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Frontiers in Immunology 2023Uveal melanoma (UM) is a rare yet deadly tumor. It is known for its high metastatic potential, which makes it one of the most aggressive and lethal cancers. Recently,...
INTRODUCTION
Uveal melanoma (UM) is a rare yet deadly tumor. It is known for its high metastatic potential, which makes it one of the most aggressive and lethal cancers. Recently, immune checkpoints such as Programmed cell Death protein-1 (PD1) and Cytotoxic T-Lymphocyte-Associated significantly increasing patient survival in multiple human cancers, especially cutaneous melanoma. However, patients with UMs were excluded from these studies because of their molecular characteristics, which tend to be widely different from those of cutaneous melanoma. This study aimed to analyze the expression of V domain Ig Suppressor T-cell Activation (VISTA), a novel immune checkpoint, to evaluate its prognosis significance and its correlation with PD1 and CTLA-4.
METHODS
Evaluation of VISTA, CTLA-4, and PD1 expression was performed through TCGA database analysis and immunohistochemistry using two independent cohorts with primary malignant UM.
RESULTS AND DISCUSSION
Our results showed that VISTA expression was associated with tumor aggressiveness, T cell exhaustion, and the shortest median overall survival among patients. Surprisingly, PD1 protein expression was negative in all patients, whereas CTLA-4 expression was high in patients with advanced stages. Our findings suggest that VISTA may be a prognostic marker and an attractive treatment strategy for immunotherapy in patients with UM. Exploring its expression profile may predict response to immunotherapy and may lead to the improvement of precision therapy in malignant uveal melanoma patients.
Topics: Humans; CTLA-4 Antigen; Immunoglobulin G; Melanoma; Prognosis; Skin Neoplasms; B7 Antigens; Melanoma, Cutaneous Malignant
PubMed: 37662962
DOI: 10.3389/fimmu.2023.1225140 -
BJOG : An International Journal of... Jul 2023Cervical length is widely used to assess a woman's risk of spontaneous preterm birth (SPTB). (Review)
Review
BACKGROUND
Cervical length is widely used to assess a woman's risk of spontaneous preterm birth (SPTB).
OBJECTIVES
To summarise and critically appraise the evidence from systematic reviews on the prognostic capacity of transvaginal sonographic cervical length in the second trimester in asymptomatic women with singleton or twin pregnancy.
SEARCH STRATEGY
Searches were performed in Medline, Embase, CINAHL and grey literature from 1 January 1995 to 6 July 2021, including keywords 'cervical length', 'preterm birth', 'obstetric labour, premature', 'review' and others, without language restriction.
SELECTION CRITERIA
We included systematic reviews including women who did not receive treatments to reduce SPTB risk.
DATA COLLECTION AND ANALYSIS
From 2472 articles, 14 systematic reviews were included. Summary statistics were independently extracted by two reviewers, tabulated and analysed descriptively. The ROBIS tool was used to evaluate risk of bias of included systematic reviews.
MAIN RESULTS
Twelve reviews performed meta-analyses: two were reported as systematic reviews of prognostic factor studies, ten used diagnostic test accuracy methodology. Ten systematic reviews were at high or unclear risk of bias. Meta-analyses reported up to 80 combinations of cervical length, gestational age at measurement and definition of preterm birth. Cervical length was consistently associated with SPTB, with a likelihood ratio for a positive test of 1.70-142.
