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Frontiers in Bioscience (Landmark... Aug 2023Breast cancer is the commonest global malignancy and the primary cause of carcinoma death. MCM6 is vital to carcinogenesis, but the pathogenesis of MCM6 remains unclear.
BACKGROUND
Breast cancer is the commonest global malignancy and the primary cause of carcinoma death. MCM6 is vital to carcinogenesis, but the pathogenesis of MCM6 remains unclear.
METHODS
MCM6 expression in patients with breast cancer was examined through The Cancer Genome Atlas (TCGA) database, immunohistochemistry, Quantitative Real-Time PCR (qRT‒PCR) and Western blotting. The prognostic factors were assessed by the Kaplan‒Meier method and Cox regression. On the basis of the key factors selected by multivariable Cox regression analysis, a nomogram risk prediction model was adopted for clinical risk assessment. The TCGA database was utilized to determine how MCM6 is correlated with chemotherapy sensitivity, immune checkpoint-related genes (ICGs), tumor-infiltrating immune cells, along with tumor mutation burden (TMB) and methylation. The impact of MCM6 on carcinoma cells was investigated in terms of proliferation, cell cycle as well as migrating and invasive behavior through CCK assays, flow cytometry, wound healing assays, Transwell assays and xenotransplantation experiments.
RESULTS
MCM6 expression was upregulated, which is closely associated with the size of the tumor ( = 0.001) and lymph node metastasis ( = 0.012) in patients with breast cancer. Multivariate analysis revealed MCM6 to be an independent risk factor for prognosis in patients with breast carcinoma. The nomograph prediction model included MCM6, age, ER, M and N stage, which displayed good discrimination with a C index of 0.817 and good calibration. Overexpression of MCM6 correlated with chemotherapy sensitivity, immune checkpoint-related genes (ICGs), tumor-infiltrating immune cells, tumor mutation burden (TMB), and methylation. Silencing MCM6 significantly inhibited proliferation, prolonged the G1 phase of the cell cycle, and restrained the proliferation, migration and invasive behavior of cancerous cells and inhibited tumor growth .
CONCLUSIONS
Our research shows that MCM6 is highly expressed in breast cancer and can be used as an independent prognostic factor, which is expected to become a new target for the treatment of breast cancer in the future.
Topics: Humans; Female; Breast Neoplasms; Prognosis; Cell Cycle; Biomarkers; Carcinoma; Minichromosome Maintenance Complex Component 6
PubMed: 37664925
DOI: 10.31083/j.fbl2808188 -
Autoimmunity Dec 2023Constituted by various heterogeneous cells, the tumor microenvironment (TME) is capable of promoting tumor proliferation, invasion, and metastasis through extensive...
Constituted by various heterogeneous cells, the tumor microenvironment (TME) is capable of promoting tumor proliferation, invasion, and metastasis through extensive crosstalk. The pivotal factor influencing the survival time of patients and their response to immunotherapy lies in the intratumoral immune environment. We obtained 112 differential genes related to T cell-mediated tumor killing in LUAD by employing bioinformatics analysis on the basis of the TCGA and TISIDB databases. Then the 6-gene prognostic risk score model (, , , , , and ) was constructed by conducting univariate LASSO as well as multivariate Cox regression analyses. The median risk score was taken as the threshold to classify the samples into two groups. Survival analysis revealed that the low-risk group exhibited a more favorable prognosis. Subsequently, the Cox regression analysis combined with clinical information (age, gender, and pathological stage) and the risk score of LUAD patients demonstrated the potential of this model as an independent prognostic factor. The nomogram established based on clinical information and a risk score in combination with the calibration curve indicated that this model had good predictive ability. Notable enrichment of the differential genes from the high- and low-risk groups was discovered in immune-associated processes or pathways, as shown by the GO and KEGG enrichment analyses. The combined use of single-sample gene enrichment analysis (ssGSEA) and immunophenoscore (IPS) demonstrated heightened immune infiltration and IPS scores in the low-risk group, indicating that immunotherapy was likely to show good efficacy in patients from this group. To sum up, the prognostic model of LUAD constructed based on T-cell-mediated cell killing-related genes was not only capable of screening the prognosis of LUAD patients but was also used for screening those LUAD patients with high sensitivity to immunotherapy. Our study offered novel insights into the clinical treatment and prognostic prediction of LUAD patients.
