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International Journal of Molecular... Oct 2023Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a poor prognosis. Increasing evidence highlights the significant role of immune-related genes (IRGs)...
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a poor prognosis. Increasing evidence highlights the significant role of immune-related genes (IRGs) in ACC progression and immunotherapy, but the research is still limited. Based on the Cancer Genome Atlas (TCGA) database, immune-related molecular subtypes were identified by unsupervised consensus clustering. Univariate Cox analysis and Least Absolute Shrinkage and Selection Operator (LASSO) regression were employed to further establish immune-related gene signatures (IRGS). An evaluation of immune cell infiltration, biological function, tumor mutation burden (TMB), predicted immunotherapy response, and drug sensitivity in ACC patients was conducted to elucidate the applicative efficacy of IRGS in precision therapy. ACC patients were divided into two molecular subtypes through consistent clustering. Furthermore, the 3-gene signature (including PRKCA, LTBP1, and BIRC5) based on two molecular subtypes demonstrated consistent prognostic efficacy across the TCGA and GEO datasets and emerged as an independent prognostic factor. The low-risk group exhibited heightened immune cell infiltration, TMB, and immune checkpoint inhibitors (ICIs), associated with a favorable prognosis. Pathways associated with drug metabolism, hormone regulation, and metabolism were activated in the low-risk group. In conclusion, our findings suggest IRGS can be used as an independent prognostic biomarker, providing a foundation for shaping future ACC immunotherapy strategies.
Topics: Humans; Adrenocortical Carcinoma; Prognosis; Cluster Analysis; Databases, Factual; Adrenal Cortex Neoplasms; Tumor Microenvironment
PubMed: 37895143
DOI: 10.3390/ijms242015465 -
Frontiers in Immunology 2023During tumor growth, tumor cells interact with their tumor microenvironment (TME) resulting in the development of heterogeneous tumors that promote tumor occurrence and...
BACKGROUND
During tumor growth, tumor cells interact with their tumor microenvironment (TME) resulting in the development of heterogeneous tumors that promote tumor occurrence and progression. Recently, there has been extensive attention on TME as a possible therapeutic target for cancers. However, an accurate TME-related prediction model is urgently needed to aid in the assessment of patients' prognoses and therapeutic value, and to assist in clinical decision-making. As such, this study aimed to develop and validate a new prognostic model based on TME-associated genes for BC patients.
METHODS
Transcriptome data and clinical information for BC patients were extracted from The Cancer Genome Atlas (TCGA) database. Gene Expression Omnibus (GEO) and IMvigor210 databases, along with the MSigDB, were utilized to identify genes associated with TMEs (TMRGs). A consensus clustering approach was used to identify molecular clusters associated with TMEs. LASSO Cox regression analysis was conducted to establish a prognostic TMRG-related signature, with verifications being successfully conducted internally and externally. Gene ontology (GO), KEGG, and single-sample gene set enrichment analyses (ssGSEA) were performed to investigate the underlying mechanisms. The potential response to ICB therapy was estimated using the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and Immunophenoscore (IPS). Additionally, it was found that the expression level of certain genes in the model was significantly correlated with objective responses to anti-PD-1 or anti-PD-L1 treatment in the IMvigor210, GSE111636, GSE176307, or Truce01 (registration number NCT04730219) cohorts. Finally, real-time PCR validation was performed on 10 paired tissue samples, and cytological experiments were also conducted on BC cell lines.
RESULTS
In BC patients, 133 genes differentially expressed that were associated with prognosis in TME. Consensus clustering analysis revealed three distinct clinicopathological characteristics and survival outcomes. A novel prognostic model based on nine TMRGs (including C3orf62, DPYSL2, GZMA, SERPINB3, RHCG, PTPRR, STMN3, TMPRSS4, COMP) was identified, and a TMEscore for OS prediction was constructed, with its reliable predictive performance in BC patients being validated. MultiCox analysis showed that the risk score was an independent prognostic factor. A nomogram was developed to facilitate the clinical viability of TMEscore. Based on GO and KEGG enrichment analyses, biological processes related to ECM and collagen binding were significantly enriched among high-risk individuals. In addition, the low-risk group, characterized by a higher number of infiltrating CD8+ T cells and a lower burden of tumor mutations, demonstrated a longer survival time. Our study also found that TMEscore correlated with drug susceptibility, immune cell infiltration, and the prediction of immunotherapy efficacy. Lastly, we identified SERPINB3 as significantly promoting BC cells migration and invasion through differential expression validation and phenotypic experiments.