CONCLUSIONS
The ability of cervical length to predict SPTB is a prognostic research question; systematic reviews typically analysed diagnostic test accuracy. Individual participant data meta-analysis using prognostic factor research methods is recommended to better quantify how well transvaginal ultrasonographic cervical length can predict SPTB.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Cervical Length Measurement; Cervix Uteri; Pregnancy Trimester, Second; Pregnancy, Twin; Premature Birth; Prognosis
PubMed: 36871557
DOI: 10.1111/1471-0528.17443 -
International Journal of Molecular... May 2024Chemokines orchestrate many aspects of tumorigenic processes such as angiogenesis, apoptosis and metastatic spread, and related receptors are expressed on tumor cells as... (Meta-Analysis)
Meta-Analysis Review
Chemokines orchestrate many aspects of tumorigenic processes such as angiogenesis, apoptosis and metastatic spread, and related receptors are expressed on tumor cells as well as on inflammatory cells (e.g., tumor-infiltrating T cells, TILs) in the tumor microenvironment. Expressional changes of chemokines and their receptors in solid cancers are common and well known, especially in affecting colorectal cancer patient outcomes. Therefore, the aim of this current systematic review and meta-analysis was to classify chemokines as a prognostic biomarker in colorectal cancer patients. A systematic literature search was conducted in PubMed, CENTRAL and Web of Science. Information on the chemokine expression of 25 chemokines in colorectal cancer tissue and survival data of the patients were investigated. The hazard ratio of overall survival and disease-free survival with chemokine expression was examined. The risk of bias was analyzed using Quality in Prognosis Studies. Random effects meta-analysis was performed to determine the impact on overall respectively disease survival. For this purpose, the pooled hazard ratios (HR) and their 95% confidence intervals (CI) were used for calculation. Twenty-five chemokines were included, and the search revealed 5556 publications. A total of thirty-one publications were included in this systematic review and meta-analysis. Overexpression of chemokine receptor CXCR4 was associated with both a significantly reduced overall survival (HR = 2.70, 95%-CI: 1.57 to 4.66, = 0.0003) as well as disease-free survival (HR = 2.68, 95%-CI: 1.41 to 5.08, = 0.0026). All other chemokines showed either heterogeneous results or few studies were available. The overall risk of bias for CXCR4 was rated low. At the current level of evidence, this study demonstrates that CXCR4 overexpression in patients with colorectal cancer is associated with a significantly diminished overall as well as disease-free survival. Summed up, this systematic review and meta-analysis reveals CXCR4 as a promising prognostic biomarker. Nevertheless, more evidence is needed to evaluate CXCR4 and its antagonists serving as new therapeutic targets.
Topics: Humans; Colorectal Neoplasms; Prognosis; Biomarkers, Tumor; Chemokines; Receptors, CXCR4; Disease-Free Survival
PubMed: 38791414
DOI: 10.3390/ijms25105374 -
Annals of Hematology Jul 2023This prospective study aimed to investigate the prognostic effect of sarcopenia, geriatric, and nutritional status in older patients with diffuse large B-cell lymphoma...
Prognostic relevance of sarcopenia, geriatric, and nutritional assessments in older patients with diffuse large B-cell lymphoma: results of a multicentric prospective cohort study.
This prospective study aimed to investigate the prognostic effect of sarcopenia, geriatric, and nutritional status in older patients with diffuse large B-cell lymphoma (DLBCL). Ninety-five patients with DLBCL older than 70 years who were treated with immunochemotherapy were included. The lumbar L3 skeletal muscle index (L3-SMI) was measured by computed tomography at baseline, and sarcopenia was defined as low L3-SMI. Geriatric assessment included G8 score, CIRS-G scale, Timed Up and Go test, and instrumental activity of daily living. Nutritional status was assessed using the Mini Nutritional Assessment and the body mass index, and several scores used in the literature incorporating nutritional and inflammatory biomarkers, namely the Nutritional and inflammatory status (NIS), Geriatric Nutritional Risk Index, Prognostic Nutritional Index, and Glasgow Prognostic Score.Fifty-three patients were considered sarcopenic. Sarcopenic patients displayed higher levels of inflammation markers and lower levels of prealbumin than non-sarcopenic patients. Sarcopenia was associated with NIS, but was not associated with severe adverse events and treatment disruptions. They were, however, more frequent among patients with elevated NIS. Sarcopenia did not appear in this study as a prognostic factor for progression-free survival (PFS) or overall survival (OS). However, NIS emerged as predictive of the outcome with a 2-year PFS rate of 88% in the NIS ≤ 1 group and 49% in the NIS > 1 group and a significant effect in a multivariate analysis for both PFS (p = 0.049) and OS (HR = 9.61, CI 95% = [1.03-89.66], p = 0.04). Sarcopenia was not associated with adverse outcomes, but was related to NIS, which appeared to be an independent prognostic factor.