Topics: Humans; Prognosis; T-Lymphocytes; Adenocarcinoma of Lung; Apoptosis; Lung Neoplasms; Tumor Microenvironment
PubMed: 37624966
DOI: 10.1080/08916934.2023.2250097 -
Genomics Nov 2023Big data mining and experiments are widely used to mine new prognostic markers.
BACKGROUND
Big data mining and experiments are widely used to mine new prognostic markers.
METHODS
Candidate genes were identified from CROEMINE and FerrDb. Kaplan-Meier survival and Cox regression analysis were applied to assess the association of genes with Overall survival time (OS) and Disease-free survival time (DFS) in two HCC cohorts. Real-time quantitative polymerase chain reaction (RT-qPCR) and Immunohistochemistry were performed in HCC samples.
RESULTS
21 and 15 genes that can predict OS and DFS, which had not been reported before, were identified from 719 genes, respectively. Survival analysis showed elevated mRNA expression of GLMP, SLC38A6, and WDR76 were associated with poor prognosis, and three genes combination signature was an independent prognostic factor in HCC. RT-qPCR and Immunohistochemistry confirmed the results.
CONCLUSIONS
We established a novel computational process, which identified the expression levels of GLMP, SLC38A6, and WDR76 as potential ferroptosis-related biomarkers indicating the prognosis of HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Ferroptosis; Biomarkers, Tumor; Kaplan-Meier Estimate; Prognosis; DNA-Binding Proteins; Cell Cycle Proteins
PubMed: 37866659
DOI: 10.1016/j.ygeno.2023.110733 -
BMC Cancer Nov 2023Accumulating evidence indicates that type II cystatin (CST) genes play a pivotal role in several tumor pathological processes, thereby affecting all stages of...
BACKGROUND
Accumulating evidence indicates that type II cystatin (CST) genes play a pivotal role in several tumor pathological processes, thereby affecting all stages of tumorigenesis and tumor development. However, the prognostic and predictive value of type II CST genes in GC has not yet been investigated.
METHODS
The present study evaluated the expression and prognostic value of type II CST genes in GC by using The Cancer Genome Atlas (TCGA) database and the Kaplan-Meier plotter (KM plotter) online database. The type II CST genes related to the prognosis of GC were then screened out. We then validated the expression and prognostic value of these genes by immunohistochemistry. We also used Database for Annotation, Visualization, and Integrated Discovery (DAVID), Gene Multiple Association Network Integration Algorithm (GeneMANIA), Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), nomogram, genome-wide co-expression analysis, and other bioinformatics tools to analyze the value of type II CST genes in GC and the underlying mechanism.
RESULTS
The data from the TCGA database and the KM plotter online database showed that high expression of CST2 and CST4 was associated with the overall survival (OS) of patients with GC. The immunohistochemical expression analysis showed that patients with high expression of CST4 in GC tissues have a shorter OS than those with low expression of CST4 (HR = 1.85,95%CI: 1.13-3.03, P = 0.015). Multivariate Cox regression analysis confirmed that the high expression level of CST4 was an independent prognostic risk factor for OS.
CONCLUSIONS
Our findings suggest that CST4 could serve as a tumor marker that affects the prognosis of GC and could be considered as a potential therapeutic target for GC.
Topics: Humans; Prognosis; Stomach Neoplasms; Gene Regulatory Networks; Nomograms; Cystatins
PubMed: 37978366
DOI: 10.1186/s12885-023-11550-6 -
Cancer Immunology, Immunotherapy : CII Dec 2023Increasing evidence suggests that mucosal-associated invariant T cells (MAITs) play a crucial role in anti-tumor responses against various cancers. In this study, we...
