cancer with a worse prognosis. Little is known about the relationship between histology and prognosis among different distant metastasis sites (DMS). Our aims were to explore the prognostic value of histologic subtypes in different DMS and screen out specific subtypes with particular DMS that need more attention in HER2+ MBC.
METHODS
HER2+ MBC patient data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2014. Chi-squared tests were utilized to compare histologic subtypes in four DMS. The logistic regression analyses were used to control confounding factors. The log-rank tests were used to analyze the correlation of histologic subtype with disease-specific survival and overall survival. The survival data was analyzed using Kaplan-Meier methods.
RESULTS
A total of 1174 HER2+ MBC patients were involved. First, the distribution of histological subtypes varied across metastatic sites, and the proportions of metastatic sites in different histological subtypes were also different. Furthermore, different histological subtypes within specific DMS showed divergent prognoses, and the different outcomes were shown by distinct DMS for specific histological subtypes. Among them, lobular carcinoma (ILC) subtypes showed the worst prognosis in bone metastasis, and lung metastasis predicted the worst prognosis in infiltration duct and lobular carcinoma (IDC-ILC) subtypes. After further consideration of hormone receptor (HR) status, the IDC-ILC subtype with liver metastasis in HR+/HER2+ MBC patients and the ILC subtype with bone metastasis in HR-/HER2+ MBC patients proved to be noteworthy.
CONCLUSIONS
Histological subtypes are involved in determining the heterogeneity of HER2+ MBC patient prognosis, which is helpful to guide the prognosis prediction and monitoring of HER2+ breast cancer patients in clinics.
Topics: Humans; Female; Breast Neoplasms; Retrospective Studies; Carcinoma, Lobular; Prognosis; Carcinoma, Ductal, Breast; Bone Neoplasms; Receptor, ErbB-2
PubMed: 37605516
DOI: 10.1002/cam4.6469