CONCLUSION
Our study developed a prognostic model based on nine TMRGs that accurately and stably predicted survival, guiding individual treatment for patients with BC, and providing new therapeutic strategies for the disease.
Topics: Humans; Tumor Microenvironment; Urinary Bladder Neoplasms; Prognosis; Nomograms; Immunotherapy
PubMed: 37965307
DOI: 10.3389/fimmu.2023.1213947 -
International Journal of Gynecological... Nov 2023Lymphovascular space invasion (LVSI) is a known prognostic factor for oncological outcome in endometrial cancer patients. However, little is known about the prognostic...
OBJECTIVE
Lymphovascular space invasion (LVSI) is a known prognostic factor for oncological outcome in endometrial cancer patients. However, little is known about the prognostic value of LVSI among the different molecular subgroups. The aim of this study was to determine the prognostic dependence of LVSI from the molecular signature.
METHODS
This study included endometrial cancer patients who underwent primary surgical treatment between February 2004 and February 2016 at the Karolinska University Hospital, Sweden and the Bern University Hospital, Switzerland (KImBer cohort). All cases had complete molecular analysis performed on the primary tumor according to the WHO Classification of Tumors, 5th edition. LVSI was reviewed by reference pathologists for all pathology slides.
RESULTS
A total of 589 endometrial cancer patients were included in this study, consisting of 40 mut (polymerase epsilon ultramutated), 198 MMRd (mismatch repair deficient), 83 p53abn (p53 abnormal), and 268 NSMP (non-specific molecular profile) cases. Altogether, 17% of tumors showed LVSI: 25% of the mut, 19% of the MMRd, 30% of the p53abn, and 10% of the NSMP cases. There was a significant correlation of LVSI with lymph node metastasis in the entire study cohort (p<0.001), remaining significant in the MMRd (p=0.020), p53abn (p<0.001), and NSMP (p<0.001) subgroups. Mean follow-up was 89 months (95% CI 86 to 93). The presence of LVSI significantly decreased recurrence-free survival among patients with MMRd, p53abn, and NSMP endometrial cancer, and overall survival in patients with p53abn and NSMP tumors. In patients with NSMP endometrial cancer, evidence of substantial LVSI remained a significant independent predictor of recurrence in multivariable Cox regression analysis including tumor stage and grade (HR 7.5, 95% CI 2.2 to 25.5, p=o.001).
CONCLUSION
The presence of LVSI was associated with recurrence in each subgroup of patients with MMRd, p53abn, and NSMP endometrial cancer, and LVSI remained an independent predictor of recurrence in NSMP endometrial cancer patients.
Topics: Female; Humans; Prognosis; Endometrial Neoplasms; Lymphatic Metastasis; Sweden; Retrospective Studies
PubMed: 37666529
DOI: 10.1136/ijgc-2023-004606 -
The American Journal of Surgical... Oct 2023The extent of tumor spread influences on the clinical outcome, and which determine T stage of colorectal cancer. However, pathologic discrimination between pT3 and pT4a...
The extent of tumor spread influences on the clinical outcome, and which determine T stage of colorectal cancer. However, pathologic discrimination between pT3 and pT4a in the eighth edition of the American Joint Committee on Cancer (AJCC)-TNM stage is subjective, and more objective discrimination method for deeply invasive advanced colon cancer is mandatory for standardized patient management. Peritoneal elastic laminal invasion (ELI) detected using elastic staining may increase the objective discrimination of deeply invasive advanced colon cancer. In this study, we constructed ELI study group to investigate feasibility, objectivity, and prognostic utility of ELI. Furthermore, pT classification using ELI was investigated based on these data. At first, concordance study investigated objectivity using 60 pT3 and pT4a colon cancers. Simultaneously, a multi-institutional retrospective study was performed to assess ELI's prognostic utility in 1202 colon cancer cases from 6 institutions. In the concordance study, objectivity, represented by κ, was higher in the ELI assessment than in pT classification. In the multi-institutional retrospective study, elastic staining revealed that ELI was a strong prognostic factor. The clinical outcome of pT3 cases with ELI was significantly and consistently worse than that of those without ELI. pT classification into pT3 without ELI, pT3 with ELI, and pT4a was an independent prognostic factor. In this study, we revealed that ELI is an objective method for discriminating deeply invasive advanced colon cancer. Based on its feasibility, objectivity, and prognostic utility, ELI can subdivide pT3 lesions into pT3a (without ELI) and pT3b (with ELI).