Increasing evidence suggests that mucosal-associated invariant T cells (MAITs) play a crucial role in anti-tumor responses against various cancers. In this study, we investigated the immune characteristics of MAIT cells in patients with acute myeloid leukemia (AML). Using multi-parameter flow cytometry, we performed phenotypic and functional analysis of MAITs in peripheral blood or bone marrow samples collected from 131 patients with AML including 99 newly diagnosed, 18 remission, and 14 relapsed cases, as well as 69 healthy controls. We found that MAITs exhibit signs of aging and exhaustion, particularly in CD8 MAITs subset, at newly diagnosis. MAITs exhibit an effector memory or terminally differentiated phenotype. Frequency and number of MAITs reflect AML cell genetic features, tumor burden, disease status, and treatment responsiveness. Moreover, MAITs exhibit a highly activated or even exhausted state, as indicated by upregulation of PD-1. Furthermore, impaired production of Th1-type cytokines and increased secretion of Th17-type cytokines, granzyme B, and perforin were observed in MAITs from AML patients. Additionally, MAITs shifted toward producing cytokines that promote tumor progression, such as IL-8. Lower frequency of MAITs was associated with poorer overall survival (OS), and multivariate analysis revealed that MAITs frequency < 2.12% was an independent prognostic factor affecting OS. Collectively, our findings suggest that MAITs may play a role in immune deficiency in AML, emphasizing their potential importance in AML pathogenesis and treatment. These discoveries provide a theoretical basis for the development of novel immunotherapeutic strategies in AML.
Topics: Humans; Mucosal-Associated Invariant T Cells; Prognosis; Leukemia, Myeloid, Acute; Cytokines; Th17 Cells
PubMed: 37932426
DOI: 10.1007/s00262-023-03574-5 -
Frontiers in Immunology 2023Lipid metabolic reprogramming is gaining attention as a hallmark of cancers. Recent mounting evidence indicates that the malignant behavior of breast cancer (BC) is...
INTRODUCTION
Lipid metabolic reprogramming is gaining attention as a hallmark of cancers. Recent mounting evidence indicates that the malignant behavior of breast cancer (BC) is closely related to lipid metabolism. Here, we focus on the estrogen receptor-positive (ER+) subtype, the most common subgroup of BC, to explore immunometabolism landscapes and prognostic significance according to lipid metabolism-related genes (LMRGs).
METHODS
Samples from The Cancer Genome Atlas (TCGA) database were used as training cohort, and samples from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), Gene Expression Omnibus (GEO) datasets and our cohort were applied for external validation. The survival-related LMRG molecular pattern and signature were constructed by unsupervised consensus clustering and least absolute shrinkage and selection operator (LASSO) analysis. A lipid metabolism-related clinicopathologic nomogram was established. Gene enrichment and pathway analysis were performed to explore the underlying mechanism. Immune landscapes, immunotherapy and chemotherapy response were further explored. Moreover, the relationship between gene expression and clinicopathological features was assessed by immunohistochemistry.
RESULTS
Two LMRG molecular patterns were identified and associated with distinct prognoses and immune cell infiltration. Next, a prognostic signature based on nine survival-related LMRGs was established and validated. The signature was confirmed to be an independent prognostic factor and an optimal nomogram incorporating age and T stage (AUC of 5-year overall survival: 0.778). Pathway enrichment analysis revealed differences in immune activities, lipid biosynthesis and drug metabolism by comparing groups with low- and high-risk scores. Further exploration verified different immune microenvironment profiles, immune checkpoint expression, and sensitivity to immunotherapy and chemotherapy between the two groups. Finally, arachidonate 15-lipoxygenase (ALOX15) was selected as the most prominent differentially expressed gene between the two groups. Its expression was positively related to larger tumor size, more advanced tumor stage and vascular invasion in our cohort (n = 149).
DISCUSSION
This is the first lipid metabolism-based signature with value for prognosis prediction and immunotherapy or chemotherapy guidance for ER+ BC.
Topics: Humans; Female; Breast Neoplasms; Lipid Metabolism; Prognosis; Nomograms; Lipids; Tumor Microenvironment
PubMed: 37469520
DOI: 10.3389/fimmu.2023.1199465 -
Gastric Cancer : Official Journal of... Jul 2023Body weight loss (BWL) is a negative prognostic factor in metastatic gastric or gastroesophageal junction cancer (mGC/GEJC). In the phase III TAGS study,... (Randomized Controlled Trial)
Randomized Controlled Trial
Body weight loss as a prognostic and predictive factor in previously treated patients with metastatic gastric cancer: post hoc analyses of the randomized phase III TAGS trial.
