poor overall survival
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2024 ◽  
Vol 84 ◽  
M. Ahmad ◽  
Y. Hameed ◽  
M. Khan ◽  
M Usman ◽  
A. Rehman ◽  

Abstract Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.

2022 ◽  
Vol 22 (1) ◽  
Baibei Li ◽  
Huachu Deng ◽  
Ziyan Zhou ◽  
Bo Tang

Abstract Background In recent years, the Fibrinogen to pre-albumin ratio (FPR) has been reported in many studies to be significantly associated with the prognosis of various cancers. This systematic review and meta-analysis aimed to investigate the prognostic value of FPR in malignant tumors of the digestive system based on available evidence. Methods The relevant articles published before July 1, 2021, were systematically retrieved from electronic databases to evaluate the effect of Fibrinogen to pre-albumin ratio (FPR) on the prognosis of patients with malignant digestive system tumors and calculate the hazard ratio (HR) and the corresponding 95% confidence interval (CI). Result Thirteen articles, all from China, including 15 cohort studies and a total of 5116 cases, were included in this study. A high FPR was associated with poor overall survival (HR = 1.88, 95%CI 1.53–2.32, P < 0.001), recurrence-free survival (HR = 2.29, 95%CI 1.91–2.76, P < 0.001), progression-free survival (HR = 1.96, 95%CI: 1.33–2.90, P = 0.001), complications (HR = 1.78, 95%CI: 1.06–3.00, P = 0.029), disease-free survival (HR = 1.46, 95%CI: 1.08–1.97, P = 0.013) was significantly associated with cancer-specific survival (HR = 1.44, 95%CI: 1.15–1.79, P = 0.001). Even though intergroup differences were present, FPR was strongly associated with overall and relapse-free survival, and sensitivity analysis suggested that our results were stable. Conclusion FPR can be used as a valuable indicator to predict the prognosis of patients with malignant digestive system tumors.

2022 ◽  
Zurong Zhai ◽  
Yanlin Ren ◽  
Chuanjun Shu ◽  
Dongyin Chen ◽  
Xia Liu ◽  

Abstract Background:Triple negative breast cancer (TNBC)is a type of breast cancer with poor prognosis, and still has no adequate therapeutic target and ideal medicine.The public database and the relative studies have shown that low expression of JWA is closely related to the poor overall survival in many cancers including breast cancer. However, the precise biological functions and behind mechanisms of JWA in TNBC are still unclear.Methods:Both TCGA and GEO databases were used to confirm the relationship between expression levels of JWA and overall survival inTNBC cases.JAC1, an agonisticsmall compound of JWA gene, was used in TNBC modelsin vitro and in vivo. The routine cellular and molecular assays include CCK-8, colony formation, EdUincorporation, the flow cytometry, Western blot, immunohistochemistry,immune-fluorescence microscopy and reporter gene assays were conducted in this study.Results:Low expression of JWA was associated with poor prognosis in TNBC patients. JAC1 treatment inhibited TNBCcells proliferation and promoted apoptosis in vitro and in vivo. JAC1 specifically combined and targeted YY1toeliminate its transcriptional inhibition on JWA gene.At the same time, JAC1promoted ubiquitination and degradation of YY1. The rescued JWA induced G1 phase arrest and apoptosis in TNBC cellsthrough the p38 MAPK signaling pathway. In addition, JAC1 disrupted the interaction between YY1 and HSF1, and suppressed the oncogenic role of HSF1 in TNBC throughp-Aktsignaling pathway.Conclusions:We discovered for the first time that JAC1 is a YY1 targeting compoundand maybe a potential therapeutic agent for TNBC.

2022 ◽  
Vol 13 (1) ◽  
Phyllis F. Cheung ◽  
JiaJin Yang ◽  
Rui Fang ◽  
Arianna Borgers ◽  
Kirsten Krengel ◽  

AbstractImmune evasion is indispensable for cancer initiation and progression, although its underlying mechanisms in pancreatic ductal adenocarcinoma (PDAC) are not fully known. Here, we characterize the function of tumor-derived PGRN in promoting immune evasion in primary PDAC. Tumor- but not macrophage-derived PGRN is associated with poor overall survival in PDAC. Multiplex immunohistochemistry shows low MHC class I (MHCI) expression and lack of CD8+ T cell infiltration in PGRN-high tumors. Inhibition of PGRN abrogates autophagy-dependent MHCI degradation and restores MHCI expression on PDAC cells. Antibody-based blockade of PGRN in a PDAC mouse model remarkably decelerates tumor initiation and progression. Notably, tumors expressing LCMV-gp33 as a model antigen are sensitized to gp33-TCR transgenic T cell-mediated cytotoxicity upon PGRN blockade. Overall, our study shows a crucial function of tumor-derived PGRN in regulating immunogenicity of primary PDAC.