Topics: Humans; Aged; Prognosis; Nutrition Assessment; Prospective Studies; Postural Balance; Retrospective Studies; Time and Motion Studies; Sarcopenia; Lymphoma, Large B-Cell, Diffuse
PubMed: 37058153
DOI: 10.1007/s00277-023-05200-x -
Asian Journal of Surgery Sep 2023Melatonin is a neurohormone involved in diverse physiological processes, including regulation of circadian rhythm, oncogenesis and immune function. More attention are... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Melatonin is a neurohormone involved in diverse physiological processes, including regulation of circadian rhythm, oncogenesis and immune function. More attention are focused on the molecular events surrounding the occurrence of abnormally expressed lncRNAs leading to breast cancer. The purpose of this study was to evaluate the role of melatonin-related lncRNAs in the clinical management of BRCA patients and their immune responses.
METHODS
The transcriptome data and clinical data of BRCA patients were acquired from TCGA database. A total of 1103 patients were randomly assigned to either training set or validation set. A melatonin-related lncRNA signature was constructed in the training set and verified in the validation set. Functional analysis, immune microenvironment and drug resistance analysis associated to melatonin-related lncRNAs were performed by utilizing GO&KEGG, ESTIMATE and TIDE analysis. A nomogram based on the signature score and clinical characteristics was established, which was calibrated to increase prediction probability of 1-year, 3-year and 5-year survival for BRCA patients.
RESULTS
BRCA patients were divided into two signature groups based on a 17-melatonin-related lncRNA signature. High-signature patients had worse prognosis than low-signature patients (p < 0.001). Univariate and multivariate Cox regression analysis proved that the signature score was an independent prognostic factor for BRCA patients. Functional analysis indicated that high-signature BRCA involved in regulation of processing and maturation of mRNA and misfolded protein response. Remarkably, immune microenvironment analysis showed that the proportion of tumor-infiltrating M2 macrophage and the expression of CTLA4 were significantly higher in high-signature BRCA. The calibration curves for the probability of invasive BRCA showed optimal agreement between the probability as predicted by the nomogram and the actual probability.
CONCLUSIONS
A novel melatonin-related lncRNA signature was considered as an independent prognostic indicator for BRCA patients. Melatonin-related lncRNAs were potentially associated with tumor immune microenvironment and might be therapeutic targets for BRCA patients.
Topics: Humans; Female; Prognosis; Breast Neoplasms; RNA, Long Noncoding; Melatonin; Nomograms; Tumor Microenvironment
PubMed: 37330302
DOI: 10.1016/j.asjsur.2023.05.174 -
The International Journal of Biological... Dec 2023There is a lack of research evaluating the effect of tumor markers for prognosis in cervical adenocarcinoma. We aimed to develop and validate a preoperative...
OBJECTIVE
There is a lack of research evaluating the effect of tumor markers for prognosis in cervical adenocarcinoma. We aimed to develop and validate a preoperative tumor-marker-based model including clinicopathological factors to clarify the prognostic value of endocervical adenocarcinoma.
METHODS
A total of 572 patients with cervical adenocarcinoma who were staged at the International Federation of Gynecology and Obstetrics (FIGO) IA-IIA were reviewed retrospectively. Preoperative serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA)-125 and CA19-9 levels were measured. The survival and recurrence patterns were analyzed according to the tumor-marker-related stratification. The predictive values of biomarkers and clinical variables were assessed with Cox regression and competing risk models.
RESULTS
Patients with elevated preoperative tumor markers had evidently poor overall survival and recurrence-free survival. The triple-elevated tumor marker (TETM) subgroup had the worst overall survival and progression-free survival than the triple-negative tumor marker (TNTM) subgroup and the single-elevated tumor marker (SETM) subgroup. The most important predictors for overall survival were elevated tumor markers, FIGO-stage, tumor differentiation, lymphovascular space invasion (LVSI) and lymph nodes metastasis. The most important predictors for recurrence-free survival were elevated tumor markers, FIGO-stage, tumor differentiation, LVSI and deep stromal invasion. Stratified analysis showed that elevated CA-125 and CA19-9 were significantly associated with postoperative distant metastasis. A decision curve analysis confirmed that a combination of tumor markers as predictors significantly outperformed the other common predictors used (FIGO-stage, intermediate and high-risk factors, tumor differentiation, lymph nodes).
CONCLUSIONS
Elevated preoperative serum CEA, CA-125, and CA19-9 levels exhibited poor overall survival and recurrence-free survival in cervical adenocarcinoma patients. Combined preoperative serum CA-125 and CA19-9 independently predicted distant metastasis in patients with endocervical adenocarcinoma.