BACKGROUND
Body weight loss (BWL) is a negative prognostic factor in metastatic gastric or gastroesophageal junction cancer (mGC/GEJC). In the phase III TAGS study, trifluridine/tipiracil improved survival versus placebo in third- or later-line mGC/GEJC. These retrospective analyses examined the association of early BWL with survival outcomes in TAGS.
METHODS
Efficacy and safety were assessed in patients who experienced < 3% or ≥ 3% BWL from treatment start until day 1 of cycle 2 (early BWL). The effect of early BWL on overall survival (OS) was assessed by univariate and multivariate analyses.
RESULTS
Body weight data were available for 451 of 507 (89%) patients in TAGS. In the trifluridine/tipiracil and placebo arms, respectively, 74% (224/304) and 65% (95/147) experienced < 3% BWL, whereas 26% (80/304) and 35% (52/147) experienced ≥ 3% BWL at cycle 1 end. Median OS was longer in < 3% BWL versus ≥ 3% BWL subgroups (6.5 vs 4.9 months for trifluridine/tipiracil; 6.0 vs 2.5 months for placebo). In univariate analyses, an unadjusted HR of 0.58 (95% CI, 0.46-0.73) for the < 3% vs ≥ 3% BWL subgroup indicated a strong prognostic effect of early BWL. Multivariate analyses confirmed early BWL as both prognostic (P < 0.0001) and predictive (interaction P = 0.0003) for OS. Similar results were obtained for progression-free survival. Any-cause grade ≥ 3 adverse events were reported in 77% and 82% of trifluridine/tipiracil-treated and 45% and 67% of placebo-treated patients with < 3% and ≥ 3% BWL, respectively.
CONCLUSIONS
In TAGS, early BWL was a strong negative prognostic factor for OS in patients with mGC/GEJC receiving third- or later-line treatment.
Topics: Humans; Trifluridine; Prognosis; Uracil; Stomach Neoplasms; Retrospective Studies; Colorectal Neoplasms; Drug Combinations; Antineoplastic Combined Chemotherapy Protocols; Weight Loss
PubMed: 37106214
DOI: 10.1007/s10120-023-01393-2 -
BMC Cancer Oct 2023Inflammatory, immune, and nutritional status are key factors in obstructive colorectal cancer (OCRC). This study aims to investigate the value of modified Naples...
BACKGROUND
Inflammatory, immune, and nutritional status are key factors in obstructive colorectal cancer (OCRC). This study aims to investigate the value of modified Naples prognostic score (M-NPS) in evaluating OCRC prognosis.
METHODS
A total of 196 OCRC patients were retrospectively analyzed to construct M-NPS based on serum albumin (ALB), total cholesterol (CHOL), neutrophil:lymphocyte ratio (NLR), and lymphocyte:monocyte ratio (LMR), and then they were divided into three groups. The Kaplan-Meier (KM) method and Cox proportional hazard regression analysis were performed for overall survival (OS) and disease-free survival (DFS) of OCRC patients.
RESULTS
Patients with high M-NPS had worse OS and DFS (P = 0.0001, P = 0.0011). Multivariate COX analysis showed that M-NPS was an independent prognostic factor for OCRC patients. Patients in the M-NPS 2 group had significantly worse OS (hazard ratio [HR] = 4.930 (95% confidence interval [95% CI], 2.217-10.964), P < 0.001) and DFS (HR = 3.508 (95% CI, 1.691-7.277), P < 0.001) than those in the 0 group.
CONCLUSION
M-NPS was an independent prognostic factor for OCRC patients; it might provide a potential reference for immunonutritional intervention in patients with obstruction.