2022 ◽  
Vol 2022 ◽  
pp. 1-13
Rongqi Li ◽  
Rongqiang Liu ◽  
Shiyang Zheng ◽  
Wenbin Liu ◽  
Hui Li ◽  

Background. Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world, and its incidence is obviously increasing. The NT5DC family has been shown to be involved in the progression of many tumors. However, the biological function of NT5DC family members in HCC is still not well understood. Methods. Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, Kaplan–Meier plotter, cBioPortal, GeneMANIA, Metascape, and TIMER were applied to assess the biological function of NT5DC family members in HCC. Results. Most of the NT5DC family members were highly expressed in HCC. High expression of NT5C2, NT5DC2, and NT5DC3 was closely associated with higher tumor stage and poor overall survival (OS). In addition, high NT5DC2 and NT5DC3 expression also predicted poor disease-free survival (DFS). Enrichment analysis revealed that the NT5DC family in HCC mainly involved the IMP metabolic process, purine ribonucleoside monophosphate metabolic process, and purine nucleoside monophosphate metabolic process. The expression of NT5DC family members was closely related to the infiltration of some immune cells, such as B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. Conclusion. Our findings provided new insights into the biological function and prognostic value of NT5DC family members in HCC.

2022 ◽  
Jingshan Liang ◽  
Changtao Liu ◽  
Dezhi Xu ◽  
Kang Xie ◽  
Aimin Li

Abstract Background: Long noncoding RNA NEAT1 has been implicated in glioma progression. However, the effect of NEAT1 on glycolysis of glioma cell and the potential mechanism remain unclear.Methods: In vitro experiments, including CCK-8, colony formation, ECAR, and lactate detection assays were performed to evaluate the effect of NEAT1 on proliferation and glycolysis of glioma cell. RNA pulldown and RIP assays were performed to identify the interaction between NEAT1 and PGK1. Truncated mutation of NEAT1 and PGK1 was used to confirm the specific interactive domains between NEAT1 and PGK1. Animal studies were performed to analyze the effect of NEAT1/PGK1 on glioma progression. Results: NEAT1 knockdown significantly suppressed the proliferation and glycolysis of glioma cells. NEAT1 could specifically interact with PGK1, which promotes PGK1 stability. Hairpin A of NEAT1 is essential for interaction with M1 domain of PGK1. Depletion of NEAT1 markedly inhibited tumor growth in mice, while PGK1 could reverse this effect. Higher expression of NEAT1 was associated with poor overall survival of GBM patients.Conclusions: NEAT1 over expression promotes glioma progression through stabilizing PGK1. NEAT1/PGK1 axis is a candidate therapeutic target for glioma treatment.

Jiabo Li ◽  
Xuya Wang ◽  
Lulu Chen ◽  
Jinhao Zhang ◽  
Yiming Zhang ◽  

AbstractGlioblastoma is the most common primary intracranial malignant tumor in adults and has high morbidity and high mortality. TMEM158 has been reported to promote the progression of solid tumors. However, its potential role in glioma is still unclear. Here, we found that TMEM158 expression in human glioma cells in the tumor core was significantly higher than that in noncancerous cells at the tumor edge using bioinformatics analysis. Cancer cells in patients with primary GBMs harbored significantly higher expression of TMEM158 than those in patients with WHO grade II or III gliomas. Interestingly, regardless of tumor grading, human glioma samples that were IDH1-wild-type (IDH1-WT) exhibited higher expression of TMEM158 than those with IDH1-mutant (IDH1-Mut). We also illustrated that TMEM158 mRNA expression was correlated with poor overall survival in glioma patients. Furthermore, we demonstrated that silencing TMEM158 inhibited the proliferation of glioma cells and that TMEM158 overexpression promoted the migration and invasion of glioma cells by stimulating the EMT process. We found that the underlying mechanism involves STAT3 activation mediating TMEM158-driven glioma progression. In vivo results further confirmed the inhibitory effect of the TMEM158 downregulation on glioma growth. Collectively, these findings further our understanding of the oncogenic function of TMEM158 in gliomas, which represents a potential therapeutic target, especially for GBMs.