Topics: Humans; Colonic Neoplasms; Neoplasm Invasiveness; Neoplasm Staging; Prognosis; Retrospective Studies
PubMed: 37395605
DOI: 10.1097/PAS.0000000000002090 -
Aging Aug 2023Glioblastoma (GBM) is the most malignant and prevalent primary brain tumor. In this study, weighted gene coexpression network analysis (WGCNA) was performed to analyze...
Glioblastoma (GBM) is the most malignant and prevalent primary brain tumor. In this study, weighted gene coexpression network analysis (WGCNA) was performed to analyze RNA binding protein (RBP) expression data from The Cancer Genome Atlas (TCGA) for the IDH-wild type GBM cohort. The CIBERSORT algorithm quantified the cellular composition of immune cells and was used to identify key modules associated with CD8+ T cell infiltration. Coexpression networks analysis and protein-protein interaction (PPI) network analysis was used to filter out central RBP genes. Eleven RBP genes, including MYEF2, MAPT, NOVA1, MAP2, TUBB2B, CDH10, TTYH1, PTPRZ1, SOX2, NOVA2 and SCG3, were identified as candidate CD8+ T cell infiltration-associated central genes. A Cox proportional hazards regression model and Kaplan-Meier analysis were applied to identify candidate biomarkers. MYEF2 was selected as a prognostic biomarker based on the results of prognostic analysis. Flow Cytometric Analysis indicated that MYEF2 expression was negatively correlated with dysfunctional CD8+ T cell markers. Kaplan-Meier survival analysis (based on IHC staining) revealed that GBM patients with elevated MYEF2 expression have a better prognosis. Knockdown of MYEF2 in GBM cells via assays was observed to promote cell proliferation and migration. Our study suggests that MYEF2 expression negatively correlates with T cell exhaustion and tumor progression, rendering it a potentially valuable prognostic biomarker for GBM.
Topics: Humans; Glioblastoma; Prognosis; Algorithms; CD3 Complex; CD8-Positive T-Lymphocytes; Immunologic Factors; Gene Expression Regulation, Neoplastic; Neuro-Oncological Ventral Antigen; Receptor-Like Protein Tyrosine Phosphatases, Class 5
PubMed: 37556355
DOI: 10.18632/aging.204939 -
Frontiers in Immunology 2024Aminooctylamine (ANO1) plays an oncogenic role in various cancers. However. its role in pancreatic cancer (PC) has rarely been studied. This study investigated the...
BACKGROUND
Aminooctylamine (ANO1) plays an oncogenic role in various cancers. However. its role in pancreatic cancer (PC) has rarely been studied. This study investigated the prognostic value of ANO1 and its correlation with the tumor microenvironment (TME) in PC.
METHODS
Consecutive patients with PC (n = 119) were enrolled. The expression of ANO1 in cancer cells, the expression of fibroblast activation protein (FAP) and alpha smooth muscle actin in cancer-associated fibroblasts (CAFs), and the numbers of CD8- and FOXP3-positive tumor-infiltrating lymphocytes (TILs) were evaluated using immunohistochemistry. The prognostic value of ANO1 and its correlation with CAF subgroups and TILs were analyzed. The possible mechanism of ANO1 in the TME of PC was predicted using the the Cancer Genome Atlas (TCGA) dataset.
RESULTS
The expression of AN01 was correlated with overall survival (OS) and disease-free survival. Multi-factor analysis showed that high ANO1 expression was an independent adverse prognostic factor for OS (hazard ratio, 4.137; P = 0.001). ANO1 expression was positively correlated with the expression of FAP in CAFs (P < 0.001) and negatively correlated with the number of CD8-positive TILs (P = 0.005), which was also validated by bioinformatics analysis in the TCGA dataset. Moreover, bioinformatic analysis of the TCGA dataset revealed that ANO1 may induce an immunosuppressive tumor microenvironment in pancreatic cancer in a paracrine manner.
CONCLUSION
ANO1 is a prognostic factor in patients with PC after radical resection. ANO1 may induce an immunosuppressive tumor microenvironment in PC in a paracrine manner, suggesting that ANO1 may be a novel therapeutic target.