Topics: Humans; Prognosis; Retrospective Studies; Lymphocytes; Disease-Free Survival; Colorectal Neoplasms
PubMed: 37798689
DOI: 10.1186/s12885-023-11435-8 -
Journal of Cachexia, Sarcopenia and... Dec 2023Sarcopenia has been considered an adverse prognostic factor in cancer patients. Intramuscular adipose tissue content, as a new marker of sarcopenia, can effectively... (Meta-Analysis)
Meta-Analysis Review
Sarcopenia has been considered an adverse prognostic factor in cancer patients. Intramuscular adipose tissue content, as a new marker of sarcopenia, can effectively reflect skeletal muscle quality. The aim of this study was performed to evaluate the association between high intramuscular adipose tissue content (IMAC) and survival outcomes and postoperative complications in cancer patients. Specific databases, including the Web of Science, Embase and Web of Science, were systematically searched to identify relevant articles evaluating the prognostic value of IMAC in cancer patients. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were utilized for comprehensive analysis. All data analyses were performed using STATA 12.0 software. A total of 25 studies from 24 articles including 5663 patients were enrolled in the study. Meta-analysis showed that high IMAC was associated with unfavourable overall survival (OS) (HR: 2.21, 95% CI: 1.70-2.86, P < 0.001), relapse-free survival (RFS) (HR: 1.51, 95% CI: 1.30-1.75, P < 0.001) and disease-specific survival (DSS) (HR: 1.64, 95% CI: 1.19-2.28, P = 0.003). Subgroup analysis revealed that high IMAC remained an adverse prognostic factor when stratified by different country, treatment methods, cancer type or analysis type. High IMAC had better predictive value for gallbladder carcinoma (GBC) (HR: 3.50, 95% CI: 1.98-6.17, P < 0.001), hepatocellular carcinoma (HCC) (HR: 1.84, 95% CI: 1.45-2.33, P < 0.001), pancreatic cancer (PC) (HR: 2.11, 95% CI: 1.67-2.66, P < 0.001) and colorectal cancer (CRC) (HR: 2.54, 95% CI: 1.27-5.10, P = 0.009). High IMAC was also identified as a significant risk factor for postoperative complications (OR: 2.05, 95% CI: 1.22-3.46, P = 0.007). High IMAC was associated with an adverse prognosis and an increased risk of postoperative complications in cancer patients. IMAC may be a good indicator of sarcopenia.
Topics: Humans; Carcinoma, Hepatocellular; Sarcopenia; Liver Neoplasms; Retrospective Studies; Prognosis; Adipose Tissue; Postoperative Complications
PubMed: 37990969
DOI: 10.1002/jcsm.13371 -
Scientific Reports Oct 2023Glioma is the most common primary malignant tumor in the central nervous system. Disulfidptosis is a recently identified programmed cell death in tumor cells...
Glioma is the most common primary malignant tumor in the central nervous system. Disulfidptosis is a recently identified programmed cell death in tumor cells overexpressing SLC7A11 under glucose starvation. Clinical prognostic significance of disulfidptosis has been reported in several tumors, and in this study, we explored the correlation of disulfidptosis with clinical prognosis, immune cell infiltration, and immunotherapy response in glioma. A total of 1592 glioma patients were included in this study, including 691 glioma patients from The Cancer Genomic Atlas (TCGA), 300 patients with from the Chinese Glioma Genomic Atlas (CGGA) array, 325 patients from CGGA sequencing, and 276 patients from Gene Expression Omnibus (GEO) GSE16011. R software (V4.2.2) and several R packages were applied to develop the risk score model and correlation calculation and visualization. Three disulfidptosis-related genes, LRPPRC, RPN1, and GYS1, were screened out and applied to establish the risk score model. Low-risk patients exhibit favorable prognosis, and the disulfidptosis-related signature significantly correlated with clinicopathological properties, molecular subtypes, and immunosuppressive microenvironment of glioma patients. We developed a disulfidptosis-related risk model to predict the prognosis and immune features in glioma patients, and this risk model may be applied as an independent prognostic factor for glioma.
Topics: Humans; Glioma; Central Nervous System; Chromosome Mapping; Prognosis; Apoptosis; Tumor Microenvironment
PubMed: 37864127
DOI: 10.1038/s41598-023-45295-w