Topics: Female; Humans; Biomarkers, Tumor; CA-19-9 Antigen; Carcinoembryonic Antigen; Retrospective Studies; CA-125 Antigen; Prognosis; Uterine Cervical Neoplasms; Adenocarcinoma; Neoplasm Staging
PubMed: 37933442
DOI: 10.1177/03936155231206839 -
Clinical Colorectal Cancer Sep 2023Neither TP53 mutation nor DNA methylation status has been established as a biomarker alone of metastatic colorectal cancer. We analyzed the association between TP53... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Neither TP53 mutation nor DNA methylation status has been established as a biomarker alone of metastatic colorectal cancer. We analyzed the association between TP53 mutation functional subtypes and genome-wide DNA methylation status (GWMS) as combined prognostic markers.
METHODS
Patient clinical data were obtained from the TRICOLORE study, a randomized phase III trial. The TP53 mutations were classified into wild-type, gain-of-function (GOF) mutations, and non-gain-of-function (non-GOF) mutations. GWMS of the tumor tissues classified them into high-methylated colorectal cancer (HMCC) and low-methylated colorectal cancer (LMCC). Overall survival (OS) was compared based on these subgroups.
RESULTS
Of the 209 patients, 60 (28.7%) were HMCC and 149 (71.3%) were LMCC, 35 (16.7%) were TP53 wild-type and 174 (83.3%) were TP53 mutants including 79 (45.4%) GOF mutations and 95 (54.6%) non-GOF mutations. The OS of the HMCC group was shorter than that of the LMCC group (median 25.3 vs. 40.3 months, P < .001, hazard ratio 1.87) in the total cohort. The combined subgroup analyses of GWMS and TP53 mutation subtypes showed that the HMCC/GOF group had significantly shorter OS than the HMCC/non-GOF group, the LMCC/GOF group, and the LMCC/non-GOF group (median 17.7; 35.3, 40.3, and 41.2 months, P = .007, P < .001, and P < .001, respectively), regardless of the primary tumor location. By the multivariate analysis, only HMCC (P = .009) was a poor prognostic factor in the GOF mutation group.
CONCLUSIONS
TP53 GOF with HMCC is a newly identified poorest prognostic molecular subset in metastatic colorectal cancer.
Topics: Humans; Prognosis; Tumor Suppressor Protein p53; Mutation; Colorectal Neoplasms
PubMed: 37355363
DOI: 10.1016/j.clcc.2023.06.001 -
Genes Jul 2023is a copy number amplification gene that promotes tumorigenesis. However, the clinical relevance and potential mechanisms of in glioma are unclear. expression level...
is a copy number amplification gene that promotes tumorigenesis. However, the clinical relevance and potential mechanisms of in glioma are unclear. expression level data were obtained from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases, and the enriched genes and related signaling pathways were explored. Data on genes in -related signaling pathways and nine marker genes of ferroptosis were retrieved and a protein-protein interaction (PPI) network analysis was performed. The correlation of to ferroptosis and tumor infiltration of 22 kinds of human immune cells and the association between and immune checkpoint molecules were analyzed. was significantly increased in gliomas in comparison to healthy tissues. Gene Ontology (GO) and gene set enrichment analysis (GSEA) revealed the impact of expression on multiple biological processes and signaling pathways. may affect ferroptosis by interacting with genes in the cell cycle pathway and P53 pathway. The increase in was positively correlated with multiple ferroptosis suppressor genes and genes involved in tumor-infiltrating immune cells and immune checkpoint molecules in glioma. can be a new prognostic factor for glioma, which is closely related to ferroptosis, tumor immune cell infiltration, and immune checkpoint.
Topics: Humans; Ferroptosis; Immune Checkpoint Proteins; Genes, cdc; Glioma; Prognosis; Nuclear Proteins
PubMed: 37510310
DOI: 10.3390/genes14071406 -
European Journal of Medical Research Feb 2024Bladder cancer is a common malignancy of the urinary system, and the survival rate and recurrence rate of patients with muscular aggressive (MIBC) bladder cancer are not...