Topics: Humans; Prognosis; Tumor Microenvironment; Pancreatic Neoplasms; Lymphocytes, Tumor-Infiltrating; Proportional Hazards Models; Anoctamin-1; Neoplasm Proteins
PubMed: 38352864
DOI: 10.3389/fimmu.2024.1341209 -
The Libyan Journal of Medicine Dec 2023As a dominant type of gastric cancer, stomach adenocarcinoma (STAD) is characterized by high morbidity and mortality rates. Anoikis factors participate in tumor...
As a dominant type of gastric cancer, stomach adenocarcinoma (STAD) is characterized by high morbidity and mortality rates. Anoikis factors participate in tumor metastasis and invasion. This study was designed to identify prognostic risk factors in anoikis-related long non-coding RNAs (lncRNAs) for STAD. First, with STAD expression datasets and anoikis-related gene sets downloaded from public databases, anoikis-related prognostic lncRNA signatures (AC091057.1, ADAMTS9.AS1, AC090825.1, AC084880.3, EMX2OS, HHIP.AS1, AC016583.2, EDIL3.DT, DIRC1, LINC01614, and AC103702.2) were screened by Cox regression to establish a prognostic risk model. Kaplan-Meier and receiver operating characteristic curves were used to evaluate the survival status of patients and verify predictive accuracy of the model. Besides, risk score could be an independent prognostic factor to assess the prognosis of STAD patients. Nomograms of the prognostic model that combined clinical information and risk score could effectively predict survival of STAD patients, as validated by calibration curve. Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses were performed for differentially expressed genes (DEGs) in high- and low-risk groups. These DEGs were related to neurotransmitter transmission, signal transmission, and endocytosis. Moreover, we analyzed immune status of different risk groups and found that STAD patients in low-risk group were more sensitive to immunotherapy. A prognostic risk assessment model for STAD using anoikis-related lncRNA genes was constructed here, which was proven to have high predictive accuracy and thus could offer a reference for prognostic evaluation and clinical treatment of STAD patients.
Topics: Humans; Prognosis; RNA, Long Noncoding; Stomach Neoplasms; Clinical Relevance; Anoikis; Adenocarcinoma; Calcium-Binding Proteins; Cell Adhesion Molecules
PubMed: 37300839
DOI: 10.1080/19932820.2023.2220153 -
Cannabis and Cannabinoid Research Oct 2023One of the major challenges in improving sepsis care is early prediction of sepsis complications. The endocannabinoid system has been intensely studied in recent years;...
One of the major challenges in improving sepsis care is early prediction of sepsis complications. The endocannabinoid system has been intensely studied in recent years; however, little is known about its role in sepsis in humans. This study aimed to assess the prognostic role of endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), as early predictors of mortality, invasive mechanical ventilation (IMV) requirement, and length of stay (LOS) in patients with sepsis. In total, 106 patients with confirmed sepsis were enrolled in this study. The patients were divided into groups according to mortality outcome (survival, =53; nonsurvival, =53), IMV requirement (IMV group, =26; non-IMV group, =80), and LOS (LOS <10 days, =59; LOS ≥10 days, =47). Patients' clinical status was assessed along with laboratory biomarkers as well as AEA and 2-AG concentration measurements early on admission to emergency units. AEA and 2-AG levels were measured by enzyme-linked immunosorbent assay (ELISA) using an ELISA processor, EtiMax 3000 (DiaSorin, Saluggia, Italy). The predictive value of AEA and 2-AG for the studied sepsis outcomes and complications was analyzed using univariate and multivariate analyses and receiver operating characteristic (ROC) curve analysis. Two endocannabinoids showed no significant difference between survivors and nonsurvivors, although an AEA concentration <7.16 μg/L predicted mortality outcome with a sensitivity of 57% (95% confidence interval [CI] 42-71) and specificity of 80% (95% CI 66-91). AEA concentrations ≤17.84 μg/L predicted LOS ≥10 days with sensitivity of 98% (95% CI 89-100) and specificity of 34% (95% CI 22-47). When analyzing IMV requirement, levels of AEA and 2-AG were significantly lower within the IMV group compared with the non-IMV group (5.94 μg/L [2.04-9.44] and 6.70 μg/L [3.50-27.04], =0.043, and 5.68 μg/L [2.30-8.60] and 9.58 μg/L [4.83-40.05], =0.002, respectively). The 2-AG showed the best performance for IMV requirement prediction, with both sensitivity and specificity of 69% (<0.001). Endocannabinoid AEA was an independent risk factor of LOS ≥10 days (odds ratio [OR] 23.59; 95% CI 3.03-183.83; =0.003) and IMV requirement in sepsis (OR 0.79; 95% CI, 0.67-0.93; =0.004). Low AEA concentration is a prognostic factor of hospital LOS longer than 10 days. Lower AEA and 2-AG concentrations obtained at the time of admission to the hospital are predictors of IMV requirement.
