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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 -
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 -
Hepatology International Apr 2024
Topics: Humans; Nomograms; Prognosis
PubMed: 38424395
DOI: 10.1007/s12072-023-10612-y -
Cancer Journal (Sudbury, Mass.)Uveal melanoma (UM), arising from intraocular melanocytes, poses a complex clinical challenge with a substantial risk of distant metastasis, often to the liver.... (Review)
Review
Uveal melanoma (UM), arising from intraocular melanocytes, poses a complex clinical challenge with a substantial risk of distant metastasis, often to the liver. Molecular profiling, encompassing genetic, cytogenetic, gene expression, and immunological subsets, plays a pivotal role in determining prognoses. The evolving landscape includes promising systemic treatments, such as tebentafusp, a novel immune-modulating bispecific fusion protein, and targeted therapies. Combined regional and systemic approaches, including immune checkpoint inhibitors and innovative liver-directed therapy, are also under investigation. Although recent progress has improved outcomes, ongoing research aims to address the unique challenges of UM and develop effective therapies, particularly for HLA-A*02:01-negative patients who represent a significant unmet medical need. This review comprehensively discusses the molecular characteristics of UM, risk stratification methods, and the current and future spectrum of regional and systemic therapeutic modalities.
Topics: Humans; Melanoma; Uveal Neoplasms; Prognosis
PubMed: 38527262
DOI: 10.1097/PPO.0000000000000708 -
Cancer Treatment Reviews Nov 2023Gastric cancer (GC) is a highly aggressive malignancy that remains a significant contributor to cancer-related mortality worldwide, despite a decline in incidence in... (Review)
Review
Gastric cancer (GC) is a highly aggressive malignancy that remains a significant contributor to cancer-related mortality worldwide, despite a decline in incidence in recent years. Early-stage GC poses a diagnostic challenge due to its asymptomatic nature, leading to poor prognoses for most patients. Conventional treatment approaches, including chemotherapy and surgery, have shown limited efficacy in improving outcomes for GC patients. The advent of immune checkpoint inhibitors (ICIs) has revolutionized cancer therapy, yielding durable responses across various malignancies. However, the clinical benefits of ICIs in GC have been modest, underscoring the need for a comprehensive understanding of immune cell functions within the GC tumor microenvironment (TME). Regulatory T cells (Tregs), a subset of T lymphocytes, play a pivotal role in GC development and progression and serve as prognostic biomarkers for GC patients. This review aims to elucidate the multifaceted roles of Tregs in the pathogenesis, progression, and prognosis of gastric cancer, and establish their actual and future potential as therapeutic targets. By providing insights into the intricate interplay between Tregs and the TME, this review strives to stimulate further investigation and facilitate the development of targeted Treg-based therapeutic strategies for GC.
Topics: Humans; Stomach Neoplasms; T-Lymphocytes, Regulatory; Prognosis; Tumor Microenvironment; Immune Checkpoint Inhibitors
PubMed: 37769435
DOI: 10.1016/j.ctrv.2023.102629 -
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 -
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 -
Aging Oct 2023The purpose of the study was to investigate the role of exosome and lipid metabolism-related genes (EALMRGs) mRNA levels in the diagnosis and prognosis of Pancreatic...
OBJECTIVE
The purpose of the study was to investigate the role of exosome and lipid metabolism-related genes (EALMRGs) mRNA levels in the diagnosis and prognosis of Pancreatic Adenocarcinoma (PAAD).
METHODS
The mRNA expression pattern of PAAD and pan-cancers with prognostic data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. EALMRGs were acquired from GeneCards and MSigDB database after merging and deduplication. Prognostic EALMRGs were screened through univariate COX regression analysis, and a prognostic model was constructed based on these genes by least absolute shrinkage and selection operator (LASSO) regression. The prognostic value of EALMRGs was then validated in pan-cancer data. The time characteristics ROC curve analysis was performed to evaluate the effectiveness of the prognostic genes.
RESULTS
We identified 5 hub genes (ABCB1, CAP1, EGFR, PPARG, SNCA) according to high and low-risk groups of prognoses. The risk formula was verified in three other cohort of pancreatic cancer patients and was explored in pan-cancer data. Additionally, T cell and dendritic cell infiltration was significantly increased in low-risk group. The expression of the 5 hub genes was also identified in single-cell sequencing data of pancreatic cancer with pivotal pathways. Additionally, functional enrichment analysis based on pancreatic cancer data in pancreatic cancer showed that protein serine/threonine kinase activity, focal adhesion, actin binding, cell-substrate junction, organic acid transport, and regulation of transporter activity were significant related to the expression of genes in EALMRGs.
CONCLUSIONS
Our risk formula shows potential prognostic value in multiple cancers and manifest pivotal alterations in immune infiltration and biological pathway in pancreatic cancer.
Topics: Humans; Adenocarcinoma; Pancreatic Neoplasms; Lipid Metabolism; Exosomes; Prognosis; RNA, Messenger
PubMed: 37857015
DOI: 10.18632/aging.205130 -
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