BACKGROUND
Bladder cancer is a common malignancy of the urinary system, and the survival rate and recurrence rate of patients with muscular aggressive (MIBC) bladder cancer are not ideal. Hypoxia is a pathological process in which cells acquire special characteristics to adapt to anoxic environment, which can directly affect the proliferation, invasion and immune response of bladder cancer cells. Understanding the exact effects of hypoxia and immune-related genes in BLCA is helpful for early assessment of the prognosis of BLCA. However, the prognostic model of BLCA based on hypoxia and immune-related genes has not been reported.
PURPOSE
Hypoxia and immune cell have important role in the prognosis of bladder cancer (BLCA). The aim of this study was to investigate whether hypoxia and immune related genes could be a novel tools to predict the overall survival and immunotherapy of BLCA patients.
METHODS
First, we downloaded transcriptomic data and clinical information of BLCA patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A combined hypoxia and immune signature was then constructed on the basis of the training cohort via least absolute shrinkage and selection operator (LASSO) analysis and validated in test cohort. Afterwards, Kaplan-Meier curves, univariate and multivariate Cox and subgroup analysis were employed to assess the accuracy of our signature. Immune cell infiltration, checkpoint and the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm were used to investigate the immune environment and immunotherapy of BLCA patients. Furthermore, we confirmed the role of TFRC in bladder cancer cell lines T24 and UMUC-3 through cell experiments.
RESULTS
A combined hypoxia and immune signature containing 8 genes were successfully established. High-risk group in both training and test cohorts had significantly poorer OS than low-risk group. Univariate and multivariate Cox analysis indicated our signature could be regarded as an independent prognostic factor. Different checkpoint was differently expressed between two groups, including CTLA4, HAVCR2, LAG3, PD-L1 and PDCD1. TIDE analysis indicated high-risk patients had poor response to immunotherapy and easier to have immune escape. The drug sensitivity analysis showed that high-risk group patients were more potentially sensitive to many drugs. Meanwhile, TFRC could inhibit the proliferation and invasion ability of T24 and UMUC-3 cells.
CONCLUSION
A combined hypoxia and immune-related gene could be a novel predictive model for OS and immunotherapy estimation of BLCA patients and TFRC could be used as a potential therapeutic target in the future.
Topics: Humans; Prognosis; Urinary Bladder Neoplasms; Immunotherapy; Algorithms; Cell Line
PubMed: 38336764
DOI: 10.1186/s40001-024-01688-9 -
Langenbeck's Archives of Surgery Sep 2023The aim of this study was to investigate the prognostic role of plasma platelet count (PLT), mean platelet volume (MPV), and the combined COP-MPV score in patients with...
OBJECTIVE
The aim of this study was to investigate the prognostic role of plasma platelet count (PLT), mean platelet volume (MPV), and the combined COP-MPV score in patients with resectable adenocarcinomas of the gastroesophageal junction.
BACKGROUND
Platelet activation, quantified by PLT and elevated MPV, plays an essential part in the biological process of carcinogenesis and metastasis. An increased preoperative COP-MPV is associated with poor survival in various tumor entities.
METHODS
Data of 265 patients undergoing surgical resection for adenocarcinoma of the gastroesophageal junction were abstracted. COP-MPV score was defined for each patient. Utilizing univariate and multivariate Cox proportional hazard analyses, survival was determined.
RESULTS
In univariate analysis, elevated PLT (HR 3.58, 95% CI 2.61-4.80, p<0.001) and increased COP-MPV (HR 0.27, 95% CI 0.17-0.42, p<0.001 and HR 0.42, 95% CI 0.29-0.60, p<0.001) significantly correlated with shorter patients' overall and disease-free survival, for all 256 patients, as well as in the subgroups of neoadjuvantly treated (p<0.001) and primarily resected patients (p<0.001). COP-MPV remained a significant prognostic factor in multivariate analysis for OS. However, PLT alone showed significant diminished OS and DFS in all subgroups (p<0.001) in univariate and multivariate analysis.
CONCLUSION
PLT is a potent independent prognostic biomarker for survival in a large prospective cohort of patients with resectable adenocarcinoma of the gastroesophageal junction. Additionally, we confirm that the COP-MPV score is significantly associated with worse outcome in these patients, but has no benefit in comparison to PLT.
Topics: Humans; Blood Platelets; Prognosis; Prospective Studies; Adenocarcinoma; Esophagogastric Junction
PubMed: 37673810
DOI: 10.1007/s00423-023-03093-y