Topics: Humans; Endocannabinoids; Prognosis; Sepsis
PubMed: 35649233
DOI: 10.1089/can.2022.0046 -
PeerJ 2023Currently, ferritin heavy chain (FTH1) has been increasingly found to play a crucial role in cancer as a core regulator of ferroptosis, while its role of non-ferroptosis...
BACKGROUND
Currently, ferritin heavy chain (FTH1) has been increasingly found to play a crucial role in cancer as a core regulator of ferroptosis, while its role of non-ferroptosis in head and neck squamous cell carcinoma (HNSCC) is still unclear.
METHODS
Herein, we analyzed the expression level of FTH1 in HNSCC using TCGA database, and FTH1 protein in HNSCC tissues and cell lines was determined by immunohistochemistry (IHC) and western blotting, respectively. Then, its prognostic value and relationship with clinical parameters were investigated in HNSCC patients. Additionally, the biological function of FTH1 in HNSCC was explored.
RESULTS
The current study showed that FTH1 is significantly overexpressed in HNSCC tissues and related to poor prognosis and lymph node metastasis of HNSCC. FTH1 knockdown could suppress the metastasis and epithelial-mesenchymal transition (EMT) process of HNSCC.
CONCLUSION
Our findings indicate that FTH1 plays a critical role in the progression and metastasis of HNSCC and can serve as a promising prognostic factor and therapeutic target in HNSCC.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Lymphatic Metastasis; Prognosis; Apoferritins; Ferritins; Oxidoreductases
PubMed: 38025726
DOI: 10.7717/peerj.16493 -
BMC Cancer Jan 2024Glioblastoma (GBM) is the most aggressive malignant central nervous system tumor with a poor prognosis.The malignant transformation of glioma cells via...
BACKGROUND
Glioblastoma (GBM) is the most aggressive malignant central nervous system tumor with a poor prognosis.The malignant transformation of glioma cells via epithelial-mesenchymal transition (EMT) has been observed as a main obstacle for glioblastoma treatment. Epithelial membrane protein 3 (EMP3) is significantly associated with the malignancy of GBM and the prognosis of patients. Therefore, exploring the possible mechanisms by which EMP3 promotes the growth of GBM has important implications for the treatment of GBM.
METHODS
We performed enrichment and correlation analysis in 5 single-cell RNA sequencing datasets. Differential expression of EMP3 in gliomas, Kaplan-Meier survival curves, diagnostic accuracy and prognostic prediction were analyzed by bioinformatics in the China Glioma Genome Atlas (CGGA) database and The Cancer Genome Atlas (TCGA) database. EMP3-silenced U87 and U251 cell lines were obtained by transient transfection with siRNA. The effect of EMP3 on glioblastoma proliferation was examined using the CCK-8 assay. Transwell migration assay and wound healing assay were used to assess the effect of EMP3 on glioblastoma migration. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were used to detect the mRNA and protein expression levels of EMT-related transcription factors and mesenchymal markers.
RESULTS
EMP3 is a EMT associated gene in multiple types of malignant cancer and in high-grade glioblastoma. EMP3 is enriched in high-grade gliomas and isocitrate dehydrogenase (IDH) wild-type gliomas.EMP3 can be used as a specific biomarker for diagnosing glioma patients. It is also an independent prognostic factor for glioma patients' overall survival (OS). In addition, silencing EMP3 reduces the proliferation and migration of glioblastoma cells. Mechanistically, EMP3 enhances the malignant potential of tumor cells by promoting EMT.
CONCLUSION
EMP3 promotes the proliferation and migration of GBM cells, and the mechanism may be related to EMP3 promoting the EMT process in GBM; EMP3 may be an independent prognostic factor in GBM.
Topics: Humans; Glioblastoma; Prognosis; Brain Neoplasms; Glioma; Epithelial-Mesenchymal Transition; Membrane Glycoproteins
PubMed: 38229014
DOI: 10.1186/s12885-023-11796-0