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 113
Elena Genovese ◽  
Margherita Mirabile ◽  
Sebastiano Rontauroli ◽  
Stefano Sartini ◽  
Sebastian Fantini ◽  

Myelofibrosis (MF) is the Philadelphia-negative myeloproliferative neoplasm characterized by the worst prognosis and no response to conventional therapy. Driver mutations in JAK2 and CALR impact on JAK-STAT pathway activation but also on the production of reactive oxygen species (ROS). ROS play a pivotal role in inflammation-induced oxidative damage to cellular components including DNA, therefore leading to greater genomic instability and promoting cell transformation. In order to unveil the role of driver mutations in oxidative stress, we assessed ROS levels in CD34+ hematopoietic stem/progenitor cells of MF patients. Our results demonstrated that ROS production in CD34+ cells from CALR-mutated MF patients is far greater compared with patients harboring JAK2 mutation, and this leads to increased oxidative DNA damage. Moreover, CALR-mutant cells show less superoxide dismutase (SOD) antioxidant activity than JAK2-mutated ones. Here, we show that high plasma levels of total antioxidant capacity (TAC) correlate with detrimental clinical features, such as high levels of lactate dehydrogenase (LDH) and circulating CD34+ cells. Moreover, in JAK2-mutated patients, high plasma level of TAC is also associated with a poor overall survival (OS), and multivariate analysis demonstrated that high TAC classification is an independent prognostic factor allowing the identification of patients with inferior OS in both DIPSS lowest and highest categories. Altogether, our data suggest that a different capability to respond to oxidative stress can be one of the mechanisms underlying disease progression of myelofibrosis.

2022 ◽  
Vol 12 ◽  
Yang Shu ◽  
Lingling He ◽  
Meixin Gao ◽  
Fan Xiao ◽  
Junru Yang ◽  

BackgroundA preliminary study by our group revealed that the deficiency of EGF domain-specific O-linked N-acetylglucosamine transferase (EOGT) impaired regulatory T-cell differentiation in autoimmune hepatitis. Nevertheless, the prognostic value of EOGT in advanced hepatocellular carcinoma (HCC) and its relationship with immune infiltration remain obscured.MethodsInitially, EOGT expression was evaluated by Oncomine, TIMER, GEO, and UALCAN databases. Besides, the prognostic potential of EOGT expression was analyzed using GEPIA, Kaplan–Meier plotter, CPTAC, Cox regression, and nomogram in HCC samples. Furthermore, we investigated the association between EOGT expression and tumor mutation burden, DNA methylation, and immune infiltration in addition to its possible mechanism via cBioPortal, TIMER, GEPIA, ESTIMATE, CIBERSORT, GSEA, STRING, and Cytoscape.ResultsThe expression of EOGT in HCC was significantly higher than that in normal tissues. Additionally, elevated EOGT expression was correlated with advanced tumor staging and linked to poor overall survival and relapse-free survival, serving as a significant unfavorable prognostic indicator in HCC patients. Remarkably, our results revealed that high-EOGT expression subgroups with elevated TP53 or low CTNNB1 mutations have worse clinical outcomes than the others. Regarding immune infiltration, immunofluorescent staining showed that immune cells in HCC were positive for EOGT. Besides, elevated EOGT expression was linked to exhausted T cells and immune suppressor cells in HCC samples. More importantly, the proportion of CD8+ T cells was reduced in HCC samples with a high level of EOGT expression, but EOGT did not exhibit prognostic potential in HCC samples with increased CD8+ T cells.ConclusionsEOGT may hold great potential as a novel biomarker to distinguish prognosis and immune profiles of HCC patients.

2022 ◽  
Vol 12 ◽  
Yongchao Zhang ◽  
Shichao Chen ◽  
Hualei Chen ◽  
Shanshan Chen ◽  
Zhen Li ◽  

Background: Immunotherapy has shown promising therapeutic efficacy in various cancers but not gliomas. Circulating lymphocytes play critical roles in cancer control and responses to immune checkpoint inhibitors. Treatment-related lymphopenia has been associated with poor survival in patients with various tumors. This meta-analysis evaluated the risk and impact of lymphopenia in patients with glioma.Methods: The PubMed, Embase, Web of Science, and Cochrane Library databases were comprehensively searched. Eligible studies were included if they reported the incidence and risk factors of lymphopenia and the impact of lymphopenia on survival. Stata 16.0 was used for this meta-analysis.Results: A total of 21 studies were included in the final systematic review and 20 were included in the quantitative analysis. The overall incidence of grade III/IV lymphopenia was 31.6% [95% confidence interval (CI), 22.3–40.8%]. Pooled results based on pathology of glioma revealed that the incidence in astrocytoma and astrocytoma oligodendroglioma patients was 20.2% (95% CI:5.9–34.4%), and the incidence in glioblastoma patients was 27.6% (95% CI:16.2–38.9%). Lymphopenia was associated with poor overall survival (hazard ratio, 1.99; 95% CI, 1.74–2.27; P&lt; 0.001) compared to no lymphopenia. Brain receiving radiation dose of 20 or 25 Gy, female sex, older age, lower baseline lymphocyte count, and dexamethasone dose &gt; 2 mg instead of baseline use were risk factors for lymphopenia.Conclusions: Treatment-related lymphopenia was associated with decreased survival in patients with glioma. Optimization of chemoradiation regimens, particularly in patients with concurrent risk factors, can reduce lymphopenia and potentially improve survival in the era of immunotherapy.

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